Diploma Thesis

Allograft versus Allograft with Internal Bracing in Anterior Cruciate Ligament Reconstruction in Revision

Cases after ACL re-tear

Submitted by

Andrea Baltic

In partial Fulfilment of the Requirements for the Degree

Doctor of Medicine

(Dr. med. univ.)

At the

Medical University of Graz

Conducted at the

Department of Orthopaedics and Trauma

Under Supervision of

Priv.-Doz. Dr.med.univ. Gerwin A. Bernhardt, MBA and

Priv.-Doz. Dr.med.univ. Gerald Gruber, MBA Graz, 07.11.2019

i

Statutory Declaration

I hereby declare that this thesis is my own original work and that I have fully acknowledged by name all of those individuals and organizations that have contributed to the research for this thesis. Due acknowledgements have been made in the text to all other material used. Throughout this thesis and in all related publications I followed the guidelines of “Good Scientific Practice”. Graz, 07.11.2019 Andrea Baltic eh

ii

Danksagungen

Zuallererst möchte ich mich hiermit bei PD Dr. Gerwin A. Bernhardt und PD Dr. Gerald

Gruber für die Möglichkeit bedanken, bei dieser Studie mitzuarbeiten. Ein großes

Dankeschön gilt dabei Dr. Bernhardt, der mir als Ansprechperson stets zur Seite stand und

mir mit seinem Wissen und Ratschlägen von Anfang bis zum Ende immer weitergeholfen

hat. Ein weiterer Dank gilt dem Klinikvorstand der Universitätsklinik für Orthopädie und

Traumatologie Univ.-Prof. Dr. Andreas Leithner für die Möglichkeit, an der Studie

mitgearbeitet und beim internationalen SICOT Kongress in Montreal vorgestellt zu haben.

Der größte Dank gilt jedoch meinen Eltern und Geschwistern, welche schon immer an mich

geglaubt und mich in allen Lebenslagen unterstützt haben. Ohne sie wäre mein

Studienabschluss niemals möglich gewesen.

Ein großer Dank gilt auch meinen zahlreichen Freunden, von denen jeder einzelne für mein

geistiges Wohl während der langen Studienzeit gesorgt hat. Besonders erwähnen möchte ich

meine Mädels, welche seit der Schulzeit an meiner Seite stehen, sowie meine zwei

Freundinnen Sandra und Isabella, durch die die Studienzeit erst so schön geworden ist, wie

sie letztendlich war.

Meinem guten Freund Tobias möchte ich noch danke sagen, da er mir bei allem Freud und

Leid die Diplomarbeit (und auch andere Lebensereignisse) betreffend zur Seite stand und

diesen doch recht langen Weg mit mir gegangen ist.

Mein allerherzlichster Dank gilt auch meinem Freund Jan, der immer für mich da ist und

immer an mich glaubt.

Vielen Dank!

iii

Abstract

Introduction:

Anterior cruciate ligament (ACL) ruptures are one of the most common sports-associated

injuries. Increasing numbers of ACL reconstructions result in higher re-tear rates after

return-to-sport and in a higher number of revisions. Allograft transplants may be a good

alternative in complex revision cases. The use of so-called internal brace augmentation might

help graft ingrowth by providing higher primary stability. This study aimed to investigate

the outcome of patients with versus patients without internal brace augmentation in ACL

revision cases with allografts.

Material and Methods:

This is a blinded, randomized controlled pilot study with 30 patients planned. All patients

were treated with Achilles tendon allografts with bone blocks either with or without internal

brace. Data (clinical outcomes, 6- and 13-month MRI scan, SF-36, VAS, IKDC, Lysholm

Knee questionnaire, TAS and KOOS) were collected preoperatively as well as 6, 12 weeks,

6 and 13 months after surgery. Data of the 12-week follow-up results were included in this

thesis.

Results:

There were 18 patients included in the study (16,7% female). Eight patients were treated

with internal bracing (44.4%). The mean age was 29.4±7.8. There was no graft-failure in

either group. The outcome scores did not differ between the two groups after 12 weeks,

except for the IKDC being significantly better in the group without IB. The results of the

scores were KOOS 82.6±9.8, IKDC 74.7±8.8 and a median Lysholm score of 94 (65-100)

for the group without internal bracing versus KOOS 74.8±6.3, IKDC 63.9±8.7 and median

Lysholm score of 67 (62-100) in the bracing group.

Discussion:

The results show satisfactory short-term outcomes in both groups. There were no re-

ruptures or other complications in either group. There were no relevant clinical differences

between the two groups. If internal bracing might support the allograft healing process and

reduce re-ruptures has to be examined in the long term of this pilot study. Future studies then

iv

need to confirm the results in a larger cohort with adequate power and sample size

calculation.

v

Zusammenfassung

Einleitung:

Mit zunehmend steigenden Fallzahlen und guten return-to-sport Ergebnissen steigt auch die

Häufigkeit von neuerlichen Verletzungen des vorderen Kreuzbands. Die Revisionsoperation

nach einer Re-ruptur stellt jedoch häufig eine erhebliche Herausforderung für

Chirurgin/Chirurg und Patientin/Patient dar. Aufgrund der zum Teil limitierten

Entnahmemöglichkeiten von körpereigenen Sehnen sind Allografttransplantate in der

Revision von besonderem Interesse. Eine vorübergehende Fixierung (‚internal bracing‘) des

frisch transplantierten Allografts könnte durch Verminderung des Belastungsstresses zu

einer besseren Einheilung führen und somit zu einer Reduktion der Re-rupturraten.

Material und Methoden:

Bei dieser Studie handelt es sich um eine prospektiv, randomisiert, kontrollierte Pilotstudie.

Insgesamt 30 Patientinnen/Patienten wurden in eine Gruppe mit Augmentation durch

internal-bracing und ohne Augmentation randomisiert. Alle Patientinnen/Patienten wurden

mit einem Achillessehnenallograft mit Knochenblock in gleicher Operationstechnik

versorgt. Die Daten der Patientinnen/Patienten (Klinische Untersuchung, 6- und 13-Monats

MRT, SF-36, VAS, IKDC, Lysholm Knee questionnaire, TAS, KOOS) wurden präoperativ

und im Rahmen von Nachuntersuchungen (nach 6 und 12 Wochen, 6 und 13 Monaten)

prospektiv erhoben und ausgewertet. Die folgende Arbeit behandelt die 12-Wochen

Ergebnisse der ersten 18 Patientinnen/Patienten.

Ergebnisse:

Es wurden 18 Patientinnen/Patienten in die Studie eingeschlossen (16.7% weiblich). Acht

wurden mit internal bracing versorgt (44.4%). Das Durchschnittsalter der

Patientinnen/Patienten lag bei 29.4±7.8. Es gab in beiden Gruppen keine Reruptur.

Hinsichtlich des Outcomes unterscheiden sich die beiden Gruppen nach 12 Wochen nicht

signifikant, bis auf den IKDC, welcher in der Gruppe ohne internal brace signifikant besser

war. In der Gruppe ohne Internal-Brace zeigten sich 12 Wochen postoperativ für KOOS

82.6±9.8; IKDC 74.7±8.8 und im Lysholm Score 94 im Median (65-100). Die Gruppe mit

Internal-Brace zeigte mit KOOS 74.8±6.3, IKDC 63.9±8.7 und Lysholm 67 im Median (62-

100) sehr ähnliche Werte.

vi

Diskussion:

Die ersten Kurzzeitergebnisse zeigen für die verwendeten Techniken in komplizierten

Revisionssituationen in beiden Studiengruppen sehr zufriedenstellende Ergebnisse. Es gab

keine Re-rupturen oder andere Komplikationen in keiner der zwei Gruppen. Es gab auch

keine relevanten klinischen Unterschiede zwischen den beiden Gruppen. Ob das Internal-

Brace die Einheilung verbessern oder die Re-rupturraten verringern kann, kann erst nach

längerem Follow-up gesagt werden und muss in zukünftigen Studien mit größeren

Populationen evaluiert werden.

vii

Table of Contents

List of Figures ................................................................................................................. VIII

List of Tables ...................................................................................................................... X

Abbreviations .................................................................................................................... XI 1 Introduction ..................................................................................................................... 1

2 Theoretical Background.................................................................................................. 3 2.1 Anatomy of the knee joint ........................................................................................... 3

2.1.1 Bones / Articulating Surfaces............................................................................... 3 2.1.2 Menisci ................................................................................................................. 4

2.1.3 Joint Capsule ........................................................................................................ 6

2.1.4 Bursae ................................................................................................................... 7

2.1.5 Ligaments ............................................................................................................. 7 2.1.5.1 Patellar ligament ......................................................................................... 8

2.1.5.2 Fibular collateral ligament (FCL) .............................................................. 8

2.1.5.3 Tibial collateral ligament (TCL) ................................................................ 8

2.1.5.4 Oblique popliteal ligament ....................................................................... 8 2.1.5.5 Arcuate popliteal ligament ......................................................................... 8

2.1.5.6 Anterior cruciate ligament (ACL) .............................................................. 9

2.1.5.7 Posterior cruciate ligament (PCL) ............................................................ 10

2.1.6 Vascular supply and Innervation ........................................................................ 10

2.1.7 Movement .......................................................................................................... 11 2.2 Pathophysiology ........................................................................................................ 13

2.2.1 Injury mechanism ............................................................................................... 13

2.2.2 Injury Consequences .......................................................................................... 13

2.2.3 ACL Healing ...................................................................................................... 14 2.3 Risk Factors for ACL rupture ................................................................................... 15

2.3.1 Gender ................................................................................................................ 15

2.3.2 Sport ................................................................................................................... 16

2.4 Diagnostic Methods .................................................................................................. 16 2.4.1 Anamnesis .......................................................................................................... 16

2.4.2 Physical Examination ......................................................................................... 16

2.4.2.1 Lachman Test ........................................................................................... 17

2.4.2.2 Pivot Shift Test ......................................................................................... 17 2.4.2.3 Anterior Drawer Test ............................................................................... 18

2.4.2.4 Lever Sign Test ......................................................................................... 19

viii

2.4.3 Radiology ........................................................................................................... 19

2.4.3.1 Radiography ............................................................................................. 19 2.4.3.2 Magnetic Resonance Imaging (MRI) ....................................................... 20

2.5 Treatment ................................................................................................................. 21

2.5.1 Conservative Management ................................................................................. 21

2.5.2 Surgical Treatment ............................................................................................. 22 2.5.3 Alternative Treatment ........................................................................................ 23

2.6 Grafts ........................................................................................................................ 23

2.6.1 Autografts .......................................................................................................... 23

2.6.2 Allografts ........................................................................................................... 24 2.6.3 Synthetic Grafts .................................................................................................. 25

2.7 Complications .......................................................................................................... 25

2.7.1 Osteoarthritis (OA)............................................................................................. 26

2.7.2 Graft Failure ...................................................................................................... 27 2.8 Revision ................................................................................................................... 27

2.9 Rehabilitation ........................................................................................................... 28

3 Material and Methods ................................................................................................... 29 3.1 Hypothesis of the Study ........................................................................................... 29

3.2 Study Population ...................................................................................................... 30 3.2.1 Inclusion Criteria ............................................................................................... 30

3.2.2 Exclusion Criteria .............................................................................................. 30

3.3 Study Design ............................................................................................................. 31

3.3.1 General Information .......................................................................................... 31 3.3.2 Ethics ................................................................................................................. 31

3.3.3. Data Protection ................................................................................................. 32

3.3.4 Revision ACL Reconstruction Surgery ............................................................. 32

3.3.5 Allografts ........................................................................................................... 32 3.3.6 Internal Brace (Arthrex ©) ................................................................................. 33

3.3.7 Rehabilitation .................................................................................................... 34

3.4 Questionnaires .......................................................................................................... 35

3.4.1 Case Report Form (CRF) .................................................................................. 35 3.4.2 International Knee Documentation Committee (IKDC) .................................... 35

3.4.3 Knee Osteoarthritis Outcome Score (KOOS) .................................................... 35

3.4.4 Lysholm Knee Scoring Scale ............................................................................. 36

3.4.5 Tegner Activity Scale (TAS) ............................................................................ 36 3.4.6 Short Form-36 (SF-36) ...................................................................................... 36

ix

3.5 Statistical Analysis ................................................................................................... 37

3.5.1 Software Tools ...................................................................................................... 37

4 Results ............................................................................................................................. 37 4.1 Patient Demographics .............................................................................................. 38

4.2 Preoperative Data ..................................................................................................... 38

4.2.1 Physical Examination ......................................................................................... 38 4.2.2 Radiographic Evaluation .................................................................................... 39

4.2.3 Clinical Scoring Systems ................................................................................... 40

4.2.4 Short-Form 36 Health Survey ........................................................................... 40

4.3 Surgical Data ............................................................................................................ 42 4.4 12-Week-Follow-Up Data ....................................................................................... 43

4.4.1 Physical Examination ......................................................................................... 43

4.4.2 Clinical Scoring Systems ................................................................................... 43

4.4.3 Short-Form 36 Health Survey ............................................................................ 44 4.5 Case Presentation ..................................................................................................... 47

4.5.1 Patient without internal bracing ......................................................................... 47

4.5.2 Patient with internal bracing .............................................................................. 51

5 Discussion ....................................................................................................................... 54 5.1. Limitations and Strengths ....................................................................................... 57 5.2. Conclusion .............................................................................................................. 57

6 References....................................................................................................................... 58

7 Appendix – Informed Consent, Case Report Form, Questionnaires ....................... 64

x

List of Figures

Figure 1: Knee Injuries ........................................................................................................ 1

Figure 2: Ligament Injuries .................................................................................................. 2 Figure 3: Bones of the knee joint.......................................................................................... 3

Figure 4: Femoral articular surface ...................................................................................... 4

Figure 5: Tibial articular surface ......................................................................................... 4

Figure 6: Menisci .................................................................................................................. 4 Figure 7: Meniscal movements in a: extension and b: flexion ............................................. 5

Figure 8: Meniscal movements in a: neutral position, b: external rotation, and c: internal rotation .................................................................................................................................. 6

Figure 9: Joint Capsule ......................................................................................................... 6

Figure 10: Ligaments of the knee joint, a: medial view, b: lateral view .............................. 7

Figure 11: Cruciate Ligaments ............................................................................................. 9 Figure 12: Vascular supply of the knee joint ...................................................................... 10

Figure 13: Innervation of the knee joint ............................................................................. 11

Figure 14: Moving axis during flexion and extension ........................................................ 12

Figure 15: Range of motion (ROM): a: flexion and extension, b: internal and external rotation ................................................................................................................................ 12 Figure 16: Dynamic Valgus ................................................................................................ 15

Figure 17: Lachman Test .................................................................................................... 17

Figure 18: Pivot Shift Test ................................................................................................. 17

Figure 19: Anterior Drawer Test ........................................................................................ 18 Figure 20: Lever Sign Test ................................................................................................. 19

Figure 21: Frontal and sagittal radiograph of a 23-year old patient with recent ACL re-rupture, drill holes from previous ACL surgery can be seen.............................................. 20

Figure 22: Sagittal T2 weighted MRI of a 22-year old patient with recent ACL rupture .. 20

Figure 23: Unpacked Achilles Tendon Allograft ............................................................... 33

Figure 24: Finished Graft ................................................................................................... 33 Figure 25: Internal Brace integrated into the graft ............................................................. 34

Figure 26: Overview of Follow-Up Periods ....................................................................... 37

Figure 27: Preoperative ap / lateral X-ray of a patient in the group without IB ................. 39

Figure 28: Preoperative SF-36 Subscales ........................................................................... 41 Figure 29: Preoperative SF-36 Summary Scores ............................................................... 42

Figure 30: 12-Week Follow-Up Data ................................................................................. 44

Figure 31: 12-Week Follow-Up SF-36 Subscales .............................................................. 46

xi

Figure 32: 12-Week Follow-Up SF-36 Summary Scores .................................................. 46

Figure 33: SF-36 Comparison With US Normal Population .............................................. 47 Figure 34: Preoperative X-Ray Case I ................................................................................ 48

Figure 35: 6-Week Follow-Up X-Ray Case I ..................................................................... 48

Figure 36: 6-Month Follow-Up MRI Case I ...................................................................... 49

Figure 37: 13-Month Follow-Up MRI Case I .................................................................... 49 Figure 38: Preoperative X-Ray Case II .............................................................................. 51

Figure 39: 6-Week Follow-Up X-Ray Case II ................................................................... 52

Figure 40: 6-Month Follow-Up MRI Case II ..................................................................... 52

Figure 41: 13-Month Follow-Up MRI Case II ................................................................... 53

xii

List of Tables

Table 1: Muscles producing movement.............................................................................. 13

Table 2: Sensitivity and Specificity of ACL Tests ............................................................. 17 Table 3: Indications for conservative and surgical treatment of ACL ruptures ................. 21

Table 4: Advantages and disadvantages of available autografts ........................................ 23

Table 5: Advantages and disadvantages of allografts ........................................................ 25

Table 6: Complications associated with ACL reconstruction ............................................ 25 Table 7: Total patient population, total group without IB and total group with IB .......... 30

Table 8: Follow-Up Time and Performed Evaluations ...................................................... 31

Table 9: Patient demographics ........................................................................................... 38

Table 10: Preoperative Physical Examination .................................................................... 39 Table 11: Preoperative Questionnaire Data ........................................................................ 40

Table 12: Preoperative SF-36 Results ................................................................................ 40

Table 13: Surgical Data ...................................................................................................... 42

Table 14: 12-Week Physical Examination ......................................................................... 43 Table 15: Range Of Motion ................................................................................................ 43

Table 16: 12-Week Questionnaire Data ............................................................................. 44

Table 17: 12-Week Follow-Up SF-36 Results ................................................................... 45

Table 18: Questionnaire Results Case I .............................................................................. 50

Table 19: SF-36 Summary Scores Case I ........................................................................... 50 Table 20: Questionnaire Results Case II ............................................................................ 53

Table 21: SF-36 Summary Scores Case II ......................................................................... 53

xiii

Abbreviations

ACL Anterior Cruciate Ligament

AP Anterior-Posterior

AWMF The Association of the Scientific Medical Societies in Germany

BP Bodily Pain

CM Centimeter

CRF Case Report Form

FCL Fibular Collateral Ligament

GH General Health

HRQOL Health-Related Quality Of Life

IB Internal Brace

IKDC International Knee Documentation Committee

ITT Iliotibial Tract

KG Kilogram

KOOS Knee Injury and Osteoarthritis Outcome Score

LARS Ligament Advanced Reinforcement System

MAX Maximum

MH Mental Health

MIN Minimum

MM Millimeter

MRI Magnetic Resonance Imaging

MCS Mental Component Summary (SF-36)

OA Osteoarthritis

OC Oral Contraceptives

PCL Posterior Cruciate Ligament

PCS Physical Component Summary (SF-36)

PF Physical Functioning

PPI Proton Pump Inhibitor

PRP Platelet-Rich Plasma

QOL Quality of Life

RE Role Emotional

ROM Range of Motion

RP Role Physical

xiv

RR Relative Risk

RTS Return-To-Sports

SF Social Functioning

SF-36 Short Form – 36

TAS Tegner Activity Score

TCL Tibial Collateral Ligament

VAS Visual Analog Scale

VT Vitality

1

1 Introduction

Nowadays sports are a very important part of most people’s lives, despite the benefits

however, this change in western lifestyle also brings an increased rate of injuries.

Anterior cruciate ligament (ACL) ruptures are one of the most common injuries related to

sports. The ACL is involved in approximately two-thirds of all ligamentous injuries, which

make up about 40 % of all knee traumas. (1)

This also leads to an increase in ACL reconstruction surgery. Reconstruction is indicated in

patients who suffer from complex knee injuries (combination of ligament, meniscal and

chondral damages) or instability and meniscal lesions (in case of meniscal resection joint

instability increases). Likewise, patients who want to maintain their activity level and still

have athletic ambitions are considered for reconstruction. (2) These facts simultaneously

lead to an increase in additional ACL injuries after return-to-sport and therefore a higher

number of revisions. These present a particularly challenging situation for the surgeon as

they display higher complication rates than first-time reconstructions. (3) In these situations,

allografts may be a good alternative to the usually used autografts. Further muscle and tissue

damage due to tendon harvest could be avoided. In Central Europe, allografts are less

commonly used than in Anglo-American countries, similarly in primary ACL

reconstructions.

Studies comparing autografts and allografts have shown different results depending on study

design and number of patients. The majority show that autografts and allografts have no

differences in rupture rates and clinical outcomes. (4, 5) Some show that autografts display

an earlier functional recovery and lower rates of graft failure, at least compared to irradiated

allografts. (6-8) Young and active patients have the highest risk of requiring revisional

ACL47%

Complex6%

ACL + MCL12%

MCL29%

PCL4%

LCL2%

Ligament injuries

Ligament injury40%

Meniscus injury11%

Patella injury24%

Miscellaneous25%

Knee injuries

Figure 1: Knee injuries, adopted from (1) Figure 2: Ligament injuries, adopted from (1)

2

surgery. To improve allograft outcome in these cases there have been attempts to strengthen

the allogenic tissue using internal brace augmentation with a polyethylene tape which is

integrated seamlessly into the graft construct. (9) This technique was successfully used in

primary ACL repairs using the polyethylene bridging to maintain the ruptured ACL tissue.

(10)

To the best of our knowledge so far no one performed a study investigating if allografts with

additional internal bracing improve the outcome of patients compared to those using

allografts alone.

3

2 Theoretical Background

2.1 Anatomy of the knee joint The knee joint is the largest synovial joint in the human body. It allows a wide range of

motion and is composed of a complex construct of bones, muscles, soft tissue and cartilage.

(11)

2.1.1 Bones / Articulating Surfaces The knee joint is formed by three bones – the femur, tibia, and patella (the fibula is not

involved). The articulating surfaces are characterized by their incongruent shapes which

make the joint comparatively weak in a mechanical way. Therefore the stability depends on

the muscles and ligaments surrounding and strengthening the joint. (12, 13)

Figure 3: Bones of the knee joint (14)

4

Femur and tibia form the tibiofemoral joint. The proximal tibial surface (also tibial plateau)

slopes posteriorly 3 to 7° and its lateral and medial articular surfaces, which are slightly

concave, interact with the corresponding femoral condyles, which are almost completely

convex. The area between the articular surfaces of the tibia displays an eminence with medial

and lateral tubercles in the center. (14) This joint can be considered a trocho-ginglymus joint.

(16)

The second component of the knee joint is the patellofemoral joint, which is formed by the

posterior surface of the patella and the anterior surface of the femur. During flexion and

extension, the patella glides on the femoral surface, however, in full extension, only the

lowest patellar facets are in contact with the femur. (14)

2.1.2 Menisci The two menisci are C- or rather semilunar-shaped fibrocartilaginous discs that equalize the

incongruence between the femur and tibia. (11)

Figure 4: Femoral articular surface (15) Figure 5: Tibial articular surface (15)

Figure 6: Menisci (16)

5

The meniscal horns are attached to the intercondylar area of the tibia, while the peripheral

borders are fixed on the joint capsule. Sometimes there is a transversal ligament between the

two front horns of the menisci. The medial meniscus is also fixed to the medial collateral

ligament and its insertion points are further apart than those of the lateral meniscus, resulting

in it being less movable (and therefore more at risk of ruptures).

The peripheries are vascularized by capillaries from the medial knee artery, while the inner

regions are nourished through diffusion from the synovia. (11)

The menisci increase the contact area between the two corresponding bones, spreading the

load on bones and cartilage and acting as shock absorbers. In extension, the contact area is

relatively big and in the flexed knee it is rather small, allowing rotational movements. (11)

The menisci slide on the tibial surface during movement, creating a moving articular cavity,

as they follow the femoral condyles. (11, 14)

Figure 7: Meniscal movement in a: extension and b: flexion (14) Figure 7: Meniscal movement in a: extension and b: flexion (14)

6

2.1.3 Joint Capsule The joint capsule of the knee joint consists of two layers. An external fibrous capsule and an

internal synovial membrane that covers all surfaces in the cavity which are not covered with

cartilage. (11)

Figure 8: Meniscal movement in a: neutral position, b: external rotation and c:internal rotation (14) Figure 8: Meniscal movement in a: neutral position, b: external rotation, and c: internal rotation (14)

Figure 9: Joint capsule (14)

7

The fibrous layer is thickened in the front by the quadriceps tendon and the patella, and in

the back by the oblique popliteal ligament. It is fixed on the tibia 1 centimeter (cm) below

the cartilage border, and on the femur, it runs lateral of the condyles, along the intercondylar

line in the back and merges with the patella and the quadriceps tendon in the front. (11)

The synovial membrane lines the articular cavity, which contains the synovial fluid. It runs

along the anterior intercondylar area and covers the cruciate ligaments (excluded from cavity

but within the capsule). In the front, it merges into the suprapatellar bursa which extends the

joint cavity approximately 5 cm superior to the patella. Under the patella, the synovial

membrane covers the infrapatellar fat body (Hoffa’s fat pad). (11, 12)

2.1.4 Bursae There are a lot of bursae around the knee joint because most of the tendons run parallel to

the bones. (11)

The prepatellar bursae have no connection to the joint cavity and are merely there to allow

the skin to move freely during movements. There are four bursae that communicate with the

synovial cavity: suprapatellar bursa, popliteus bursa, anserine bursa, and gastrocnemius

bursa. This is important to know because an inflammation of these bursae can extend into

the cavity and cause inflammation of the whole joint. (12)

2.1.5 Ligaments There are extracapsular ligaments such as the patellar ligament, the collateral ligaments and

the oblique popliteal ligament which strengthen the joint capsule. The cruciate ligaments are

found intra-articularly. (11)

Figure 10: Ligaments of the knee joint, a: medial view, b: lateral view (14)

8

2.1.5.1 Patellar ligament

The patellar ligament is formed by the distal end of the quadriceps tendon. It is a strong,

fibrous band inserting at the tibial tuberosity. Laterally, it receives the medial and lateral

patellar retinacula (aponeurosis of the medial and lateral vastus and deep fascia) which are

part of the joint capsule and maintain the patella in place. (12)

2.1.5.2 Fibular collateral ligament (FCL)

The lateral collateral ligament extends from the lateral epicondyle of the femur to the fibular

head. It crosses the popliteal tendon which separates it from the lateral meniscus and it splits

the tendon of the biceps femoris in two parts. In connection with the short posterior genual

ligament (a lateral ligament of the joint capsule) and the TCL, it stabilizes the knee in

extension. (11, 12)

2.1.5.3 Tibial collateral ligament (TCL)

The medial collateral ligament extends from the medial epicondyle of the femur and runs

flat to the medial condyle and medial surface of the tibia. It is crossed by the tendons of the

superficial pes anserinus, separated from them by the anserine bursa. It has an anterior,

parallel running part, and a posterior fan-shaped part which is firmly attached to the medial

meniscus. The TCL is weaker than the FCL, and therefore more often damaged. (11, 12)

2.1.5.4 Oblique popliteal ligament

The oblique popliteal ligament is an expansion of the semimembranosus tendon that

reinforces the posterior joint capsule. It expends from distal medial to proximal lateral

toward the lateral femoral condyle. (12)

2.1.5.5 Arcuate popliteal ligament

This ligament also strengthens the posterior joint capsule on the lateral side. It arises from

the posterior aspect of the fibular head and forms the “short posterior genual ligament”,

which inserts at the lateral epicondyle of the femur. (see also 2.1.5.2). Sometimes it involves

a fabella, in which case it would also be known as the fabellofibular ligament. (11)

9

2.1.5.6 Anterior cruciate ligament (ACL)

The ACL is attached to the anterior intercondylar area of the tibia and ascends up to the

medial surface of the lateral medial condyle. The tibial insertion site shows a high variation,

with three possible types of shapes: elliptical (51%), triangular (33%) and C-shaped (16%).

(15) Also, there is a large difference between the tibial and femoral footprint area, the tibial

being significantly smaller. (16)

The average length and width of an ACL in adults are 38 millimeters (mm) and 11mm. (14)

Numerous studies (16, 17) showed that the ACL consists of three functional bundles: the

anteromedial, posterolateral, and intermediate bundle. Each of them playing a slightly

different role during knee movement. The posterolateral bundle is mainly stretched in

extension, and the anteromedial in flexion, especially if there is additional inner rotation.

The ligament twists around itself, the isthmus being located approximately half the distance

between the insertions and making up less than half their diameter. (18) The configuration

of the ACL two millimeters from its direct femoral insertion to mid substance is flat. (19)

The histological structures of the ACL are also particularly interesting, differencing the ACL

from other ligaments and tendons. (20) It is mostly made up of wavy collagen fiber bundles

which are arranged in various directions, most of them around the ligament axis, but also a

few running parallel to it. Also, there are fibroblasts which appear elongated in the bundle

direction. The elastic system consists of elastic and oxytalon fibers. This special

Figure 11: Cruciate ligaments (14)

10

microscopical architecture provides the ligament with the ability to withstand the multiaxial

stresses and varying tensile strains that it is exposed to. (20)

Nonetheless, the ACL is the weaker of the cruciate ligaments and more often involved in

ruptures than the PCL.(12)

2.1.5.7 Posterior cruciate ligament (PCL)

The PCL is thicker and stronger than the ACL. The average dimensions are 38 mm in length

and 13 mm in width. It expands from the lateral surface of the medial femoral condyle up to

the posterior intercondylar area and the backside of the tibia. (14)

Anterolateral and posteromedial bundles have been defined (named according to femoral

attachments). The anterolateral bundle, making up the biggest part of the PCL, tightens in

flexion while the posteromedial bundle tightens in extension. In the weight-bearing flexed

knee (for example when walking downhill) the PCL is the main stabilizer of the femur. It is

not isometric during movement as the distance between attachments varies with knee

position. (12, 14)

2.1.6 Vascular supply and Innervation The arteries supplying the knee joint

are 10 vessels forming the genicular

anastomoses: the genicular branches

of the femoral and popliteal arteries

and the anterior and posterior

branches of the anterior tibial

recurrent and circumflex fibular

arteries. The middle genicular

branches of the popliteal artery

penetrate the fibrous capsule and

supply the cruciate ligaments,

synovial membrane, and the menisci.

(12, 21)

Figure 12: Vascular supply of the knee joint (21)

11

Due to Hilton’s law (22), the nerves

innervating the muscles moving the

joint also supply the joint itself.

Therefore, the articular branches from

the femoral, tibial, and common fibular

nerves supply the knee joint.

Additionally, the obturator and

saphenous nerves also supply articular

branches to the joint’s medial aspects.

(12)

2.1.7 Movement The movements of the knee are flexion and extension, and internal and external rotation in

the flexed knee, but abduction and adduction are not possible due to the collateral ligaments.

(11)

During flexion and extension, the axis also moves, because of the complex geometry of the

articular surfaces of the femur and tibia, and the disposition of the ligaments associated

(shown in Figure 14). The motion in the medial and lateral tibiofemoral parts differ. (11)

Laterally, the displacement of the femur on the tibia is greater leading to rolling as well as

sliding on the joint surface. Medially, the motion of femur and tibia is relatively small and

shows only minimal sliding. In full flexion, the lateral femoral condyle is close to posterior

subluxation, as it comes to a stop at the edge of the tibial articular surface. (14)

Figure 13: Innervation of the knee joint (21)

12

The range of extension is 5-10° beyond the “straight position”, which can only be achieved

passively. Newborns are not able to reach the “straight position” because of the greater

retroversion of the tibia. Active flexion is approximately 120° to 140° and passive flexion

up to 160°. In the right-angled knee, an external rotation up to 40° and an inner rotation up

to 10° is possible. During inner rotation, the cruciate ligaments are twisted and tightened

around each other, and during external rotation they untangle. In reverse, the collateral

ligaments are tightened during external rotation and loosen up during internal rotation. (11)

In addition, there is also an obligatory rotational mechanism during the later stages of

extension called the “screw-home” movement. It is initiated by the tension of the ACL and

the shape of the articular surfaces and causes a 5-10° internal rotation of the femur when the

foot is standing on the ground (when the foot is not on the ground the movement is reversed

Figure 14: Moving axis during extension and flexion (created by author)

Figure 15: Range of motion (ROM) a: flexion and extension, b: internal and external rotation (14, modified from the original)

13

in terms of an external rotation of the tibia). Due to this mechanism the knee passively

“locks”, making the lower limb more stable and allowing the thigh and leg muscles to relax.

This enables us to stand for long periods without rapid exhaustion. (11, 12)

Many muscles are involved in the movements of the knee, the most important are shown in

Table 1.

Movement Primary Muscles Producing Movement Limiting Factors Extension Quadriceps femoris Anterior edge of lateral meniscus,

cruciate ligaments, collateral ligaments

Flexion Hamstrings (semitendinosus, semimembranosus, long head of biceps), short head of biceps

Soft tissue (thigh), length of hamstrings, cruciate ligaments

Internal Rotation

Semitendinosus and semimembranosus Cruciate ligaments

External Rotation

Biceps femoris Collateral ligaments, Cruciate ligaments

Table 1 : Muscles producing movement (13, 16)

2.2 Pathophysiology The ACL is a complex ligament concerning structure, function and dynamics. Analogically

multiplex are its healing process and the effects an injury has on the ligament.

2.2.1 Injury Mechanism Most ACL injuries result from a non-contact event. The injury mechanism is a flexion and

external rotation, a flexion and internal rotation, a forced external rotation or a

hyperextension movement. (23) An anterior tibial translation also significantly increases

ACL strain, therefore being a risk factor for ruptures. (24, 25) Multiplanar external forces

significantly raise loading on the ACL compared to uniplanar forces. (24, 25)

The primary internal rotation restraint from 30 to 90 degrees of flexion is not the ACL, but

the iliotibial tract (ITT). (26) Therefore, it is not surprising that damage of the ITT correlated

with functionally unstable knees and the grade of pivot shift, whereas an ACL damage did

not. For this reason, the ACL is particularly involved and at risk during rotational movements

in extension. (26)

2.2.2 Injury consequences Information about limb position and movements are brought together by visual, vestibular,

cutaneous, muscular, tendinous and joint receptors. After an ACL injury, a reduction in

14

afferent information may cause a decrease in limb function. However, visual control seems

to be more important than local receptors. When deprived of it, the remaining afferent

information is not enough for full motor performance even in healthy patients. (27)

Kinematic differences in previously injured knees show less flexed, more externally rotated

and medially translated landings. These changes in knee kinematics are believed to be the

cause of early osteoarthritic onset, which is often seen after ACL ruptures, due to joint

loading alterations. Not only do kinematic changes occur in the injured knee, but also in the

contralateral ACL-intact ones, which is believed to be on the basis of reducing the kinematic

asymmetry. (28)

2.2.3 ACL Healing The native ACL’s direct insertion shows four histological zones: ligament – uncalcified

fibrocartilage – calcified fibrocartilage – bone. This natural structure is never found in a

graft. (23)

ACL healing is a complex process and much more difficult than e.g. an MCL rupture

treatment, which usually mends spontaneously. This is probably due to the differences in

blood supply and articular environment, as well as the structural and cellular differences and

the different biomechanical demands. ACL and PCL ruptures often acquire reconstruction,

because successful healing is prohibited by lack of contact between the two ruptured ends.

(29)

After implantation, a graft processes different phases of integration: first there is acute

inflammation showing mesenchymal cell recruitment, matrix proliferation, cytokine release

and neutrophil recruitment. This is followed by a chronic phase in which fibroblasts

synthesize new extracellular matrix (tissue scar) and then a remodeling phase in which

collagen is produced and re-organized. Osteointegration between tendon and bone occurs in

six to 15 weeks after surgery and tight contact between bone and graft (for example achieved

by an interference screw) is crucial for graft integration. The process of the graft turning into

an adapted ligamentous structure appears to take place within the first three years following

reconstruction. (23)

The ACL graft develops no recognizable blood supply during the first two years of

implantation, which leads to the assumption that revascularization is not required for graft

stabilization and function, leaving synovial diffusion as the main nourishment source. (30)

However, in contrast, the periligamentous soft tissue is highly vascularized and covers the

graft. (30)

15

In summary, the success of graft integration is determined by the balance between resorption

of local blood clots, removal of cellular debris by the synovial fluid, collagen production and

growth factor expression from both, graft and host tissue. (23)

2.3 Risk Factors for ACL rupture Many genetic and lifestyle factors have been investigated with regards to a first time ACL

rupture, but only two relate to the risk of injury: gender and sport. Other risk factors such as

young age, meniscal and chondral injuries and tendon harvest are either consequential

because of other factors or not proven to have an impact. (31, 32)

2.3.1 Gender The risk of suffering an ACL injury in high-risk sports is three to six times greater for female

than for male athletes. (31, 32)

One reason for this may be the slightly different geometry seen in female knees. A decreased

femoral intercondylar notch width, decreased height of the posterior medial meniscus,

increased quadriceps angle and increased posterior tibial slope could predispose women for

ACL injuries. (32, 33)

Knee motion and loading is also a predicting factor concerning ACL injury. Landing in

inadequate flexion and increased valgus (“dynamic valgus”) and external rotation, as is often

seen in female athletes, leads to increased ACL strain and therefore higher risk of future

ACL ruptures. (31, 32)

Figure 16: Dynamic Valgus (30)

16

However, these movement biomechanics as well as lower-extremity muscle strength and

recruitment are possible to be positively adjusted applying neuromuscular training. 15

minutes of neuromuscular warm-up program twice a week significantly reduces ACL injury

rate by targeting core stability, balance, and proper knee alignment. (31, 34)

The ACL is an estrogen targeted tissue. (35) Collagen synthesis is reduced in the presence

of high estrogen levels, therefore the ligament matrix is affected. There is a protective

association between the use of oral contraceptives (OC) and the risk of sustaining an ACL

injury. However, prophylactic use of OCs to minimize injury risk in at-risk women is not

recommended until further studies have investigated the relationship between estrogen level

and ACL injuries. (35)

2.3.2 Sport ACL ruptures commonly occur during non-contact movements, usually while participating

in sports. An athlete’s risk of having a first-time ACL injury is influenced by level of

competition, gender, and type of sport. Especially knee demanding sports such as soccer,

volleyball, handball, judo etc., including stop-and-go and rotational movements during

flexion are associated with a higher injury risk. (36, 37)

2.4 Diagnostic Methods In case of an acute trauma or chronic complaints regarding the knee, there are several steps

needed to determine the right diagnosis. (2)

2.4.1 Anamnesis Asking about previous traumas or knee pathologies is essential to exclude differential

diagnoses and to distinguish acute from chronic complaints. Also, letting the patient explain

in which situations pain or instability occur, and what quality of pain is experienced, helps

gaining a lot of information before even examining the knee. Special attention should be

paid to activity level, type of sport practiced and current occupation. (2)

2.4.2 Physical Examination Diagnosing an ACL rupture based on a physical examination remains a challenge. There are

3 physical examination tests commonly used to evaluate the ACL, and a new one showing

promising results: the Lachman test, the pivot-shift test, the anterior drawer test and the

Lever sign test. (38)

17

Sensitivity Specificity

Lachman Test 81-86 % 81-94 % Pivot Shift Test 18-48 % 81-99 % Anterior Drawer Test 38-82 % 67-91 % Lever Sign Test 86-100 % 91 %

Table 2: Sensitivity and Specificity of ACL Tests (36)

2.4.2.1 Lachman Test The Lachman Test is the most valid test of the following to determine an ACL rupture. It

has a high sensitivity and specificity especially in acute injury cases and is not dependent in

other associated ligamentous or meniscal injuries being present. (39, 40)

The Lachman Test is performed by holding the knee between full extension and 15 degrees

of flexion. One hand is stabilizing the femur, while applying anterior pressure with the other

hand, holding the proximal tibia. The test is positive if an anterior translation of the tibia

with a “soft” end point is seen or felt. (40)

2.4.2.2 Pivot Shift Test Specificity of the Pivot Shift Test is very high (particularly under anesthesia), but sensitivity

rather poor. A positive Pivot Shift Test result is associated with a clinical “giving way”

symptomatology. (39, 40)

Figure 17: Lachman Test (picture taken by author)

Figure 18: Pivot Shift Test (pictures taken by author)

18

For the Pivot Shift Test, the examiner picks up the leg at the ankle and places the other hand

behind the fibula. Under a strong valgus force of the upper hand and an internal rotation of

the tibia, the knee is slowly flexed. If the ACL is torn, this position subluxates the tibia

anteriorly. At about 30 degrees of flexion the tibia suddenly reduces back to its normal

position due to tightening of the ITT. This reduction is seen and felt by patient and examiner

and indicates a positive test. (40)

2.4.2.3 Anterior Drawer Test The Anterior Drawer Test shows low sensitivity especially in acute settings. There are many

reasons for a possible false negative result:

- Due to hemarthrosis and reactive synovitis, knee flexion may be prevented.

- Joint pain may cause protective muscle action of the hamstrings which leads to an

alternate force.

- The posterior horn of the medial meniscus could be pressed against the posterior

margin of the medial femoral condyle and inhibits anterior translation of the tibia.

Also, false positive results are possible if a PCL insufficiency exists, which leads to a

posterior sagging of the tibia simulating a false neutral position. (39, 40)

For the Anterior Drawer Test the hip needs to be flexed to 45° and the knee to 90°. The

examiner sits on the patient’s foot with both hands around the proximal tibia, thumbs on the

tibial tuberosities. Then anterior force is applied. If increased tibial displacement (compared

to the other side) is seen, an ACL tear is likely.(40)

Figure 19: Anterior Drawer Test (picture taken by author)

19

2.4.2.4 Lever Sign Test The Lever Sign Test is a relatively new clinical test designed by Alessandro Lelli. The Lever

Sign Test is as sensitive as the three clinical tests presented before (2.4.2.1 – 2.4.2.3),

concerning chronic and total ACL tears. (41) But, different to the other common manual

tests, the Lever Sign Test also shows a high sensitivity regarding both acute and partial tears

of the ACL, which makes it a better alternative in these situations than the usually used

clinical tests.(41)

To perform the Lever Sign Test, a point of leverage, e.g. the examiners fist, is placed under

the supine patient’s calf and a downward force is applied on the quadriceps with the other

hand. If the ACL is intact, the patient’s heel will rise off the table, as seen in Figure 20 – a.

If the ACL is insufficient, the patient’s heel will remain on the examination table as seen in

Figure 20 – b. (41)

2.4.3 Radiology

2.4.3.1 Radiography Anterior-posterior (AP) and sagittal knee radiographs are easily available and obtained. They

are important to identify fractures or dislocations requiring emergent care. However, if only

an ACL rupture was sustained, the radiograph shows no pathologies. Nonetheless, it is an

important diagnostic tool to rule out some differential diagnosis. (42)

Figure 20: Lever Sign Test (39)

20

2.4.3.2 Magnetic Resonance Imaging (MRI) MRI is the only non-invasive diagnostic tool which can provide guaranteed certainty of an

ACL rupture and it can help to identify concomitant ligament, meniscal and/or cartilage

injuries. (42)

Figure 21: Frontal and sagittal radiograph of a 23-year old patient with recent ACL re-rupture, drill holes (white arrows) from previous ACL surgery can be seen (LKH Universitätsklinikum Graz)

Figure 22: Sagittal T2 weighted MRI of a 22-year old patient with recent ACL rupture (white arrow) (Diagnostikzentrum Graz für Computertomographie und Magnetresonanztomographie)

21

However, MRI is not only helpful with diagnosing an ACL tear, but also with verifying graft

healing after operative reconstruction. Graft volume combined with median signal intensity

of the graft, measured using MR-images, can predict clinical tests and also correlate with

common questionnaires used to analyze patient’s outcome. (43) These findings suggest, that

with the help of MRI, in combination with other follow-up methods, clinicians could better

determine the appropriate timing for patients to return to sport. (43)

2.5 Treatment There are various treatment options for ACL ruptures. The choice depends on type of injury,

patient factors, symptoms, and patient’s expectation. Some indications whether to pick a

conservative or surgical treatment are shown in Table 2. (2)

Conservative Management Surgical Treatment

• Contraindication for surgery

• Minimal knee instability

• No high activity ambitions

• Pre-existing arthrosis

• No concomitant injuries, isolated

ACL injury

• Complex concomitant injuries

(collateral ligament injuries,

meniscal injuries)

• Objective and subjective knee

instability (“giving-way”)

• Recurrent swelling

• Knee-demanding sports, activities Table 3: Indications for conservative and surgical treatment of ACL ruptures (2)

2.5.1 Conservative Management According to the current guidelines put out by the Association of the Scientific Medical

Societies in Germany (AWMF) (2), there are some individual aspects which point to

conservative management rather than surgical reconstruction. For instance, a nonsurgical

approach is suggested in patients who have other health issues making them not fit for an

operation, as well as patients who show minimal knee instability and have no high activity

ambitions. Also, pre-existing arthrosis and a lack of concomitant injuries endorses a

nonsurgical treatment. Either way, if conservative management is chosen, this does not mean

that the patient is left on their own. Muscle strengthening, physiotherapy, as well as the use

of walking aids in combination with increasing loads and clinical follow-up examinations

are essential. (2)

22

The views on conservative management of an ACL injury show broad variation, but if

patients are willing to lower their activity level, nonsurgical treatment can lead to

comparable clinical results to surgical reconstruction. (44) In moderately active patients (not

athletes), the clinical results between early or late surgically reconstructed knees or those

treated with rehabilitation alone, do not differ at all.(45, 46) The overall exception are

children and adolescents. Within this cohort, early surgical stabilization is preferred.

Nonoperative treatment in these patients results in a persistently unstable knee and therefore

further intra-articular damage. Also, the inability to return to previous activity levels,

especially in young patients, has a great impact in everyday-life. (47)

2.5.2 Surgical Treatment Surgical treatment is indicated if patients report “giving-way”-sensations in daily living or

if they want to resume knee-straining activities/sports such as football, basketball, volleyball,

tennis, and skiing. (48) Other indications can be seen in Table 2.

There is no guaranteed report of the right time for a surgical intervention after an ACL

rupture. (2) However, moderate evidence supports reconstruction within five months after

surgery, to avoid cartilage and meniscal damage. (42) The official guideline by the AWMF

favors surgery 48 hours within injury or after the acute inflammatory phase passes and ROM

is regained. (2) Early (<two weeks) and late (four to six weeks after injury) reconstruction

lead to a similar clinical and functional outcome. (49)

If surgery is not performed immediately, injury management should focus on the reduction

of hemarthrosis with rest, ice, compression, and elevation. Sometimes the administration of

nonsteroidal anti-inflammatory agents can be helpful. (48)

There is no age limitation for a surgical approach. Patients older than 40 years even achieve

comparable clinical outcomes to younger patients. (50)

ACL reconstruction is an arthroscopically performed procedure. The ruptured ACL is

replaced by a suitable graft, which is anatomically implanted in the original femoral and

tibial footprint area. (2) In children and adolescents traditional reconstruction techniques

may disrupt the growth plates, leading to leg-length discrepancies, axis disturbances or

physeal disruptions. In these cases, special procedures sparing or avoiding the physis must

be considered. (47)

23

2.5.3 Alternative Treatment Besides these two most common approaches to treat a ruptured ACL, there are also other

procedures being investigated at the moment.

Currently, there is no attempt to repair the torn ligament because isolated repair has met only

moderate success in history. (10) The main inhibitor of intrinsic ACL healing being the lack

of clot formation between the two torn ends of the ACL.(51) However, in most cases,

sufficient tissue remains for a repair to be considered. (10) Using an Internal Brace

Augmentation system to protect ACL repair may offer an advantage over previous ACL

repair techniques. (10)

On the other side, there has been growing interest on regenerative approaches to stimulate

ACL healing during procedures of reconstruction or repair, using platelet-rich plasma (PLP)

or stem cells. (52) Although some studies showed promising short-term outcomes, there is

still insufficient evidence to support the use of these biological agents systematically. (52,

53)

2.6 Grafts There are a lot of options when it comes to graft choice in ACL reconstruction. There is no

such thing as the ideal graft that fits every patient in every situation. Deciding on which graft

to use is always an individual patient (activity level, comorbidities, tissue availability, prior

surgeries, preference) and surgeon-dependent (experience, preference) choice. (54)

The ideal graft should have structural and biomechanical qualities similar to those of the

native ligament, allow secure fixation and rapid biologic incorporation, and limit donor site

morbidity. (54)

2.6.1 Autografts Autografts are most commonly used when it comes to primary ACL reconstructions.

However, there is no ‘gold standard’ graft in these procedures, as none has clearly shown a

faster return-to-sports than the other ones. (54) The individual advantages and disadvantages

of the available autograft choices can be seen in Table 3. (55)

Bone – Patellar Tendon-

Bone

+ bone-to-bone

healing in both

tunnels

- risk of anterior

kneeling pain

- invasive, large

incision

24

+ comparable stiffness

to native ACL

- risk of patellar

fracture

- fixed length

- weaker than native

ACL

Hamstring Tendon + easy to harvest

+ cosmetics

+ minimal donor site

morbidity

+ comparable strength

to native ACL

- soft tissue healing

- unpredictable graft

size

- not for athletes who

rely on their

hamstring muscles

- less stiffness than

native ACL

Quadriceps Tendon + large graft

+ option of a one-sided

bone block

- invasive, large

incision

- risk of patellar

fracture Table 4: Advantages and disadvantages of available autografts (53)

2.6.2 Allografts Another option besides autologous grafts are allografts. At first mostly used in revision or

multiple ligament rupture cases, primary use of allografts is getting more common.

Particularly when the native tissue is insufficient for repair or donor site morbidity presents

a problem, allografts are a suitable choice. (56)

Regarding the clinical outcome of allograft in comparison to reconstruction with autografts,

there is no clear opinion. A lot of studies show poorer clinical outcome and higher failure

and revision rates regarding allografts, but mostly in irradiated grafts. (57, 58) When

comparing autografts and non-irradiated allografts there is no significant difference in

results. (59)

The most often mentioned disadvantage of allografts is the commonly known inferior

remodeling and healing process. Autografts show a more advanced remodeling progress at

early stages of recovery than allografts. However, after one year both groups return to an

ACL-similar structure. (60) Despite the disadvantages, there are also a lot of positive aspects

regarding allograft use, which can be found in Table 4. (56)

25

Advantages and disadvantages of allografts

+ faster postoperative recovery

+ less postoperative pain

+ no graft harvest needed shorter surgery

time

+ no donor site morbidity

+ length and diameter available as needed

- lower stability rate

- higher graft failure rate

- slower graft incorporation

- concerns of disease transmission

Table 5: Advantages and disadvantages of allografts (54)

2.6.3 Synthetic Grafts Artificial grafts have long been under consideration as they represent a type of graft which

is easily available and would simplify the surgery as there is no preparation time involved

as in allografts or even graft harvesting as in autografts. However, most of them have showed

high failure rates in the past. (61) The new generation synthetic ‘Ligament Advanced

Reinforcement System’ (LARS) has gained more popularity than its predecessors and

showed comparable complication rates to traditional surgical techniques in short-term follow

up. (62) Nevertheless, first long-term results indicate that the LARS system should not be

considered as a potential graft for ACL reconstruction in a primary setting, because of high

failure rates and poor patient satisfaction. (63)

2.7 Complications A list of general and ACL-Reconstruction-specific complications associated with ACL

reconstruction can be found in Table 6. (64)

Complications associated with ACL reconstruction

General Complications

Vascular Damage Rare

Nerve Damage Occurs in 8.2% of arthroscopic knee

surgeries (64)

Infection Occurs in 0.8% of ACL reconstructions

(64)

26

Thrombosis and Embolism Occurs in 1.5-17.9% of arthroscopic knee

surgeries without thromboembolic

prophylaxis (64)

Osteoarthritis See 2.7.1

ACL-Reconstruction-Specific Complications

Graft Damage Not reported

Wrong Drill Hole Placement Not reported, leads to Graft Failure

Graft Failure See 2.7.2 Table 6: Complications associated with ACL reconstruction (64)

The general complications mentioned in Table 6 occur in every arthroscopic knee surgery.

Vascular damages can be avoided by properly flexing the knee while drilling the femoral

and tibial tunnels to protect the popliteal vessels. Nerve damages are one of the most

common intraoperative complications. They occur mostly during graft harvest and

arthroscopic portal incisions and result in paresthesia and dysesthesia. However, the sensory

deficit most commonly regresses a short time after the procedure. Infections occur only in

rare cases. Additional procedures such as meniscal-resection or sutures increase the risk of

intraarticular infections, as well as previous knee surgeries. An infection occurs most

commonly 3-5 days after surgery and should be treated with arthroscopic rinses,

synovectomy, debridement and intra venous antibiotics. To prevent postoperative

thrombosis and embolism, a prophylaxis using low molecular weight heparin should be

administered until full loading. (64)

An ACL reconstruction specific complication is graft damage. It occurs mostly during graft

harvest or graft fixation. The preparation and harvest of the hamstring-graft showed to be

more complicated and riskier than the patellar-tendon graft. However, harvesting of the

patellar tendon with a proximal and distal bone block can, in rare cases, lead to patella

fracture. Another cause for complications can be the drill hole placement. Wrong placement

of the femoral drill hole is considered the most common cause for reconstruction failure. In

most cases the drill hole is placed more anterior then it should, leading to graft laxity. (64)

2.7.1 Osteoarthritis (OA) OA in injured joints is caused by pathogenic processes initiated at the time of injury, and

long-term changes in biomechanical joint loading. (65) At 10 to 20 years after diagnosis,

about 50% of those with a diagnosed ACL tear have OA with associated pain and functional

impairment. (65) ACL injury predisposes to OA, while ACL reconstruction surgery reduces

the risk of developing degenerative changes. (66) The relative risk (RR) of developing OA

27

in nonoperatively treated ACL injuries is significantly higher (4.98) compared with those

treated with reconstruction (3.62). (66) However, even after reconstruction surgery, patients

with ACL injuries in the past show a three-fold increased prevalence of OA compared with

the contralateral healthy knee. (67)

2.7.2 Graft Failure Graft failure is a rare, but dreaded complication after ACL reconstruction. Estimated revision

rates vary from three to nine percent depending on source and follow-up. (68-70)

There are many possible reasons for an ACL re-tear after reconstruction. The graft may fail

as a result of traumatic overload, poor surgical technique, untreated concurrent knee injuries,

or poor biological incorporation of the graft. (69) Possible predictors of revision surgery are

young age at time of reconstruction and competitive activity level, especially in soccer

players. (70) There are no associations regarding sex, height, weight, or body mass index.

(71)

2.8 Revision Up to 20% of patients experience complications like knee laxity and/or instability during

athletic activities or daily life after primary reconstruction due to graft failure. (72) Revision

surgery is performed in order to stabilize the knee joint, prevent further cartilage and menisci

damage, and allow the patient to resume normal daily and/or sports activities. (72)

Revision surgery poses several diagnostic and technical challenges compared to primary

reconstructions. Due to the complexity of this procedure, preoperative planning is essential.

It begins with determining the cause of failure for the primary reconstruction. Furthermore,

a thorough history regarding the initial surgery, associated injuries, used graft type, fixation

method, as well as other prior procedures performed are necessary to obtain. (73)

Widening of the tibial and femoral tunnels presents a substantial obstacle during revision

surgery because of the bone loss and poor graft fixation leading to delayed graft

incorporation and decreased stability. There are many mechanical and biologic factors

responsible for tunnel widening, including graft position, fixation method, graft type, graft

donor, synovial fluid, and implant material and preparation. (74) Sometimes, a two-stage

procedure with initial tunnel bone grafting followed by ACL reconstruction four to six

months later is necessary. (73) Another solution would be the use of an allograft with large

bone block, which can be constructed and tailored to the specific deficit. (74) Radiography,

28

CT, and MRI can be used to determine the extent of widening, which should be about 10

Millimeters in diameter normally, but often exceeds 15 Millimeters. (74)

Another unique problem in revision reconstruction is preexisting hardware. Biodegradable

hardware is prone to fragmentation and cannot be removed easily. Therefore, it should be

left in place. In contrast, metal interference screws must be removed when interfering with

proper tunnel placement. (73)

The outcome of revision reconstructions is worse compared with primary reconstruction.

The failure rate is nearly three to four times higher. (3) Return-To-Sport (RTS) rates after

revision are similar to those after primary reconstruction in individual patients, but still lower

than those of patients who did not need revision surgery in the first place. (75) Patients need

to know, that a return to their previous level of performance before their first ACL

reconstruction cannot be expected. (73)

2.9 Rehabilitation Numerous factors have an impact on an optimum return to function after ACL reconstructive

surgery, one of them being the impact of external and internal forces over the course of the

postsurgical period. Precisely, the degree of joint force that rehabilitation exercises produce,

the nature of performed exercises in terms of intensity, mode, frequency, and duration; and

their impact on knee joint proprioception are very important. One cause for graft failure may

involve overloading of the reconstructed knee as a result of inappropriate dosage or

performance of various exercises. (76)

Movements applied to the knee joint postoperatively extending 30° of knee flexion increase

joint swelling, but if performed in the final degrees of extension, there is a noted decrease in

quadriceps inhibition, as well as an improved healing rate. (76)

Appropriate initiation of non-weightbearing exercises designed to reduce knee extensor

muscle atrophy is the primary goal of a lot of ACL rehabilitation programs. However,

anatomical research has shown that when the knee extensors contract, they can cause anterior

tibial displacement, especially if performed in an ‘open’ kinetic chain mode. When

performed in a ‘closed’ kinetic chain mode ACL stress is minimized and additionally, more

specific and sensory feedback is stimulated. (76)

The quantity of exercises an individual performs in a given period after ACL reconstruction

surgery similarly impacts recovery. For example, even low workload exercises can increase

the anterior laxity of both normal and ACL reconstructed knees.

29

On the other side, an inappropriate exercise dosage that results in muscle atrophy may not

only lead to knee joint instability, it also may prevent appropriate healing of the newly

constructed graft. (76)

One important factor of rehabilitation after ACL reconstruction is RTS. A return to the

preinjury level of activity is commonly assumed to take between 6 and 12 months. However,

only one third of active patients make it by this time. After two years, two out of three

patients return to their preinjury level sport. This suggests that some patients simply need

more time to recover than initially suggested. (77)

Unlike previously expected, RTS does not depend exclusively on physical function, but is

multifactorial. A lot of psychological factors like fear of reinjury or pain, recovery

expectations, and the feeling of uncontrollability during sports predict RTS outcomes. Male

and young patients are more likely to return to their previous level of sport than older patients

and women. (77)

The second important part of rehabilitation presents the Quality of Life (QOL) level after

surgery. Measured with the Short Form-36 (SF-36) ACL reconstruction resulted in a

relatively high gain of quality-adjusted life years. In the physical component summary (PCS)

score large improvements were noted at two years and maintained at six years after ACL

reconstruction, showing that physical benefits are durable throughout many years. The

mental component summary (MCS) score, as well as the general health subscale are both

well above population norm in patients undergoing ACL reconstruction and do not change

dramatically over time. (78)

3 Material and Methods

3.1 Hypothesis of the Study The hypothesis of this study was that the clinical outcome of patients with internal brace

(IB) augmentation in ACL revision cases is better than without, because of improved healing

conditions. Furthermore, we wanted to evaluate the difference in QOL and RTS.

Therefore, the study objectives were:

• Visual Analog Scale (VAS) for Pain in patients treated without and with IB

augmentation

• Knee specific clinical scores in patients treated without and with IB augmentation

• QOL in patients treated without and with IB augmentation

• RTS in patients treated without and with IB augmentation

30

3.2 Study Population

3.2.1 Inclusion Criteria All patients (n=18) who underwent ACL revision reconstruction while this study took place

at the University Hospital of Graz (Austria) and who matched following criteria were

included in the study:

• MRI verified re-tear of the ACL and

• Clinical and patient-reported instability of the knee joint and

• Signed informed consent

Table 7 gives an overview of the patients’ characteristics of the total study population.

Gender Total Without IB With IB

Patients (n)

All 18 10 8

Male 15 10 5

Female 3 0 3

Age (years, mean ± SD)

All 29.4 ± 7.8 28.2 ± 7.7 30.9 ± 8.3

Male 28.6 ± 7.4 28.2 ± 7.7 29.4 ± 7.6

Female 33.3 ± 10.5 / 33.3 ± 10.5

BMI (mean ± SD)

All 24.83 ± 2.0 25.1 ± 1.8 23.3 ± 1.8

Male 24.5 ± 2.0 25.1 ± 1.8 23.3 ± 1.9

Female 23.1 ± 2.0 / 23.1 ± 2.0 Table 7: Total patient population, total group without IB and total group with IB, SD= standard deviation

3.2.2 Exclusion Criteria Patients were excluded if they:

• suffered from an advanced stage of OA

• had an ongoing infection

• had cancer

• suffered from any immunosuppressant disease

• had a diagnosed neuromuscular disease

• suffered from a psychiatric disease, which made them unfit to consent

• had a writing and/or reading disability

• could not speak German or English and there was no interpreter available

31

3.3 Study Design

3.3.1 General Information This study was designed as a prospective, randomized pilot study starting on the 14th

February, 2017 (date of ethic votum). Various questionnaires, physical examination and

imaging evaluations at different study timepoints were planned (Table 8). We collected

general information using a self-designed Case Report Form (CRF). The data collection was

performed by the operators of the survey.

Before

Surgery

After 6

weeks

After 12

weeks

After 6

months

After 13

months

Clinical

Examination X X X X X

VAS of Pain X X X X X

IKDC X X X X X

KOOS X X X X X

Lysholm Knee

Scoring Scale X X X X X

TAS X X X X X

SF-36 X X X X X

Radiography X X X X X

MR-Imaging X X X Table 8: Follow-Up Time and Performed Evaluations

The patients were blinded and randomly categorized into two groups (with and without IB

augmentation), The surgeon and the survey staff were unblended. The study was planned as

a single-surgeon study.

30 patients have been planned to be included, 15 in each group, over the course of three

years. In this diploma thesis the patients included until 31st January, 2019 and their

preliminary results are analyzed.

3.3.2 Ethics All participants of the study had to sign an informed consent before inclusion, confirming

their approval of usage of their data. The informed consent can be found in the appendix of

this thesis (see chapter: 8. Appendix - Informed Consent, Case Report Form, Questionnaire).

32

The ethics committee of the medical university of Graz authorized this study with the project

number 29-136 ex 16/17.

3.3.3 Data Protection For this survey, protected medical information was needed: patients’ names, dates of birth,

phone numbers, addresses, operation dates, and other personal information. This data is

available in the hospital information system openMEDOCS (KAGES group).

The collected data is registered in a Microsoft Excel datasheet. The datasheet is password

protected, only members of the study staff have access to it. For the statistical analysis and

publication, patient sensitive data is anonymized.

3.3.4 Revision ACL Reconstruction Surgery We used a modified all-inside technique for our revision ACL reconstruction. (79) In

primary ACL repairs this technique shows the advantage of lower bone loss and

determination of tunnel length even before drilling. Therefore, length of the graft must not

be too long, because this would lead to increased laxity of the graft construct. (79, 80) The

femoral tunnel is drilled approximately 2 cm proximal and 1 cm anterior of the epicondylus

lateralis, stopping 1 cm before reaching the cortex. The tibial tunnel is drilled starting from

the ACL insertion point up until 40 mm before reaching the cortex. With a shuttle-thread the

graft is inserted femorally through the anteromedial portal, and then tibially. In a nearly-

extension position the graft is then tightened. (79, 81) In revision cases the tibial tunnel is

drilled from the outside and the emerging bone defect is preoperatively measured and filled

with the achilles tendon bone block. In 8 patients (44%) an additional tibial screw was used

to add stability.

3.3.5 Allografts We obtained our allografts from LifeNet Health ©, a non-profit provider of allograft bio-

implants and organs for transplantation stationed in Virgina, USA. The allografts were

imported and distributed by AlloTiss Gemeinnützige Gewebebank GmbH in Austria and

thereafter by LifeNet Health © Europe, Vienna. The actual sales process and appropriate

usage of the products is supported by Arthrex ©, a global medical device company.

LifeNet Health © uses a patented and validated washing process called Allowash XG. It

provides a Sterility Assurance Level of 10-6, while still maintaining biomechanical and

biochemical properties of the tissue. Since 1995, there has been no record of disease

transmission. The Allowash XG process ends with a controlled dose of gamma irradiation,

33

administered at low temperatures after the tissue is packaged. Studies have shown no

difference in outcomes to non-irradiated autograft tendons. (82)

In the donor screening process information like cause of death, demographics, and any

contraindications to donation such as malignancy or infectious diseases are considered. After

the organ recovery is completed, the eyes and soft tissues of the donor are recovered in a

surgical procedure that is much like any standard operation. (82) In all patients we used an

achilles tendon with bone block, available in different dimensions (see Figure 23).

Figure 23: Unpacked Achilles Tendon Allograft (image taken by author)

Bone and tendons were shaped and adapted intraoperatively, depending on the bone defect

of the previous operation using an Arthrex Graft Prep Station © (see Figure 24).

Figure 24: Finished Graft (image taken by author)

3.3.6 Internal Brace (Arthrex ©) To protect the allograft during the revascularization and remodeling phase, which was shown

to be slower than in autografts, an internal brace was added in one study group. This

polyethylene/polyester fibre tape (Arthrex ©) is integrated seamlessly into the tendon graft

construct (see Figure 25). It is tensioned and fixed independently from the graft and always

at full hyperextension so it won’t lead to an overconstraining of the joint and therefor to a

loss of motion.(9)

34

3.3.7 Rehabilitation After surgery the patients received analgetic medication in addition to PPI (proton pump

inhibitor) therapy upon need.

During the first three weeks postoperatively, patients were allowed half body weight-bearing

in combination with crutches. During this period, they received thrombembolic prophylaxis

until full weight-bearing. In the first two weeks they wore a brace locked at 0/0/30. In the

four following weeks the brace was locked at 0/0/90. During this time period patients

performed physiotherapy with passive, isometric muscle-exercises and received lymphatic

drainage. After six weeks they were allowed full weight-bearing without a brace and active

exercise guided by a physiotherapist. Particular attention was paid to increase quadriceps

strength. A return to ACL-demanding sports was advised not to take place in the first 12

months after reconstruction.

Figure 25: Internal Brace (Arrow) integrated into the graft (Arthrex ©)

35

3.4 Questionnaires

3.4.1 Case Report Form (CRF) The questions were divided into general information (gender, age, affected side, BMI,

occupation, and activity level before injury), patient’s history (pre-existing conditions,

allergies, medication, consumption of alcohol, packyears), VAS of Pain, and clinical

examination. For further information the whole questionnaire is available in the Appendix

(see chapter: 8. Appendix - Informed Consent, Case Report Form, Questionnaire)

3.4.2 International Knee Documentation Committee (IKDC) The IKDC questionnaire helps to detect improvement or worsening in symptoms, function,

and sports activities due to knee impairment. It was developed in 1997 and has undergone

several minor revisions since its publication in 2001. (83)

It is divided into three domains:

1) Symptoms, pain, stiffness, swelling, locking/catching, and giving way

2) Sports and daily activities

3) Current knee function and knee function prior to knee injury (not included in the total

score)

The total score is calculated as (sum of items) / (maximum possible score) x 100, to give a

total score of 100. The usefulness of the IKDC has been shown, as it is responsive to change

following surgical interventions. (83)

3.4.3 Knee Osteoarthritis Outcome Score (KOOS) The KOOS questionnaire is used to measure patients’ opinions about their knee and

associated problems over short- and long-term follow-up. The original KOOS remains

unchanged up to now. (83)

It consists of five domains:

1) Pain frequency and severity during functional activities

2) Symptoms such as the severity of knee stiffness and the presence of swelling,

grinding or clicking, catching, and range of motion restriction

3) Difficulty experienced during activities of daily living

4) Difficulty experienced with sport and recreational activities

5) Knee-related QOL

The score ranges from 0 to 100, 100 meaning that there are no problems present. The KOOS

appears to be responsive to change in patients with a variety of conditions that have been

treated with nonsurgical and surgical interventions. (83)

36

3.4.4 Lysholm Knee Scoring Scale The Lysholm Knee Scoring Scale was developed to evaluate outcomes of knee ligament

surgery, particularly symptoms of instability. It was first published in 1982 and revised in

1985. There are only 8 items, making up a possible score of 100. The scores are categorized

as excellent (95-100), good (84-94), fair (65-83), and poor (<63). I was reported to be very

responsive to change following ACL reconstruction. (83)

3.4.5 Tegner Activity Scale (TAS) The TAS provides a standardized method of grading work and sport activities. It was

intended for use with the Lysholm Knee Scoring Scale, in patients with ACL injury. It

contains a graduated list of activities of daily living, recreation, and competitive sports.

Patients select the level that best describes their current level of activity. The possible score

ranges from 0 to 10, levels 6 to 10 can only be achieved if the person participated in

recreational or competitive sport. (83)

3.4.6 Short Form – 36 (SF-36) The 36-Item Short Form Health Survey questionnaire is a very popular instrument used to

evaluate health-related quality of life (HRQOL). It was not developed to measure QOL in

patients with a specific disorder, but rather in order to have a generic measurement of QOL

in all patients. It was first published in 1992, and revised in 1996 when a second version was

introduced. (84) There are 36 items to be answered, which are subdivided into eight scales:

• Physical Functioning (PF)

• Role Physical (RP)

• Bodily Pain (BP)

• General Health (GH)

• Vitality (VT)

• Social Functioning (SF)

• Role Emotional (RE)

• Mental Health (MH)

These subscales are subordinate to two main scales, and contribute in different proportions

to the scoring of these:

- Physical Component Summary (PCS)

- Made up from PF, RP, BP, GH

- Mental Component Summary (MCS)

- Made up from VT, RE, SF, MH

37

The SF-36 does not provide a single measure of health-related QOL. For the analysis a

manual and an interpretation guide is needed. The calculated data can be compared with data

from an age- and sex matched normal population. (84) The whole questionnaire can be found

in the appendix of this thesis (see chapter: 8. Appendix - Informed Consent, Case Report

Form, Questionnaire).

3.5 Statistical Analysis Standard descriptive statistics (tables, diagrams, graphics, etc.) were used for the description

of all baseline and follow-up parameters. T-test was used for parametric distributions, the

Mann-Whitney-U test for non-parametric distributions.

All analyses were performed per protocol. A p-value of <0,05 was determined as significant

for all tests. Parametric data is stated with mean and standard deviation, non-parametric data

with median and range.

3.5.1 Software Tools The basic data collection was done with the spreadsheet program Microsoft Excel

(Microsoft, v16.0, 2015). For the statistical analysis, we used the software SPSS Statistics

(IBM, v25, 2015). For the compilation of the text document, we used the program Microsoft

Word (Microsoft, v16.0, 2015).

Quotations were made with the citation management software EndNote (Clarivate Analytics,

X8.2, 2018). For the literature search, we used the search engine PubMed (National Center

for Biotechnology Information). Additionally, we used the books available in the library of

the Medical University of Graz.

4 Results The first 18 patients and their preliminary results were included in the statistical analysis of

this diploma thesis. Ten in the group without IB and 8 in the group with IB. Figure 26 gives

an overview of the different follow-up periods in the two groups.

n=18Revision ACL

reconstruction

n=10without IB

n=1012 weeks follow-up

n=86 months follow-up

n=413 months follow-up

n=8with IB

n=812 weeks follow-up

n=66 months follow-up

n=413 months follow-up

Figure 26: Overview of Follow-Up Periods

38

The following results focus on preoperative data and the 12-month follow-up.

4.1 Patient demographics The final study population of 18 patients (16.7% female) had a mean age of 29.4 ± 7.8 years

at the day of surgery (Table 9).

4.2 Preoperative Data

4.2.1 Physical Examination During clinical examination the patients showed a mean total ROM of 133 ± 11 degrees.

None of them showed signs of inflammation, only 4 (22%) reported mild pain during

palpation. There were no abnormalities detected in motor activity, circulation or sensitivity.

All patients showed positive Lachman, Anterior Drawer and Lever sign tests and complained

about instability in the affected knee (Table 10).

Without IB With IB p-value

Patients (n) 10 8

Side, left/right (n) 4 / 6 5 / 3

Meniscal Lesion (n, (%))

7 (70) 7 (88)

Injury Mechanism (n, contact sport/

non-contact sport

/accident/unknown)

1 / 2 / 2 / 5 1 / 3 / 2 / 2

Sport-Level before

injury

(TAS, mean ± SD)

8.3 ± 1.0 7.1 ± 2.0 0.281

Smoking Habits

(packyears, mean ±

SD)

3.1 ± 3.5 6.5 ± 8.9 0.573

Table 9: Patient demographics, n=number, SD= standard deviation

39

4.2.2 Radiographic Evaluation Preoperative MRI scans and radiographs were performed in all patients. Preoperative

planning regarding graft size, bone block diameter, position of previously used graft, and

any structural damages were performed. A preoperative radiograph example can be seen in

Figure 27.

Without IB With IB p-value

Patients (n) 10 8

ROM

(degrees, mean ±

SD)

132.5 ± 10.3 134.3 ± 12.7 0.762

Pain during

palpation (n) 1 3

Table 10: Preoperative Physical Examination, n=number, ROM=Range of Motion, SD=standard deviation

Figure 27: Preoperative ap / lateral X-ray of a patient (LKH Universitätsklinikum Graz)

40

4.2.3 Clinical Scoring Systems The mean preoperative scores for the used questionnaires in both groups can be seen in Table

11.

Preoperatively, none of the evaluated scores showed any significant difference between the

two groups.

4.2.4 Short-Form 36 Health Survey The outcome variables of the eight subscales and the two summary scores were compared

between the two groups. There were no significant differences between the two groups in

five of the eight subscales, the PCS or the MCS (see Table 12). There were significant

differences between the two groups in the VT, RE, and MH subscale, showing better results

in the group without IB preoperatively, however without clinical relevance.

Without IB With IB p - Value

Patients (n) 10 8

VAS

(median/range)

1 /

0-7

1 /

0-5 0.696

Lysholm Knee Questionnaire

(mean ± SD) 3.3 ± 1.2 3.4 ± 2.1 0.923

TAS (mean ± SD)

3.4 ± 2.0 3.3 ± 1.0 0.848

KOOS (days, mean ± SD)

73.5 ± 9.1 64.6 ± 16.2 0.191

IKDC (days, mean ± SD)

60.0 ± 16.1 53.5 ± 17.3 0.419

Table 11: Preoperative Questionnaire Data, n=number, min=Minimum, max= Maximum, SD=standard deviation

Without IB With IB p - Value

Patients (n) 10 8

Physical Functioning (mean ± SD)

75.5 ± 13.8 67.5 ± 20.9 0.343

Role-Physical (mean ± SD)

63.8 ± 29.0 61.0 ± 33.9 0.851

41

Figure 28 shows the eight subscales, and Figure 29 presents the two summary scores of the

SF-36 comparing the two study groups.

Figure 28: Preoperative SF-36 Subscales

0102030405060708090

100

PF RP BP GH VT SF RE MH

Preoperative SF-36 Subscales

Without Internal Brace With Internal Brace

Bodily Pain (mean ± SD)

61.6 ± 24.8 52.5 ± 23.2 0.437

General Health (mean ± SD)

85.9 ± 9.2 81.0 ± 11.9 0.360

Vitality (mean ± SD) 72.5 ± 11.9 57.1 ± 18.7 0.049*

Social Functioning (mean ± SD)

88.8 ± 19.0 90.6 ± 17.4 0.897

Role-Emotional (mean ± SD)

95.0 ± 10.5 72.9 ± 20.3 0.027*

Mental Health (mean ± SD)

85.5 ± 8.0 71.9 ± 17.5 0.043*

Physical Component

Summary (mean ± SD) 44.7 ± 8.1 44.5 ± 8.6 0.964

Mental Component

Summary (mean ± SD) 62.2 ± 11.2 57.1 ± 11.8 0.362

Table 12: Preoperative SF-36 Results, ‘ = non-parametric data, * = statistically significant, SD=standard deviation

p=0.049*

p=0.027* p=0.043*

p=0.343 p=0.851 p=0.437

p=0.360 p=0.897

42

Figure 29: Preoperative SF-36 Summary Scores

4.3 Surgical Data Data regarding surgery and hospital stay can be seen in Table 13. In some cases, a Push Lock

Anchor (Arthrex ©) was used, to additionally secure the allograft on the tibial footprint area.

The results show no statistically significant difference regarding surgery data and hospital

stay between the two groups.

0

10

20

30

40

50

60

70

PCS MCS

Preoperative SF-36 Summary Scores

Without Internal Brace With Internal Brace

Without IB With IB p - Value

Patients (n) 10 8

Surgical Time (minutes, mean ± SD)

115.9 ± 27.5 117.6 ± 31.7 0.903

Allograft Diameter (mm, mean ± SD)

9.8 ± 0.6 9.5 ± 1.1 0.633

Pushlock (n (%)) 7 (70%) 5 (63%)

Hospital Stay (days, median / range)

5 / 4-7 5.5 / 4-6 0.315

Table 13: Surgical Data, SD=standard deviation, ‘ = non-parametric data

p=0.964

p=0.362

43

4.4 12-Week Follow-Up Data

4.4.1 Physical Examination During the clinical examination the patients showed a mean total ROM of 138 ± 7 degrees.

There was no statistical significance between the two groups (see Table 14).

None of them showed signs of inflammation, only 3 (17%) reported mild pain during

palpation. All patients had a good condition of scars. There were no abnormalities detected

in motor activity, circulation or sensitivity. All patients, except one in the group without IB,

showed negative Lachman, Anterior Drawer and Lever sign tests and had not experienced

any giving-way symptoms since surgery.

ROM is better 12 weeks after surgery compared to preoperative data, but the difference is

not statistically significant (see Table 15).

4.4.2 Clinical Scoring Systems The mean scores for the used questionnaires in both groups can be seen in Table 16.

Without IB With IB p – Value

Patients (n) 10 8

ROM

(degrees, mean ± SD) 139.5 ± 6.9 135.7 ± 7.9 0.315

Pain during palpation (n/%)

1/10 2/25

Table 14: 12-Week Physical Examination

ROM (degrees, mean ± SD)

Preoperatively After 12 Weeks p – Value

Without IB 132.5 ± 10.3 139.5 ± 6.9 0.221

With IB 134.3 ± 12.7 135.7 ± 7.9 0.785

Table 15: ROM=Range Of Motion

44

Twelve weeks after surgery the IKDC score in the group without IB was significantly better

than in the group with IB. The other applied scores showed no significant difference.

A graphic presentation of the data can be seen in Figure 30.

4.4.3 Short-Form 36 Health Survey There were no significant differences between the two groups in seven of the eight subscales,

the PCS or the MCS after 12 Weeks. There was one significant difference between the two

Without IB With IB p - Value

Patients (n) 10 8

VAS (median/

range)

1 /

0-3

1.5 /

0-5 0.145

Lysholm K.Q. (median /

min-max) 94 / 65-100 67 / 62-100 0.109

TAS (median / min-max)

4 / 3-4 3 / 3-4 0.315

KOOS (days, mean ± SD)

82.6 ± 9.8 74.8 ± 6.3 0.090

IKDC (days, mean ± SD)

74.7 ± 8.8 63.9 ± 8.7 0.024*

Table 16: 12-Week Questionnaire Data, *= statistically significant

0102030405060708090

KOOS IKDC

12-Week-Follow-Up-Data

Without IB With IB

p=0.024*p=0.090

Figure 31: 12-Week Follow-Up Data Figure 30: 12-Week Follow-Up Data

45

groups in the subscale Physical Functioning (PF), which showed better results for the group

without IB (see Table 17).

Without IB With IB p - Value

Patients (n) 10 8

Physical Functioning (mean ± SD)

88.0 ± 10.1 75.0 ± 14.1 0.042*

Role-Physical (mean ± SD)

72.5 ±30.8 66.1 ± 18.0 0.629

Bodily Pain (mean ± SD)

85.1 ± 18.7 64.9 ± 23.1 0.065

General Health (mean ± SD)

84.3 ± 12.5 72.1 ± 10.5 0.053

Vitality (mean ± SD)

78.2 ± 9.0 69.7 ± 11.7 0.133

Social Functioning (mean ± SD)

100.0 ± 0.0 85.7 ± 13.4 0.055

Role-Emotional (mean ± SD)

96.7 ± 10.5 86.9 ± 17.3 0.315

Mental Health (mean ± SD)

86.5 ± 5.3 81.4 ± 8.0 0.133

Physical Component

Summary (mean ± SD) 50.9 ± 6.4 45.0 ± 7.2 0.093

Mental Component

Summary (mean ± SD) 53.5 ± 7.4 57.4 ± 11.4 0.396

Table 17: 12-Week Follow-Up SF-36 Results, ‘ = non-parametric data, * = statistically significant

46

Figure 31 shows the eight subscales, and Figure 32 presents the two summary scores of the

SF-36 comparing the two study groups.

Figure 33 shows the comparison of the two study groups 12 weeks after surgery with the

score of the US normal population.

0

20

40

60

80

100

120

PF RP BP GH VT SF RE MH

12-Week Follow-Up SF-36 Subscales

Without IB With IB

p=0.042*

Figure 31: 12-Week Follow-Up SF-36 Subscales

0

10

20

30

40

50

60

PCS MCS

12-Week Follow-Up SF-36 Summary Scores

Without IB With IB

Figure 32: 12-Week Follow-Up SF-36 Summary Scores

p=0.629 p=0.065 p=0.053

p=0.133

p=0.055 p=0.315 p=0.133

p=0.093 p=0.396

Figure 32: 12-Week Follow-Up SF-36 Summary Scores

47

Figure 33: SF-36 Comparison With US Normal Population (red line shows US norm value)

Both groups had better results in five out of eight subscales (GH, VT, SF, RE, MH) 12 weeks

after surgery compared to the US norm population. In one subscale (RP) the US norm

population had a better result than both groups, and in two subscales (PF, BP) the group

without IB showed a better result than the US norm, whereas the group with IB showed

worse results than the US norm.

4.5 Case Presentation

4.5.1 Patient without internal bracing A 28-year old male patient presented himself with permanent pain and increasing instability

in the right knee existing for a few weeks. Several years ago, he had an ACL, TCL (tibial

collateral ligament), and medial meniscus rupture in the same knee and got an ACL

reconstruction with a hamstring autograft. Afterwards he was able to continue sports like

football and skiing, up until now. He played football in a hobby league and was working as

a technical employee. The first ACL rupture occurred during a football match, the second

time he could not determine the exact time or context of the re-rupture.

A MRI scan of the right knee, performed three months before consultation, showed an ACL

re-rupture, and in the physical examination the Lachman and Anterior Drawer tests were

positive.

0

10

20

30

40

50

60

70

PF RP BP GH VT SF RE MH

SF-36 Comparison With US Normal Population

Without IB With IB

48

With conservative therapy methods the patient was not able to decrease instability or pain or

to continue playing football.

After a stay of 5 days the patient was discharged. The rehabilitation proceeded uneventful

and as described in 3.3.7. After six weeks he was allowed to move the knee without using a

restrictive brace.

Figure 34: Preoperative X-Ray Case I

Figure 35: 6-Week follow-up X-Ray Case I (LKH Universitätsklinikum Graz)

49

Six months after surgery a MRI scan was performed, which showed a normally running ACL

graft (see Figure 36).

The MRI scan performed 13 months after surgery showed an intact ACL graft (see Figure

37).

Figure 36: 6-Month Follow-Up MRI Case I ((Diagnostikzentrum Graz für Computertomographie und Magnetresonanztomographie)

Figure 37: 13-Month Follow-Up MRI Case I (Diagnostikzentrum Graz für Computertomographie und Magnetresonanztomographie

50

The patient’s physical results increased over time and he felt very satisfied with the

postoperative progress. The questionnaire results were also constantly increasing (see Table

18).

The summary scores of the SF-36 over time can be seen in Table 19. After a postoperative

drop, the PCS was constantly increasing, after 13-months being higher than preoperatively.

The MCS shows a similar course, the score being lower after 13-months than preoperatively,

probably due to the fear of hurting the ACL again.

PCS MCS

Preoperative 52.5 50.8

After 6 Weeks 35.8 36.4

After 12 Weeks 56.3 47.3

After 6 Months 58.2 49.3

After 13 Months 59.5 45.3 Table 19: SF-36 Summary Scores Case I

Thirteen months after surgery the patient had no pain or instability in the affected knee and

was satisfied with the overall course. All clinical tests for ACL ruptures were negative and

VAS Lysholm K. Q. TAS KOOS IKDC

Preoperative 1 62 5 65.5 35.6

After 6 Weeks 1 62 2 62.8 54.0

After 12 Weeks 1 77 4 80.4 78.2

After 6 Months 1 100 5 95.8 86.2

After 13 Months 0 95 6 95.3 95.4

Table 18: Questionnaire Results Case I

51

his mobility unrestricted. He showed no signs of inflammation. Although he was allowed to

perform knee-strenuous sports, he was advised against stop-and-go movements and skiing

the following winter season.

4.5.2 Patient with internal bracing A 37-year old male patient presented himself with permanent instability in the left knee. A

few years back he ruptured his ACL and medial meniscus in the same knee and received

reconstruction surgery. The hamstring tendons of his left knee were used as an ACL graft.

A few days after surgery he developed a postoperative infection. He was treated with

intravenous antibiotics and his knee eventually healed without removing the implemented

graft. A few months ago he injured his left knee again while running. A performed MRI scan

showed a total re-rupture of the ACL graft. The patient demanded another surgery as he

wasn’t able to run long distances with an unstable knee.

After a stay of 4 days the patient could be discharged without any signs of inflammation.

The rehabilitation proceeded satisfactory, at the 6-week follow up his pain level was already

lower than before surgery.

Figure 38: Preoperative X-Ray Case II (LKH Universitätsklinikum Graz)

52

The MRI scan performed 6 months after surgery showed a slightly thickened, but normally

running ACL graft (see Figure 40).

Figure 39: 6-Week Follow-Up X-Ray Case II (LKH Universitätsklinikum Graz)

Figure 40: 6-Month Follow-Up Case II (Diagnostikzentrum Graz für Computertomographie und Magnetresonanztomographie)

53

After 13 months the performed MRI scan showed no changes (see Figure 41).

The results of the applied questionnaires and their course over time can be seen in Table 20.

The summary scores of the SF-36 show both a better result after 13 months compared to the

preoperative score (see Table 21).

PCS MCS

Preoperative 45.1 40.9

VAS Lysholm K. Q. TAS KOOS IKDC

Preoperative 4 48 4 62.5 48.3

After 6 Weeks 3 35 3 51.2 40.2

After 12 Weeks 3 66 4 69.6 65.5

After 6 Months 2 85 4 85.7 79.3

After 13 Months 0 94 5 85.5 82.8

Table 20: Questionnaire Results Case II

Figure 41: 13-Month Follow-Up MRI Case II (Diagnostikzentrum Graz für Computertomographie und Magnetresonanztomographie)

54

After 6 Weeks 32.7 52.4

After 12 Weeks 49.3 47.5

After 6 Months 51.9 44.1

After 13 Months 55.3 47.0 Table 21: SF-36 Summary Scores Case II

After 13 months the patient was free of pain. He had not experienced any instability since

surgery and was very satisfied with the result. All clinical ACL tests were negative and his

mobility unrestricted.

5 Discussion This study presents the first-time results of revision ACL reconstruction using an internal

brace in allografts. Previous published studies have only shown results regarding internal

bracing used in ACL repairs (85-88) or reconstructions with autografts (89).

The use of allografts in ACL reconstructions has been well-reviewed in the past.(4, 5, 56,

59) Despite the availability of a limited number of prospective, randomized, controlled

studies regarding this topic, there are a lot of meta-analyses.(58, 90-95) Most of them show

a small advantage of autografts compared to highly irradiated allografts (90, 91, 93, 94),

however, this difference disappears when comparing autografts with non-irradiated

allografts (90, 94). Grassi et al. (90) performed a meta-analysis of 32 studies regarding

revision ACL reconstruction with a minimum 2-year follow up. They showed that autografts

had better outcomes concerning laxity, complications, and re-operations when compared to

irradiated allografts, but that results no longer differed when compared to non-irradiated

grafts (90). Condello et al. (96) also found that allografts had no disadvantages compared to

autografts, provided that the tissue was not irradiated, or any radiation was minimal. High-

dose irradiation has been shown to impair mechanical strength of the graft. (96)

These findings support the use of non- or low-irradiated allografts in primary ACL

reconstructions and revision cases. However, they are mostly used in revision ACL

reconstruction. Bait et al. (97) recently published a consensus statement developed by Italian

orthopedic surgeons stating that allografts should be used as first-line graft in revision

55

situations, but not in primary reconstruction unless autografts are not available. This

recommendation is based on the overall inferior results of irradiated allografts and does not

consider non-irradiated allografts (97). Another reason for preferring reconstruction using

autografts are higher costs along with allografts. Mistry et al. (98) stated the costs of an ACL

reconstruction surgery using autografts with approximately 2250 pounds, including the

operation itself, pre- and aftercare. The costs for an allograft procedure reached 4400 pounds,

including the allograft with approximately 2250 pounds. (98)

Internal Brace (IB) fibre tape (Arthrex ©) is supposed to strengthen the whole graft construct

and protect it during the first healing phase.(9) It was tested in the repair of other ligaments

like the deltoid ligament (99), or the talofibular ligament (100), where it showed good results

and higher maximum load values than native ligaments and no significant difference in

ROM. (99, 100)

In primary ACL ruptures the Internal Brace was used to repair the native ACL. A report was

published by Arthrex © (85) showing that patients whose ACL had been repaired using an

IB, showed less pain and improved function two years postoperatively. However, due to the

lack of a control group it is not possible to say if the results of a possible reconstruction

surgery would have been better. (85) Jonkergouw et al. (87) conducted a study comparing

ACL repair with IB and without IB. They found no significant differences in outcomes

between the two groups and no failures related to the hardware. There were also no clinical

benefits, but they stated that the use of an IB could possibly be beneficial and larger cohorts

are needed to clearly answer this question. (87) In an animal study Seitz et al. (88)

demonstrated, that an augmented repair led to superior biomechanical results 16 weeks

postoperatively compared to a primary repair. (88) IB was also used in pediatric patients as

a temporary augmentation when performing an ACL repair. Smith et al. (86) used it in three

children with an ACL rupture, and removed the IB after 3 months. They reported complete

healing and stability in all three patients two years postoperatively. (86)

To our knowledge no study examining the effects of an IB augmentation in allografts used

in a revision ACL reconstruction was yet conducted. Our results show overall satisfactory

outcomes in both groups, with no relevant clinical difference. We used Achilles tendons in

both groups. The advantage of using the Achilles tendon is the availability of a bone block.

Compared to other allografts the failure rate is lower (101), it shows lower displacement,

and higher stiffness. (102) Further, the use of a bone block made a two-time approach with

56

previous bone building redundant, and the osseous fixation of the graft in the femoral tunnel

increased the overall stability of the graft. (103)

The use of an additional IB did not interfere with surgery time, being 115.9 minutes without

IB and 117.6 minutes with IB. The length of hospital stay did also not differ between the

two groups, being 5 days without IB and 5.5 days with IB. So, the use of an IB did not

lengthen surgery time or shorten hospital stay.

The lower IKDC and SF-36 subscale score for Physical Functioning in the group with IB

compared to the group without IB could be attributed to over-constriction of the graft. Smith

et al. (9) already described this phenomenon, which ultimately leads to loss of motion if the

IB is fixed too tight. (9) However, ROM in our study population was 139.5 degrees without

IB and 135.7 degrees with IB, and no patient showed relevant flexion or extension deficits

in the physical examination. No patient-reported signs of constriction of the affected knee.

The lower IKDC result in the IB group could, therefore, be just coincidental and disappear

with longer follow-up.

Our results show a mean Lysholm score of 94 without IB and 67 with IB. In current

literature, Lysholm scores ranged from 89 to 91 in autografts (92, 93) and 84.7 to 99 in

allografts (91). Respectively, these outcomes were reported after a minimum follow-up of

2-years in much larger cohorts. Although the results of the IB group seem lower, they were

not statistically significant and are likely to increase over time.

Similar results can be seen regarding the Tegner Activity Scale, ranging from 4.8 to 7.9 in

autografts and from 4.5 to 7.8 in allografts published in the meta-analysis of Wang et al.

(93). The mean TAS scores in our study were 4 in the group without IB and 3 in the group

with IB. The lower results can be easily explained, as the patients are not capable to return

to sport after just three months.

The IKDC ranges from 77.2 to 90 in autografts and 73.7 to 90 in allografts as described by

Wang et al. (93), compared to 74.7 without IB and 63.9 with IB in our study population. As

the IKDC mainly focuses on symptoms, function and sports activities (83), the low scores

after 12 weeks are not surprising. Respectively, all of our results evaluated after three months

are likely to increase over time. (see 4.5 Case Presentation).

The overall good SF-36 results in both groups could be explained by our study group being

generally healthier and younger than the compared US norm population. Considering that

the majority of ACL injuries occur to a young athletic population, and the SF-36 addresses

topics such as tiredness, sadness, and nervousness, which are more often found in a less

57

active population, these results should be viewed with caution and only be compared to

similar cohorts. (104)

5.1 Limitations and Strengths One drawback of our study is the short follow-up period of three months. The 13-month

follow-up of all included patients is supposed to deliver more detailed results. Another

drawback is the relatively small size of the study population, however this is due to the study

design of a pilot study. After sample size calculation based on our results further adequately

powered RCT will be planned. Still, based on the limited data regarding internal bracing in

current literature and lack of similar studies, our study cohort is still one of the largest.

Lifestyle factors have not been taken into consideration when forming the two study groups,

one of them being smoking habits. There was no statistically significant difference between

the two groups regarding packyears, but smoking itself interferes with healing processes,

making the study results impressionable. The activity level was also not considered during

the inclusion of the patients. Even though the difference in activity level was not statistically

significant, and there were no professional athletes included, the inter-patient differences

could affect the results.

The most prominent strength of this study is that it is the first prospective, randomized, and

blinded study regarding the use of internal braces in allografts in revision cases in current

literature. There are just a few other prospective, randomized, and blinded studies regarding

the use of allografts in revision cases, and none regarding the use of internal bracing in

allografts. Another strength is that we used the same allograft with the same processing in

all patients. Most other studies used differently processed allografts, thus making the data

hard to compare. Also, the relatively similar population in the two compared groups

regarding age and BMI strengthens the informative value of the study.

5.2 Conclusion This study provides the first HRQOL data and clinical results in patients treated with IB in

revision ACL reconstructions using allografts.

Revision ACL reconstruction using allografts with, as well as without IB, show good results

in short-term follow-up. There were no graft failures after 12 weeks in any of the groups.

The advantage of IB regarding outcome and failure rate could not yet be proven in this short

period of time. Prospective studies with larger cohorts and longer follow-up are needed.

58

6 References

1. Bollen S. Epidemiology of knee injuries: diagnosis and triage. Br J Sports Med. 2000;34. 2. AWMF Leitlinie: Vordere Kreuzbandruptur [Internet]. AWMF online. 2014 [cited 17.04.2017]. Available from: http://www.awmf.org/leitlinien/detail/ll/012-005.html. 3. Wright RW, Gill CS, Chen L, Brophy RH, Matava MJ, Smith MV, et al. Outcome of revision anterior cruciate ligament reconstruction: a systematic review. J Bone Joint Surg Am. 2012;94(6):531-6. 4. Mascarenhas R, Erickson BJ, Sayegh ET, Verma NN, Cole BJ, Bush-Joseph C, et al. Is there a higher failure rate of allografts compared with autografts in anterior cruciate ligament reconstruction: a systematic review of overlapping meta-analyses. Arthroscopy. 2015;31(2):364-72. 5. Nelson IR, Chen J, Love R, Davis BR, Maletis GB, Funahashi TT. A comparison of revision and rerupture rates of ACL reconstruction between autografts and allografts in the skeletally immature. Knee Surg Sports Traumatol Arthrosc. 2016;24(3):773-9. 6. Yao LW, Wang Q, Zhang L, Zhang C, Zhang B, Zhang YJ, et al. Patellar tendon autograft versus patellar tendon allograft in anterior cruciate ligament reconstruction: a systematic review and meta-analysis. Eur J Orthop Surg Traumatol. 2015;25(2):355-65. 7. Kane PW, Wascher J, Dodson CC, Hammoud S, Cohen SB, Ciccotti MG. Anterior cruciate ligament reconstruction with bone-patellar tendon-bone autograft versus allograft in skeletally mature patients aged 25 years or younger. Knee Surg Sports Traumatol Arthrosc. 2016;24(11):3627-33. 8. Steadman JR, Matheny LM, Hurst JM, Briggs KK. Patient-Centered Outcomes and Revision Rate in Patients Undergoing ACL Reconstruction Using Bone-Patellar Tendon-Bone Autograft Compared With Bone-Patellar Tendon-Bone Allograft: A Matched Case-Control Study. Arthroscopy. 2015;31(12):2320-6. 9. Smith PA, Bley JA. Allograft Anterior Cruciate Ligament Reconstruction Utilizing Internal Brace Augmentation. Arthrosc Tech. 2016;5(5):e1143-e7. 10. MacKay G, Anthony IC, Jenkins PJ, Blyth M. Anterior Cruciate Ligament Repair Revisited. Preliminary Results of Primary Repair with Internal Brace Ligament Augmentation: A Case Series. Orthop Muscul Syst. 2015;04(02). 11. Anderhuber F, Bechmann I, Filler TJ, Funk RHW, Linß W, Nitsch R, et al. Waldeyer - Anatomie des Menschen. Lehrbuch und Atlas in einem Band. Berlin, Boston: Walter de Gruyter GmbH & Co. KG; 2012. 1188 p. 12. Moore KL, Dalley AF, Agur AMR. Clinically Oriented Anatomy. Baltimore, Philadelphia: Lippincott Williams & Wilkins 2014. 13. Schünke M, Schulte E, Schumacher U. Prometheus LernAtlas der Anatomie. Allgemeine Anatomie und Bewegungssystem. Stuttgart: Georg Thieme Verlag; 2011. 14. Standring S, Anand N, Birch R, Collins P, Crossman AR, Gleeson M, et al. Gray's Anatomy. The Anatomical Basis of Clinical Practice.: Elsevier Limited; 2016. 15. Guenther D, Irarrázaval S, Nishizawa Y, Vernacchia C, Thorhauer E, Musahl V, et al. Variation in the shape of the tibial insertion site of the anterior cruciate ligament: classification is required. Knee Surg Sports Traumatol Arthrosc. 2017;25. 16. Tampere T, Van Hoof T, Cromheecke M, Van der Bracht H, Chahla J, Verdonk P, et al. The anterior cruciate ligament: a study on its bony and soft tissue anatomy using novel 3D CT technology. Knee Surg Sports Traumatol Arthrosc. 2017;25(1):236-44. 17. Amis AA, Dawkins GPC. Functional Anatomy of the Anterior Cruciate Ligament. Fibre Bundle Actions related to Ligament replacements and injuries. J Bone Joint Surg (br). 1991.

59

18. Fujimaki Y, Thorhauer E, Sasaki Y, Smolinski P, Tashman S, Fu FH. Quantitative In Situ Analysis of the Anterior Cruciate Ligament: Length, Midsubstance Cross-sectional Area, and Insertion Site Areas. Am J Sports Med. 2016;44(1):118-25. 19. S´migielski R, Drwie˛ga M, Zdanowicz U, Ciszek B, Ciszkowska-Łyson´ B, Siebold R. Ribbon like appearance of the midsubstance fibres of the anterior cruciate ligament close to its femoral insertion site: a cadaveric study including 111 knees. Knee Surg Sports Traumatol Arthrosc. 2015;23. 20. Strocchi R, De Pasquale V, Gubellini P, Facchini A, Marcacci M, Buda R, et al. The human anterior cruciate ligament: histological and ultrastructural observations. J Anat. 1992. 21. Aumüller G, Aust G, Doll A, Engele J, Kirsch J, Mense S, et al. Duale Reihe. Anatomie. Stuttgart: Thieme Verlag KG; 2010. 22. Hebert-Blouin M-N, Tubbs RS, Spinner RJ. Hilton’s Law Revisited. Clinical Anatomy. 2014;27. 23. Deehan DJ, Cawston TE. The biology of integration of the anterior cruciate ligament. J Bone Joint Surg (br). 2005;87(7). 24. Kiapour AM, Demetropoulos CK, Kiapour A, Quatman CE, Wordeman SC, Goel VK, et al. Strain Response of the Anterior Cruciate Ligament to Uniplanar and Multiplanar Loads During Simulated Landings: Implications for Injury Mechanism. Am J Sports Med. 2016;44(8):2087-96. 25. Kim SY, Spritzer CE, Utturkar GM, Toth AP, Garrett WE, DeFrate LE. Knee Kinematics During Noncontact Anterior Cruciate Ligament Injury as Determined From Bone Bruise Location. Am J Sports Med. 2015;43(10):2515-21. 26. Kittl C, El-Daou H, Athwal KK, Gupte CM, Weiler A, Williams A, et al. The Role of the Anterolateral Structures and the ACL in Controlling Laxity of the Intact and ACL-Deficient Knee. Am J Sports Med. 2016;44(2):345-54. 27. Friden T, Roberts D, Movin T, Wredmark T. Function after anterior cruciate ligament injuries: Influence of visual control and proprioception. Acta Orthopaedica Scandinavica. 1998;69(6):590-4. 28. Hofbauer M, Thorhauer ED, Abebe E, Bey M, Tashman S. Altered tibiofemoral kinematics in the affected knee and compensatory changes in the contralateral knee after anterior cruciate ligament reconstruction. Am J Sports Med. 2014;42(11):2715-21. 29. Woo SL-Y, Vogrin TM, Abramowitch SD. Healing and repair of ligament injuries in the knee. J Am Acad Orthop Surg. 2000. 30. Howell SM, Knox KE, Farley TE, Taylor MA. Revascularization of a Human Anterior Cruciate Ligament graft during the first two years of Implantation. Am J Sports Med. 1995;23(1). 31. Hewett TE, Myer GD, Ford KR, Heidt RS, Jr., Colosimo AJ, McLean SG, et al. Biomechanical measures of neuromuscular control and valgus loading of the knee predict anterior cruciate ligament injury risk in female athletes: a prospective study. Am J Sports Med. 2005;33(4):492-501. 32. Sutton KM, Bullock JM. Anterior Cruciate Ligament Rupture: Differences Between Males and Females. J Am Acad Orthop Surg. 2013. 33. Levins JG, Sturnick DR, Argentieri EC, Gardner-Morse M, Vacek PM, Desarno MJ, et al. Geometric Risk Factors Associated With Noncontact Anterior Cruciate Ligament Graft Rupture. Am J Sports Med. 2016;44(10):2537-45. 34. Walden M, Atroshi I, Magnusson H, Wagner P, Hagglund M. Prevention of acute knee injuries in adolescent female football players: cluster randomised controlled trial. BMJ. 2012;344:e3042. 35. Rahr-Wagner L, Thillemann TM, Mehnert F, Pedersen AB, Lind M. Is the use of oral contraceptives associated with operatively treated anterior cruciate ligament injury? A

60

case-control study from the Danish Knee Ligament Reconstruction Registry. Am J Sports Med. 2014;42(12):2897-905. 36. Beynnon BD, Vacek PM, Newell MK, Tourville TW, Smith HC, Shultz SJ, et al. The Effects of Level of Competition, Sport, and Sex on the Incidence of First-Time Noncontact Anterior Cruciate Ligament Injury. Am J Sports Med. 2014;42(8):1806-12. 37. Johnsen MB, Guddal MH, Smastuen MC, Moksnes H, Engebretsen L, Storheim K, et al. Sport Participation and the Risk of Anterior Cruciate Ligament Reconstruction in Adolescents: A Population-based Prospective Cohort Study (The Young-HUNT Study). Am J Sports Med. 2016;44(11):2917-24. 38. Lichtenberg MC, H. C, Teunissen LPJ, Oosterveld FGJ, Harmsen AMK, Haverkamp D, et al. Does the Lever Sign Test Have Added Value for Diagnosing Anterior Cruciate Ligament Ruptures? The Orthopaedic Journal of Sports Medicine. 2018;6. 39. Benjaminse A, Gokeler A, van der Schans CP. Clinical diagnosis of an anterior cruciate ligament rupture: a meta-analysis. J Orthop Sports Phys Ther. 2006;36(5):267-88. 40. Malanga GA, Andrus S, Nadler SF, McLean J. Physical examination of the knee: a review of the original test description and scientific validity of common orthopedic tests. Arch Phys Med Rehabil. 2003;84(4):592-603. 41. Lelli A, Di Turi RP, Spenciner DB, Domini M. The "Lever Sign": a new clinical test for the diagnosis of anterior cruciate ligament rupture. Knee Surg Sports Traumatol Arthrosc. 2016;24(9):2794-7. 42. Shea KG, Carey JI. Management of Anterior Cruciate Ligament Injuries: Evidence-Based Guideline. J Am Acad Orthop Surg. 2015;23(5). 43. Biercevicz AM, Akelman MR, Fadale PD, Hulstyn MJ, Shalvoy RM, Badger GJ, et al. MRI volume and signal intensity of ACL graft predict clinical, functional, and patient-oriented outcome measures after ACL reconstruction. Am J Sports Med. 2015;43(3):693-9. 44. Neuman P, Englund M, Kostogiannis I, Friden T, Roos H, Dahlberg LE. Prevalence of Tibiofemoral Osteoarthritis 15 Years After Nonoperative Treatment of Anterior Cruciate Ligament Injury. A Prospective Cohort Study. Am J Sports Med. 2008;36(9). 45. Frobell RB, Roos EM, Roos HP, Ranstam J, Lohmander LS. A Randomized Trial of Treatment for Acute Anterior Cruciate Ligament Tears. N Engl J Med. 2010. 46. Frobell RB, Roos HP, Roos EM, Roemer FW, Ranstam J, Lohmander LS. Treatment for acute anterior cruciate ligament tear: five year outcome of randomised trial. BMJ. 2013;346:f232. 47. Ramski DE, Kanj WW, Franklin CC, Baldwin KD, Ganley TJ. Anterior cruciate ligament tears in children and adolescents: a meta-analysis of nonoperative versus operative treatment. Am J Sports Med. 2014;42(11):2769-76. 48. Spindler KP, Wright RW. Anterior Cruciate Ligament Tear. N Engl J Med. 2008. 49. Raviraj A, Anand A, Kodikal G, Chandrashekar M, Pai S. A comparison of early and delayed asthroscopically-assisted reconstruction of the anterior cruciate ligament using hamstring autograft. J Bone Joint Surg (br). 2010. 50. Wierer G, Runer A, Hoser C, Herbst E, Gfoller P, Fink C. Acute ACL reconstruction in patients over 40 years of age. Knee Surg Sports Traumatol Arthrosc. 2016. 51. Vavken P, Murray MM. The potential for primary repair of the ACL. Sports Med Arthrosc. 2011;19(1):44-9. 52. Di Matteo B, Loibl M, Andriolo L, Filardo G, Zellner J, Koch M, et al. Biologic agents for anterior cruciate ligament healing: A systematic review. World J Orthop. 2016;7(9):592-603. 53. Hao ZC, Wang SZ, Zhang XJ, Lu J. Stem cell therapy: a promising biological strategy for tendon-bone healing after anterior cruciate ligament reconstruction. Cell Prolif. 2016;49(2):154-62.

61

54. West RV, Harner CD. Graft Selection in Anterior Cruciate Ligament Reconstruction. J Am Acad Orthop Surg. 2005;13. 55. Murawski CD, van Eck CF, Irrgang JJ, Tashman S, Fu FH. Operative treatment of primary anterior cruciate ligament rupture in adults. J Bone Joint Surg Am. 2014;96(8):685-94. 56. Prodromos CC, Fu FH, Howell SM, Johnson DH, Lawhorn K. Controversies in Soft-tissue Anterior Cruciate Ligament Reconstruction: grafts, bundles, tunnels, fixation and, harvest. J Am Acad Orthop Surg. 2008. 57. Maletis GB, Chen J, Inacio MCS, Love RM, Funahashi TT. Increased Risk of Revision After Anterior Cruciate Ligament Reconstruction With Soft Tissue Allografts Compared With Autografts: Graft Processing and Time Make a Difference. Am J Sports Med. 2017;45(8):1837-44. 58. Kan SL, Yuan ZF, Ning GZ, Yang B, Li HL, Sun JC, et al. Autograft versus allograft in anterior cruciate ligament reconstruction: A meta-analysis with trial sequential analysis. Medicine (Baltimore). 2016;95(38):e4936. 59. Joyce CD, Randall KL, Mariscalco MW, Magnussen RA, Flanigan DC. Bone-Patellar Tendon-Bone Versus Soft-Tissue Allograft for Anterior Cruciate Ligament Reconstruction: A Systematic Review. Arthroscopy. 2016;32(2):394-402. 60. Dustmann M, Schmidt T, Gangey I, Unterhauser FN, Weiler A, Scheffler SU. The extracellular remodeling of free-soft-tissue autografts and allografts for reconstruction of the anterior cruciate ligament: a comparison study in a sheep model. Knee Surg Sports Traumatol Arthrosc. 2008;16(4):360-9. 61. Satora W, Krolikowska A, Czamara A, Reichert P. Synthetic grafts in the treatment of ruptured anterior cruciate ligament of the knee joint. Polim Med. 2017;47(1):55-9. 62. Machotka Z, Scarborough I, Duncan W, Kumar S, Perraton L. Anterior cruciate ligament repair with LARS (ligament advanced reinforcement system): a systematic review. Sports Med Arthrosc Rehabil Ther Technol. 2010;2:29. 63. Tiefenboeck TM, Thurmaier E, Tiefenboeck MM, Ostermann RC, Joestl J, Winnisch M, et al. Clinical and functional outcome after anterior cruciate ligament reconstruction using the LARS system at a minimum follow-up of 10 years. Knee. 2015;22(6):565-8. 64. Mayr HO, Zeiler C. [Complications after cruciate ligament reconstruction]. Orthopade. 2008;37(11):1080-7. 65. Lohmander LS, Englund PM, Dahl LL, Roos EM. The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med. 2007;35(10):1756-69. 66. Ajuied A, Wong F, Smith C, Norris M, Earnshaw P, Back D, et al. Anterior cruciate ligament injury and radiologic progression of knee osteoarthritis: a systematic review and meta-analysis. Am J Sports Med. 2014;42(9):2242-52. 67. Barenius B, Ponzer S, Shalabi A, Bujak R, Norlen L, Eriksson K. Increased risk of osteoarthritis after anterior cruciate ligament reconstruction: a 14-year follow-up study of a randomized controlled trial. Am J Sports Med. 2014;42(5):1049-57. 68. Pullen WM, Bryant B, Gaskill T, Sicignano N, Evans AM, DeMaio M. Predictors of Revision Surgery After Anterior Cruciate Ligament Reconstruction. Am J Sports Med. 2016;44(12):3140-5. 69. Lynch ST, Parker RD, Patel RM, Andrish JT, Spindler KP. The Impact of the Multicenter Orthopaedic Outcomes Network (MOON) Research on Anterior Cruciate Ligament Reconstruction and Orthopaedic Practice. J Am Acad Orthop Surg. 2015;23:154-63.

62

70. Yabroudi MA, Bjornsson H, Lynch AD, Muller B, Samuelsson K, Tarabichi M, et al. Predictors of Revision Surgery After Primary Anterior Cruciate Ligament Reconstruction. Orthop J Sports Med. 2016;4(9):2325967116666039. 71. Andernord D, Desai N, Bjornsson H, Ylander M, Karlsson J, Samuelsson K. Patient predictors of early revision surgery after anterior cruciate ligament reconstruction: a cohort study of 16,930 patients with 2-year follow-up. Am J Sports Med. 2015;43(1):121-7. 72. Di Benedetto P, Di Benedetto E, Fiocchi A, Beltrame A, Causero A. Causes of Failure of Anterior Cruciate Ligament Reconstruction and Revision Surgical Strategies. Knee Surg Relat Res. 2016;28(4):319-24. 73. Cheatham SA, Johnson DL. Anticipating problems unique to revision ACL surgery. Sports Med Arthrosc. 2013;21(2):129-34. 74. Maak TG, Voos JE, Wickiewicz TI, Warren RF. Tunnel widening in revision Anterior Cruciate Ligament reconstruction. J Am Acad Orthop Surg. 2010;18. 75. Anand BS, Feller JA, Richmond AK, Webster KE. Return-to-Sport Outcomes After Revision Anterior Cruciate Ligament Reconstruction Surgery. Am J Sports Med. 2016;44(3):580-4. 76. Grodski M, Marks R. Exercises following anterior cruciate ligament reconstructive surgery: biomechanical considerations and efficacy of current approaches. Res Sports Med. 2008;16(2):75-96. 77. Ardern CL, Taylor NF, Feller JA, Whitehead TS, Webster KE. Sports participation 2 years after anterior cruciate ligament reconstruction in athletes who had not returned to sport at 1 year: a prospective follow-up of physical function and psychological factors in 122 athletes. Am J Sports Med. 2015;43(4):848-56. 78. Dunn WR, Wolf BR, Harrell FE, Jr., Reinke EK, Huston LJ, Group MK, et al. Baseline predictors of health-related quality of life after anterior cruciate ligament reconstruction: a longitudinal analysis of a multicenter cohort at two and six years. J Bone Joint Surg Am. 2015;97(7):551-7. 79. Palmeri M, Morgan CD. The all-inside anterior cruciate ligament reconstruction: A double socket approach. Oper Tech Orthop. 1996;6:161-76. 80. Lubowitz JH. All-inside ACL: Retroconstruction Controversies. Sports Med Arthrosc Rev. 2010;18(1):20-6. 81. Lubowitz JH, Amhad CH, Anderson K. All-Inside Anterior Cruciate Ligament Graft-Link Technique: Second-Generation, No-Incision Anterior Cruciate Ligament Reconstruction. Arthroscopy. 2011;27(5):717-27. 82. LifeNet Health [01.03.2019]. Available from: https://www.lifenethealth.org. 83. Collins NJ, Misra D, Felson DT, Crossley KM, Roos EM. Measures of Knee Function. Arthritis Care Res. 2011;63:208-28. 84. Lins L, Carvalho FM. SF-36 total score as a single measure of health-related quality of life: Scoping review. SAGE Open Medicine. 2016;4. 85. Arthrex. ACL Repair with InternalBrace™ Ligament Augmentation 2019 [Available from: https://www.arthrex.com/foot-ankle/internalbrace-ligament-augmentation-repair. 86. Smith JO, Yasen SK, Palmer HC, Lord BR, Britton EM, Wilson AJ. Paediatric ACL repair reinforced with temporary internal bracing. Knee Surg Sports Traumatol Arthrosc. 2016;24(6):1845-51. 87. Jonkergouw A, van der List JP, DiFelice GS. Arthroscopic primary repair of proximal anterior cruciate ligament tears: outcomes of the first 56 consecutive patients and the role of additional internal bracing. Knee Surgery, Sports Traumatology, Arthroscopy 2019;27:21–8.

63

88. Seitz H, Pichl W, Matzi V, Nau T. Biomechanical evaluation of augmented and nonaugmented primary repair of the anterior cruciate ligament: an in vivo animal study. International Orthopaedics. 2013;37:2305-11. 89. Aboalata M, Elazab A, Halawa A, Ahmed MS, Imhoff AB, Bassiouny Y. The Crossing Internal Suture Augmentation Technique to Protect the All-Inside Anterior Cruciate Ligament Reconstruction Graft. Arthroscopy Techniques. 2017;6(6):e2235-e40. 90. Grassi A, Nitri M, Moulton SG, Marcheggiani Muccioli GM, Bondi A, Romagnoli M, et al. Does the type of graft affect the outcome of revision anterior cruciate ligament reconstruction?. A meta-analysis of 32 studies. Bone Joint J. 2017;99-B:714-23. 91. Kraeutler MJ, Bravman JT, McCarty EC. Bone–Patellar Tendon–Bone Autograft Versus Allograft in Outcomes of Anterior Cruciate Ligament Reconstruction. A Meta-analysis of 5182 Patients. Am J Sports Med. 2013;41(10):2439-48. 92. Wei J, Yang H-b, Qin J-b, Yang T-b. A meta-analysis of anterior cruciate ligament reconstruction with autograft compared with nonirradiated allograft. The Knee. 2015;22:37-379. 93. Wang S, Zhang C, Cai Y, Lin X. Autograft or Allograft? Irradiated or Not? A Contrast Between Autograft and Allograft in Anterior Cruciate Ligament Reconstruction: A Meta-analysis. Arthroscopy. 2018;34(12):3258-65. 94. Zeng C, Gao SG, Li H, Yang T, Luo W, Li YS, et al. Autograft Versus Allograft in Anterior Cruciate Ligament Reconstruction: A Meta-analysis of Randomized Controlled Trials and Systematic Review of Overlapping Systematic Reviews. Arthroscopy. 2016;32(1):153-63 e18. 95. Prodromos C, Joyce B, Shi K. A meta-analysis of stability of autografts compared to allografts after anterior cruciate ligament reconstruction. Knee Surg Sports Traumatol Arthrosc. 2007;15(7):851-6. 96. Condello V, Zdanowicz U, Di Matteo B, Spalding T, Gelber PE, Adravanti P, et al. Allograft tendons are a safe and effective option for revision ACL reconstruction: a clinical review. Knee Surgery, Sports Traumatology, Arthroscopy 2019;27:1771–81. 97. Bait C, Randelli P, Compagnoni R, Ferrua P, Papalia R, Familiari F, et al. Italian consensus statement for the use of allografts in ACL reconstructive surgery. Knee Surgery, Sports Traumatology, Arthroscopy 2019;27:1873-81. 98. Mistry H, Metcalfe A, Colquitt J, Loveman E, Smith NA, Royle P, et al. Autograft or allograft for reconstruction of anterior cruciate ligament: a health economics perspective. Knee Surgery, Sports Traumatology, Arthroscopy. 2019;27:1782–90. 99. Rigby RB, Fleming J, Development ARa. InternalBrace™ Ligament Augmentation in the Repair of Acute Deltoid Rupture Associated With Ankle Fracture. In: inc. A, editor. 2019. 100. Liebler S, Waldrop N. InternalBrace™ Ligament Augmentation: Biomechanical Testing of an Anterior Talofibular Ligament Repair as a Function of SwiveLock® Anchor Size, Drill Bit Diameter and Bone Tap Size. In: inc. A, editor. 2015. 101. Siebold R, Buelow JU, Bos L, Ellermann A. Primary ACL reconstruction with fresh-frozen patellar versus Achilles tendon allografts. Arch Orthop Trauma Surg. 2003;123(4):180-5. 102. Mabe I, Hunter S. Quadriceps tendon allografts as an alternative to Achilles tendon allografts: a biomechanical comparison. Cell Tissue Bank. 2014;15(4):523-9. 103. Grafe MW, Kurzweil PR. Anterior Cruciate Ligament Reconstruction With Achilles Tendon Allografts in Revisions and in Patients Older Than 30. Am J Orthop. 2008. 104. Filbay SR, Ackerman IN, Russell TG, Macri EM, Crossley KM. Health-related quality of life after anterior cruciate ligament reconstruction: a systematic review. Am J Sports Med. 2014;42(5):1247-55.

64

7 Appendix – Informed Consent, Case Report Form, Questionnaires

65

66

67

68

69

70

71

72

73

74

75

76

77

78

79

80

81

82

83

84

85

86

87

88

89