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Paper 37
Characterization of Growth Factors, Cytokines and Chemokines in Bone Marrow Concentrate and Platelet Rich Plasma: A Prospective Analysis
Connor G. Ziegler, MD1, Rachel Van Sloun2, Sabrina Gonzalez3, Kaitlyn E. Whitney2, Nicholas N. DePhillipo2, Mitchell Kennedy, BS2, Grant Dornan, MSc2, Thos A. Evans, MD2, Johnny Huard, PhD2, Robert F. LaPrade, MD, PhD4.1New England Orthopedic Surgeons, Springfield, MA, USA, 2Steadman Philippon Research Institute, Vail,CO, USA, 3Steadman Philippon Research Institute Program, Vail, CO, USA, 4The Steadman Clinic, Vail, CO,USA.
Objectives: Autologous platelet-rich plasma (PRP) and bone marrow concentrate (BMC) are orthobiologic therapies with numerous growth factors and cytokines. Mesenchymal stem cells (MSCs) are also present in BMC; however, comprise a very limited component of the available monocytes. Other clinically relevant factors and cytokines, including interleukin-1 receptor antagonist (IL-1Ra), are implicated in the anti-inflammatory and regenerative processes. Prior to optimizing the clinical utility of PRP and BMC as a combined or monotherapy, an improved understanding of the components and respective concentrations is necessary. The purpose of this study was to prospectively measure and compare anabolic, catabolic, anti-inflammatory and pro-inflammatory factors, proteins and cytokines present in bone marrow aspirate (BMA), BMC, whole blood, leukocyte poor (LP)-PRP and leukocyte rich (LR)-PRP from samples collected and processed concurrently from patients presenting for elective knee surgery.
Methods: A total of 31 patients presenting for elective knee surgery were prospectively enrolled over a three-week period. Whole blood from peripheral venous draw and BMA from the posterior iliac crest were immediately processed using centrifugation and manual extraction methods to create LR- and LP-PRP and BMC, respectively. BMA, BMC, whole blood, LR-PRP and LP-PRP samples were immediately assayed and analyzed to measure factor and cytokine concentrations. We strictly adhered to the minimum reporting requirements for biological outcomes (MIBO). An a priori power and sample size calculation was performed. We conservatively assumed a Bonferroni correction among all 10 pairwise comparisons, two-tailed testing, and an overall alpha level of 0.05. Eighteen subjects was sufficient to detect this magnitude of effect size with 80% statistical power.
Results: BMC had a significantly higher IL-1Ra concentration than all other preparations (all p < 0.0009, Figure 1). LR-PRP had a significantly higher IL-1Ra concentration than LP-PRP (p = 0.0006). There were no significant differences in IL-1Ra concentration based on age, gender, body mass index or chronicity of injury among all preparations (Table 1). BMC had significantly higher concentrations of leukocytes and monocytes compared to the other biologic preparations including LR-PRP. LP-PRP had significantly higher concentrations of matrix metalloproteinase (MMP)-2, MMP-3 and MMP-12 than all other preparations (all p < 0.007), while BMC had a significantly lower concentration of MMP-2 than all other preparations. LR-PRP had significantly higher concentrations of MMP-1, serum soluble CD40 ligand (sCD40L), platelet derived growth factor (PDGF)-AA and PDGF-AB/BB than all other preparations (all p < 0.004).
Conclusion: BMC is a clinically relevant source of anti-inflammatory biologic therapy that may be more effective in treating osteoarthritis and for use as an intra-articular biologic for augmented healing in the post-surgical inflammatory and healing phases due to its significantly higher concentration of IL-1Ra compared to LR-PRP and LP-PRP. Additionally, LR-PRP had a significantly higher concentration of IL-1Ra than LP-PRP. In cases where increased vascularity and healing are desired for pathological or injured tissues including muscle and tendon, LR-PRP may be optimal due to its higher overall concentrations of PDGF, TGF-β, EGF, VEGF, and sCD40L.
Paper 38 Meniscus Repair Outcomes with and without Bone Marrow Aspiration Concentrate Patrick Allan Massey, MD1, Andrew Zhang, MD1, Christine Bayt Stairs, MD1, Stephen Hoge, MD1, Trevor Carroll1, Ashley Marie Hamby2. 1Louisiana State University Health Sciences Center, Shreveport, LA, 2The Orthopedic Clinic, Shreveport, LA Objectives: The purpose of the current study is to review the results of meniscus repairs with and without bone marrow aspiration concentrate (BMAC). It is hypothesized that with BMAC, meniscus repair outcomes will be improved when compared to without BMAC at 1 year after surgery. Methods: This is a prospective case control study performed from August 2014 until August 2017. Patients were included if they had a meniscus repair performed with no history of prior meniscus surgery to the operative knee. Patients were excluded if there was a full thickness cartilage tear or International Cartilage Repair Society (ICRS) Grade IV cartilage tear not treated in a single staged surgery. Patients were also excluded if they did not reach the one year follow-up, had a multi-ligamentous knee injury requiring multiple staged procedures. From August 2014 until November 2015, patients had meniscus repair without BMA. Menisci were all repaired arthroscopically using inside-out, outside-in and all-inside techniques. After November 2015, all meniscus repairs were augmented with BMAC. In the BMAC group, all bone marrow was obtained from the ipsilateral femur during the time of surgery. The Biocue BMAC system (Zimmer Biomet, Warsaw Indiana) was used for bone marrow aspiration and BMAC was injected directly into the tear site after repair. Numerical data such as VAS, lysholm and IKDC was analyzed using a 2 sample T-test. Categorical data such as sex, tear location, type of tear and zone of tear were analyzed using a chi-square. Results: A total of 150 patients were initially included in the study. The average age in the control group was 26.3 versus 29.4 in the BMAC group (P=0.27). Thirty seven percent of the control group had an ACL reconstruction versus 40 % in the BMAC group (P= .77). The control group improved from an average pain level of 6.1 to 1.2 and the BMAC group improved from an average pain level of 5.9 to 0.7 at the 1 year end point. Both the control group and BMAC group improved with respect to pain with no difference at the 1 year end point (P=.19). There was, however a significantly larger reduction in pain at the 6 week and 3 month time point with BMAC compared to the control group (P=.02 and P=.02 respectively).
At the 1-year follow-up, the mean lysholm score improved from 43 to 92 in the control group and 43 to 90 in the BMAC group. The mean IKDC score improved from 37 to 87 in the control group and 36 to 83 in the BMAC group at the one year follow-up. Conclusion: Meniscus repair outcomes were improved at 6 weeks and 3 months post-operatively, when BMAC is used to augment meniscus repair compared to repair without BMAC. Both groups, control group and BMAC meniscus repair group had improved outcomes at 1 year post-operatively with respect to VAS, lysholm and IKDC, with no difference in complication rate.
Paper 39 Characterization of Growth Factors, Cytokines and Chemokines in Bone Marrow Concentrate and Platelet Rich Plasma: A Prospective Analysis Connor G. Ziegler, MD1, Rachel Van Sloun2, Sabrina Gonzalez3, Kaitlyn E. Whitney2, Nicholas N. DePhillipo2, Mitchell Kennedy, BS2, Grant Dornan, MSc2, Thos A. Evans, MD2, Johnny Huard, PhD2, Robert F. LaPrade, MD, PhD4. 1New England Orthopedic Surgeons, Springfield, MA, 2Steadman Philippon Research Institute, Vail, CO, 3Steadman Philippon Research Institute Program, Vail, CO, 4The Steadman Clinic, Vail, CO Objectives: Autologous platelet-rich plasma (PRP) and bone marrow concentrate (BMC) are orthobiologic therapies with numerous growth factors and cytokines. Mesenchymal stem cells (MSCs) are also present in BMC; however, comprise a very limited component of the available monocytes. Other clinically relevant factors and cytokines, including interleukin-1 receptor antagonist (IL-1Ra), are implicated in the anti-inflammatory and regenerative processes. Prior to optimizing the clinical utility of PRP and BMC as a combined or monotherapy, an improved understanding of the components and respective concentrations is necessary. The purpose of this study was to prospectively measure and compare anabolic, catabolic, anti-inflammatory and pro-inflammatory factors, proteins and cytokines present in bone marrow aspirate (BMA), BMC, whole blood, leukocyte poor (LP)-PRP and leukocyte rich (LR)-PRP from samples collected and processed concurrently from patients presenting for elective knee surgery. Methods: A total of 31 patients presenting for elective knee surgery were prospectively enrolled over a three-week period. Whole blood from peripheral venous draw and BMA from the posterior iliac crest were immediately processed using centrifugation and manual extraction methods to create LR- and LP-PRP and BMC, respectively. BMA, BMC, whole blood, LR-PRP and LP-PRP samples were immediately assayed and analyzed to measure factor and cytokine concentrations. We strictly adhered to the minimum reporting requirements for biological outcomes (MIBO). An a priori power and sample size calculation was performed. We conservatively assumed a Bonferroni correction among all 10 pairwise comparisons, two-tailed testing, and an overall alpha level of 0.05. Eighteen subjects was sufficient to detect this magnitude of effect size with 80% statistical power. Results: BMC had a significantly higher IL-1Ra concentration than all other preparations (all p < 0.0009, Figure 1). LR-PRP had a significantly higher IL-1Ra concentration than LP-PRP (p = 0.0006). There were no significant differences in IL-1Ra concentration based on age, gender, body mass index or chronicity of injury among all preparations (Table 1). BMC had significantly higher concentrations of leukocytes and monocytes compared to the other biologic preparations including LR-PRP. LP-PRP had significantly higher concentrations of matrix metalloproteinase (MMP)-2, MMP-3 and MMP-12 than all other preparations (all p < 0.007), while BMC had a significantly lower concentration of MMP-2 than all other preparations. LR-PRP had significantly higher concentrations of MMP-1, serum soluble CD40 ligand (sCD40L), platelet derived growth factor (PDGF)-AA and PDGF-AB/BB than all other preparations (all p <
0.004). Conclusion: BMC is a clinically relevant source of anti-inflammatory biologic therapy that may be more effective in treating osteoarthritis and for use as an intra-articular biologic for augmented healing in the post-surgical inflammatory and healing phases due to its significantly higher concentration of IL-1Ra compared to LR-PRP and LP-PRP. Additionally, LR-PRP had a significantly higher concentration of IL-1Ra than LP-PRP. In cases where increased vascularity and healing are desired for pathological or injured tissues including muscle and tendon, LR-PRP may be optimal due to its higher overall concentrations of PDGF, TGF-β, EGF, VEGF, and sCD40L.
Paper 40 The Cost Variability of Orthobiologics Brent Ponce, MD1, Andrew McGee1, Alex Dombrowsky1, Raymond Waldrop1, Joshua Wild1, Naqeeb Faroqui1, Samuel Roswell Huntley2, Kennieth Charles McCollough3, Eugene W. Brabston, MD4, Amit Mukesh Momaya, MD1. 1University of Alabama at Birmingham, Birmingham, AL, 2University of Alabama at Birmingha, Birmingham, AL, 3UAB Department of Orthopaedic Surgery, Birmingham, AL, 4University of Alabama at Birmingam, Birmingham, AL Objectives: Despite limited clinical data, many orthopedic practices offer orthobiologic injections. Such injections are not covered by insurance, and thus patients pay out of pocket for these treatments. The purpose of this study was to assess the variability in costs for platelet rich plasma (PRP) and stem cell (SC) injections across practices and evaluate for variables that influence pricing. Methods: A list of 1,345 orthopedic sports medicine practices across the United States was compiled. Calls were made inquiring into the availability of PRP or SC knee injections and associated costs. In addition to pricing, practice type (academic or private), number of providers, and population and income demographics were recorded. Univariate statistical analyses were used to identify differences in availability and cost between variables. Results: Of the contacted offices, 268 (20.2%) offered both treatments, 550 (41.5%) offered only PRP injections, 20 (1.5%) offered only stem cell injections, and 487 (36.2%) did not offer either treatment. The mean (± SD) cost of a PRP injection was $707 ± $388 (range, $175 to $4,973), and the mean cost of a SC injection was $2,728 ± $1,584 (range, $300 to $12,000). Practices offering PRP and SC injections tended to be larger (for PRP - 11.6 physicians per practice vs. 8.1, P<0.001; for SC - 12.3 vs. 9.7, P=0.006). In addition, practices that offered PRP injections were located in areas with higher mean income ($67,500 vs. $64,300, P=0.047). Variables associated with higher cost of PRP injection included city population (P<0.001) and mean income of residents (P<0.001). Conclusion: While the majority of sports medicine practices across the United States offer some type of orthobiologic injection, there exists significant variability in the cost of these injections. The cost for PRP injections is higher in practices located in highly populated areas and in areas with greater mean incomes.
Paper 41 Characterizing The Biological Constituents Of Platelet-poor Plasma--do The Platelets Matter? A Prospective Cohort Study Sandeep Mannava, MD, PhD1, Kaitlyn E. Whitney, BS2, Jillian King, BS2, Mitchell Kennedy, BS2, Grant Dornan, MS2, Jorge Chahla, MD, PhD2, Thos A. Evans, MD2, Johnny Huard, PhD3, Matthew T. Provencher, MD4, Robert F. LaPrade, MD, PhD4. 1University of Rochester, Rochester, NY, 2Steadman Philippon Research Institute, Vail, CO, 3University of Texas Health Science Center at Houston Medical School, Houston, TX, 4The Steadman Clinic, Vail, CO Objectives: Platelet-rich plasma (PRP) is comprised of several biologically active factors that can stimulate musculoskeletal healing processes. The supernatant of PRP, known as PPP, is biologically active and may also stimulate tissue regeneration. In some instances, such as muscle injury, PPP may be preferred to PRP in order to stimulate muscle regrowth in a basic science study that was previously performed. Platelet poor plasma (PPP) is has several biologically active molecular factors that may be utilized to stimulate tissue healing. While platelet rich plasma has been previously studied and characterized, few studies have sought to quantify the biological constituents of PPP. The purpose of this study was to quantitate and assess growth factors, other chemokines, and cytokines in PPP derived from human peripheral blood that has been centrifuged. Study Design:Non-randomized, prospective cohort study; Level of evidence: 2. Methods: Peripheral blood was drawn to create PPP at three time points from sixteen healthy volunteers. Hematology analysis was conducted on the PPP to quantify the platelet fold-difference from baseline measurements. The PPP samples were immediately assayed and analyzed on the MagPix®following processing completion. Specific immunoassay kits used were human cytokine/chemokine magnetic bead panel, TGF-β magnetic bead panel, MMP magnetic bead panel 1, and MMP magnetic bead panel 2. Results: Among the biological factors tested, there was a significant positive association, defined by two factors being associated in that when one factor increases the other also increases, between BMI and the biological composition of PPP with PDGF AA, PDGF AB, MMP-1, MMP-9, MMP-13, and MMP-12 (p<0.05). Similarly, there was a significant positive association (p<0.05), between age and biological composition of PPP for MMP-9 and MMP-7. Conclusion: PPP has several biological factors, both anabolic and catabolic, that can potentially be utilized in musculoskeletal medicine to treat various conditions, such as muscle injury. PPP is biologically active and this study characterizes its anabolic and catabolic profile. These factors are influenced by certain demographic factors such as age and body mass index (BMI). Higher BMI significantly correlated to higher levels of PDGF AA, PDGF AB, MMP-1, MMP-9, MMP-13, and MMP-12 in PPP. This supernatant
of the better-studied PRP is biological active and warrants further investigation for its therapeutic potential. Platelets could change the biological composition of plasma utilized for regenerative medicine applications, but this study demonstrates that the plasma alone has biological properties that may provide benefit in treating certain musculoskeletal conditions. This study will help clinicians better understand the biological nature of PPP and may aide in the more targeted use of PPP therapeutically.
Paper 42 Osteochondral Allograft Transplantation: Identifying the Biomechanical Impact of Using Shorter Grafts and Pulsatile Lavage on Graft Stability Jacob Babu, M.D.1, Jonathan D. Hodax, MD2, Paul D. Fadale, MD3, Brett D. Owens, MD4. 1Brown University Program, Providence, RI, 2University of California San Francisco Program, San Francisco, CA, 3University Orthopedic, Barrington, RI, 4Brown University Alpert Medical School, East Providence, RI Objectives: This study seeks to identify the ability of shorter Osteochondral Allografts (OCAs) to resist displacement/failure. Additionally, this study seeks to evaluate the effect of pulsatile lavage on the biomechanical stability of the OCA graft. Methods: Fifteen millimeter diameter, human cadaveric, osteochondral allografts of 4mm, 7mm, and 10mm in depth were harvested for comparison of resistance to compressive and tensile loads. For each group 7 specimens were subjected to tensile loads and 3 specimens subjected to compressive loads until failure (pull-out or subsidence). An additional study group of 10 pulsatile lavaged (PL) osteochondral allografts of 15mm in diameter and 7mm in depth were introduced for comparison to the original 7mm depth OCA group. Results: The average tensile forces for failure for the 4mm, 7mm, and 10mm plugs were 23.74N, 199.57N and 197.69N respectively (p=1.5x10-5). After post-hoc analysis of the tensile groups, significant differences in the mean tensile force to failure were appreciated between the 4mm and 7mm groups (p=4.12 x10-5) and the 4mm and 10mm groups (p=1.78x10-5), but not between the 7mm and 10mm groups (p=.9601). There were no significant differences between the average tensile forces resulting in failure for the 7mm and 7mm-PL groups (199.57N and 205.2N, p=.90) or compressive forces to failure respectively (733.6N and 656N, p=.7062). Conclusion: For OCAs of 15mm in diameter, a commonly used size in practice, we recommend that plugs of 7mm in depth be utilized. Pulsatile lavage of allografts prior to insertion does not appear to take away from the structural integrity and stability of the plug, however an adequately powered study should confirm this. With many described theoretical benefits of decreased immunogenicity and better long- term graft incorporation after lavage, we recommend that this practice continue.
Paper 43 Mesenchymal Stem Cells Delivered in a Novel Cartilage Mimetic Hydrogel for the Treatment of Focal Chondral Lesions in an Equine Animal Model Cecilia Pascual-Garrido, MD1, Francisco Rodriguez-Fontan2, Masahiko Haneda3, Elizabeth Aisenbrey, Researcher4, Karin Payne2, John David Kisiday, PhD5, Stephanie Bryant4, Laurie J. Goodrich, DVM, PhD5. 1Washington University School of Medicine, Saint Louis, MO, 2University of Colorado Denver, Aurora, CO, 3Washington University School of Medicine, St. Louis, MO, 4University of Colorado Boulder, Boulder, CO, 5Colorado State University, Fort Collins, CO Objectives: A degradable biomaterial has been developed that resembles the native cartilage biochemical properties, in which stem cells can be seeded, differentiate and develop cartilaginous tissue. The purposes of this study were: 1) to determine if mesenchymal stem cells (MSCs) embedded in this cartilage mimetic hydrogel display in vitro chondrogenesis; 2) to demonstrate that the proposed hydrogel can be delivered in situ; and 3) to determine if the hydrogel ± MSCs supports in vivo chondrogenesis. Methods: A photopolymerizable hydrogel consisting of polyethylene glycol, CVPLSLYSGC, chondroitin sulfate (ChS), CRGDS and TGF-β3 was used. Equine bone marrow-derived MSCs were encapsulated in the hydrogel and cultured for 9 weeks. Compressive modulus was evaluated at day 1 and at weeks 3, 6 and 9. Chondrogenic differentiation was investigated via qPCR, Safranin-O staining and immunofluorescence. Three female horses were used. Two 15-mm width x 5-mm depth osteochondral defects were created bilaterally in the medial femoral condyle of each stifle joint. Five groups were established: Hydrogel (n=3), Hydrogel + MSCs (n=3), Microfracture (MFX, n=1), MFX + Hydrogel (n=3), and MFX + Hydrogel + MSCs (n=2). Repair tissue was evaluated at 6 months post intervention with the following cartilage repair scoring systems: macroscopically, International Cartilage Repair Society (ICRS); and histologically, the Modified O’Driscoll scoring (MODS) and ICRS II (Overall assessment 0%, fibrous -100%, hyaline cartilage).The ICRS parameter is scored using a 100-mm VAS, a score of 0 was assigned for properties considered indicative of poor quality and 100 for good quality. Results: In vitro, there was a significant increase in compressive modulus, collagen II and ChS as confirmation of chondrogenesis and hydrogel degradation. (Figure 1) In vivo, the hydrogel was readily photopolimerized in the defect. Cartilage repair was evident in all groups. As shown in Table 1, red indicates best quality score, blue means a poor quality score, but there was no statistical difference. According to the macroscopic ICRS, the hydrogel + MSCs performed better (P= 0.47). However, the MFX + Hydrogel + MSCs tended to perform better per the MODS (P= 0.61); and ICRS-Overall assessment (P= 0.9). Particularly, MFX showed the lowest score for subchondral bone(SCB) abnormalities (0% = abnormal, P= 0.09) but no inflammation was evident (100% = absent, P= 0.53), whereas the Hydrogel had the highest basal integration (100% = complete integration, P= 0.38) but presented moderate inflammation (Figure 2A). MFX showed SCB abnormalities and vascularization (Figure 2 B). Interestingly, a defect treated with MFX + Hydrogel presented more GAGs, less inflammation (vs Hydrogel) and less
SCB abnormalities (vs MFX) (Figure 2C). Overall, the group performing better was MFX + Hydrogel + MSCs. Conclusion: This pilot study provides the first evidence of the ability to photopolymerize this novel hydrogel in situ and assess its ability to provide chondrogenic cues for cartilage repair in a large animal model. The presence of all three balanced factors (MFX, Hydrogel, MSCs) had higher scores per MODS summation and ICRS Overall assessment. Strengths of this study include: comparison of standard MFX therapy of osteochondral defects with a novel cartilage mimetic therapy; and use of a large animal that resembles the human knee biomechanically and anatomically.
Paper 44 Graft Thickness is Associated with Subchondral Cyst Formation in Patients After Osteochondral Allograft Transplantation in the Knee Jakob Ackermann, MD1, Gergo Merkely2, Nehal Shah3, Andreas H. Gomoll, MD4. 1Sports Medicine Center, Massachusetts General Hospital, Boston, MA, 2Sports Medicine, Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA, 3Brigham and Women's Hospital, Boston, MA, 4Hospital for Special Surgery/Cornell Medical Center Program, New York, NY Objectives: The purpose of this study was to determine potential predictive associations between preoperative patient characteristics or osteochondral allograft (OCA) morphology, and postoperative OCA appearance assessed by the osteochondral allograft magnetic resonance imaging scoring system (OCAMRISS) at 6-month follow-up. It was hypothesized that preoperative patient factors or OCA morphology are associated with postoperative OCAMRISS scores. Methods: This study evaluated 74 OCAs that were implanted in the femoral condyles of 63 patients for the treatment of symptomatic osteochondral defects in the knee.Postoperative MRI was obtained at an average follow-up of 5.5 ± 1.0 months. A musculoskeletal radiologist scored all grafts according to the OCAMRISS. Pearson’s correlation, Mann Whitney U test and chi-square test were used to distinguish associations between age, sex, smoker status, BMI, previous surgeries, concomitant surgeries, bone marrow augmentation, graft location, graft size, bony graft thickness, and OCAMRISS subscales. Results: At 6-month postoperative MRI evaluation, the mean OCAMRISS score was 3.9 ± 2 with 87.8% of OCAs presenting with crossing trabeculae indicating osseous integration, and 21.6% showing cystic formation of the graft and host-graft junction. When correlating patient and lesion characteristics with OCAMRISS subscales, following associations were identified: cartilage signal and age (p=0.021), subchondral bone plate congruity and bone marrow aspirate augmentation (p=0.046), cystic changes and bony graft thickness (p=0.019), opposing cartilage and prior surgery (p=0.045) and BMI (p=0.003), and synovitis and age (p=0.044) and positive smoking status (p=0.009). Osseous integration was not associated with any preoperative factor. Conversely, patient’s sex, OCA graft size and location did not correlate with any OCAMRISS subscale (p > 0.05). OCA bony thickness was the only plug-specific factor being associated with the OCAMRISS, and the only factor related to cystic formation at 6 months (p = 0.019). Grafts that presented with cystic formation were significantly thinner than grafts that did not show cystic changes at the host-graft junction (p = 0.008). Grafts with less than 5 mm bony thickness had an almost 5-fold increased risk of demonstrating cystic changes on MRI (odds ration [OR]= 4.9; 95% Confidence Interval [CI]= 1.5 - 16.1; p = 0.006). Conversely, OCAs thickness was not associated with osseous integration, except grafts with a bony thickness of more than 9 mm presented significantly more often with a discernible cleft than did shallower grafts (p = 0.049). Conclusion: Osteochondral allograft thickness is associated with subchondral cyst formation at short-term follow-up. Shallow grafts demonstrate a substantially increased risk of developing subchondral
cysts at the graft-host junction after OCA transplantation. Conversely, thicker grafts may negatively affect osseous graft integration. Hence, the authors suggest a bony graft thickness of 5-9 mm for OCAs to mitigate the risk of cystic formation and delay of osseous integration after cartilage resurfacing.
Relationship of Bony Osteochondral Allograft Thickness and Cystic Changes at 6 Months Postoperativel
Cystic Changes No Cystic Changes P Bony Graft Thickness, mm, Mean ±SD 4.9 ± 0.6 5.8 ± 1.6 0.008 Bony Graft Thickness under and over 5 mm, n 11 vs. 5 18 vs. 40 0.006
Paper 45 Early Weight-Bearing Improves Cartilage Repair in an in vitro Model of Microfracture:Comparison of Two Mechanical Loading Regimens on Simulated Microfracture Based onFibrin Gel Scaffolds Encapsulating Bone Marrow Mesenchymal Stem Cells Tomoya Iseki, MD1, Benjamin B. Rothrauff, MD PhD1, Shinsuke Kihara, M.D. PhD.1, Shinichi Yoshiya, MD2, Freddie H. Fu, MD1, Rocky S. Tuan, PhD1, Riccardo Gottardi, PhD1. 1University of Pittsburgh Medical Center, Pittsburgh, PA, 2Department of Orthopedic Surgery, Nishinomiya Hyogo, Japan Objectives: Microfracture of focal chondral defects produces fibrocartilage, which inconsistently integrates with the surrounding native tissue and possesses inferior mechanical properties compared to hyaline cartilage. Mechanical loading modulates cartilage during development, but it remains unclear how loads produced in the course of postoperative rehabilitation affect the formation of the new fibrocartilaginous tissue. The purpose of this study was to assess the influence of different mechanical loading regimens simulating weight-bearing or passive motion exercises on an in vitro model of microfracture repair based on fibrin gel scaffolds encapsulating mesenchymal stem cells (MSCs). Methods: Cylindrical cores were made in bovine hyaline cartilage explants and filled with either: (1) cartilage plug returned to original location (positive control), (2) fibrin gel (negative control), or (3) fibrin gel with encapsulated bone marrow-derived MSCs (BM-MSCs) (microfracture mimic). Constructs were then subjected to one of three loading regimens, including (1) no loading (i.e., unloaded) (2) dynamic compressive loading, or (3) rotational shear loading. On days 0, 7, 14, and 21, the integration strength between the outer chondral ring and the central insert was measured with an electroforce mechanical tester. The central core component, mimicking microfracture neotissue, was also analyzed for gene expression by real-time RT-PCR, glycosaminoglycan and dsDNA contents, and tissue morphology by histology. Results: Integration strengths between the outer chondral ring and central neotissue of the cartilage plug and fibrin + BM-MSC groups significantly increased upon exposure to compressive loading, compared to day 0 controls (p= 0.007). Compressive loading upregulated expression of chondrogenesis-associated genes (SOX9, collagen type II, and collagen type II:I, an indicator of more hyaline phenotype) in the neotissue of the fibrin + BM-MSC group, as compared to the unloaded group at day 21 (SOX9, p =0.0032; COL2A1, p <0.0001; COL2A1/COL1A1, p = 0.0308,). Fibrin + BM-MSC constructs exposed to shear loading expressed higher levels of chondrogenic genes as compared to the unloaded condition, but not as high as the compressive loading condition. Furthermore, catabolic markers (MMP3 and ADAMTS 5) were significantly upregulated by shear loading (p = 0.0234 and p< 0.0001, respectively) at day 21, as compared to day 0. Conclusion: Dynamic compressive loading enhanced neotissue chondrogenesis and maturation in a simulated in vitro model of microfracture, with generation of more hyaline-like cartilage and improved
integration with the surrounding tissue. Early weight-bearing after microfracture may be beneficial in promoting the formation of more hyaline-like cartilage repair tissue, whereas range of motion exercise by continuous passive motion without weight-bearing might not be as effective, or even negatively affect the formation of the repair tissue during post-surgery rehabilitation.
Paper 46 Two Year Clinical Outcomes of the Subchondroplasty® Procedure for Treatment of Symptomatic Bone Marrow Lesions of the Knee Christopher Hajnik, MD1, Sam Akhavan, MD2, Douglas J. Wyland, MD3, Steven B. Cohen, MD4, Laith M. Jazrawi, MD5, Thomas Youm, MD6, Gregory J. Loren, MD1, Jack Farr, MD7, Marianne Dornbush Rahme, Marianne Rahme8, Patrick Reischling9 1CORE Orthopaedic Medical Center, Encinitas, CA, 2Allegheny General Hospital, Pittsburgh, PA, 3Steadman-Hawkins Clinic of the Carolinas, Spartanburg, SC, 4Rothman Institute, Media, PA, 5NYU Hospital for Joint Diseases, New York, NY, 6RVC Orthopaedics PC, New York, NY, 7OrthoIndy South, Greenwood, IN, 8Zimmer Biomet, Warsaw, ID, 9Zimmer Biomet, Warsaw, IN Objectives: Bone Marrow Lesions (BML) are a common finding on knee MRI. In the knee, BML have a strong correlation to patient-reported pain, function, joint deterioration and rapid progression to TKR. Histologic analyses of BML have demonstrated findings consistent with fracture and bony remodeling of the trabeculae. The Subchondroplasty (SCP®) Procedure aims to treat the bone defects present in the BML by percutaneously filling them with a bone substitute material, designed to flow through intact bone, harden at body temperature and then heal through natural bone turnover. Previous retrospective, single-center case series have demonstrated improvements in patient-reported outcomes. The purpose of this prospective, multi-center study is to evaluate the 2-year clinical and radiographic outcomes of patients with BML of the knee treated with the Subchondroplasty Procedure. Methods: Seventy patients were treated between 2012 and 2017 for BML of the tibial plateau and/or femoral condyle. Self-drilling cannulas were inserted into the BML using arthroscopic and fluoroscopic guidance, then injected with AccuFill® Bone Substitute Material. All patients also underwent arthroscopy to aid in targeting the underlying bony lesion and address intra-articular pathology. MRIs and radiographs were obtained pre-operatively, at 6, 12 and 24 months, with additional radiographs collected at 6 weeks and 3 months. Patient-reported outcomes, including VAS pain, IKDC and KOOS were collected pre-operatively, 2 and 6 weeks, and 3, 6, 12 and 24 months post-operatively. Results: Seventy patients (36 males and 34 females), average age 57 were consented and enrolled in the study. Preoperative K-L grade included 1.4% Grade 0, 2.9% Grade 1, 27.1% Grade 2, 55.7% Grade 3 and 7.1% Grade 4. Fifty eight tibial plateaus and 41 femoral condyles were treated (29 bipolar lesions treated). VAS Pain scores improved from a mean of 6.2/10 pre-op to 2.9/10 at 1 year. IKDC scores improved from mean 33.9 pre-op to 61.3 at 1 year. KOOS scores improved from baseline to 1 year (Fig. 1) with mean KOOS Pain from 45.8 to 73.9, ADL 52.9 to 79.2, Symptoms 49.7 to 71.9, Sports 21.2 to 49.9 and Quality of Life 18.1 to 52.3. All patient-reported outcomes showed statistically significant improvement at one year. Two year outcomes collected to date appear to follow the same trend. The last study subject is due to return in January 2019 at which point the final 2 year analysis will be completed. Six patients (8.6%) converted to arthroplasty (1 UKA and 5 TKA) at one year. To date, the 24 month conversion rate is 16.1% out of 62 subjects. The final conversion rate for 24 months will be
calculated after the final subject returns. Radiographs and MRIs demonstrated good incorporation of the AccuFill material through 12 months with evidence of early remodeling and a lack of OA progression in the majority of subjects. Twenty-four month MRIs demonstrate continued remodeling of the AccuFill material. Conclusion: This study presents statistically and clinically-meaningful evidence of improvements in clinical outcomes following Subchondroplasty procedure for BML of the knee. The low conversion rate suggests this less-invasive procedure may delay the need for knee arthroplasty. MR imaging demonstrates good incorporation of the BSM and evidence of remodeling and reduction in material volume over time.
