SYNTHETIC HIGH PURITY CaSO4

Stimulan® implant grade calcium sulphate is a synthetic biocompatiblebone graft material that completely resorbs, to be replaced by newbone. It has a rate of resorption that corresponds with the rate ofnew bone growth.

Stimulan® calcium sulphate is produced using a proprietarysynthetic process# ensuring consistent and reproducible results.The physical and chemical properties are tightly controlled with notraces of potentially toxic impurities, which have been associatedwith naturally occurring mineral sources of calcium sulphate.

Stimulan® represents a major breakthrough in resorbable bonegraft technology. In terms of purity and consistency, it is unrivalledby virtue of its unique and proprietary process, which has beendeveloped by Biocomposites’ biomaterial development team overyears of careful, in-depth research.

AVAILABLE IN 3 FORMS

PELLETSAbsorbable pellets for open procedure

PERCUTANEOUS DISPENSERFor minimally invasive procedure

INJECTABLE PASTEFully setting paste with individual pelletising kit

# International Patents Pending

BONE GRAFTING THE FUTURE

page 2

The Case for Synthetic Bone Substitutes

Autograft

Autograft availability is limited and its harvesting, usually from the iliaccrest, increases surgery time, can prolong hospital stay and very oftenresults in donor site morbidity.

“...tissue banks vary in complexity and scope of operation anddepend on a variety of techniques in the selection of donors andthe exclusion and preparation of bone and tissue allografts...”

“...therefore it behoves orthopaedic surgeons to find outspecifically how the allografts they are about to use were excisedand prepared...”

“...irradiation clearly alters biomechanical properties of collagen,hence bone structure, and diminishes its osteoinductive potential...”

Extracts taken from - Bone Loss in Revision Surgery: How to Manage the Femoral Side.

C.A. Engh, Sr., W.C. Head, A.G. Rosenberg, F.H. Sim

American Academy of Orthopaedic Surgeons 68th Annual Meeting, 2001.

AllograftGalea et al stated that the source from bone banks cannot meetthe demand for the increasing incidence of revision surgery.

J Bone Joint Surgery (Br) Vol. 80-B No. 4, July 1998

Palmer et al referred to their findings of pathological lesions presentin osteoarthritic femoral heads; unknown to both the patient andthe medical staff.

J Bone Joint Surgery (Br) Vol. 81-B No. 2, March 1999

Bone grafting techniques have been widely used in orthopaedicsurgery and bone is the second most frequently transplantedmaterial after blood. Bone grafts are increasingly used to fill bonecavities resulting from disease, trauma or surgery and also to fusejoints and non-unions.

Specification of Stimulan®

Comparison Table - Competitor Products

Nd Not detected

* The earth mineral, dolomite

** Aggregate, or “earth impurities” are present in calcium sulphate sourced from mined

gypsum rock. They are non-bioabsorbable and can include such elements as feldspar, clay and crystalline

silica (quartz)

Controlled phase purity ensures consistent resorption

Higher chemical purity ensures total biocompatibility

The resorption rate is consistent with the formationof new bone

Safe to use even in infected cases

Key advantages to the Surgeon

Stimulan® productgeometry and form

Presentation to surgical siteCalcium sulphatechemical form

Injectable, mouldable,setting paste

Dispenser for percutaneous,minimally invasive

implantation or in jars

Hemihydrate

Di-hydrate

Powder andmixing solution

Preformed, uniformpellets

Phase analysis

CaSO4 2H2O

CaCO3MgCO3*

CaCO3

Aggregate**

Commercialcalcium sulphate

80-94%>

5.1%

1.0%

4.5%

Medical/surgicalgrade

98%>

0.5%

0.3%

0.3%

Stimulan®

implant grade

100%

Nd

Nd

Nd

SpecificationCharacteristic

Chemical

Physical

Purity

CaSO4 2H2O

Regular pellets or injectable setting paste

100%

page 3

TECHNICAL PROFILE

BONE REGENERATION THE EVIDENCE

page 4

Figure 1

Trabecular bone interspersed with healthy bone marrow - sheep study

In-vitro Studies - Scanning electron micrograph showing human osteoblasts growing onsurface of Stimulan® at 21 days

In-Vitro Studies - Stimulan®

In-Vivo Studies - Stimulan®

Stimulan® calcium sulphate pellets were implanted into a sheep’s

epiphyseal humerus.

Radiographic examination 6 weeks after implantation shows no

evidence of the pellets, indicating complete resorption

Trabecular bone can be clearly seen interspersed with healthy bone

marrow (Figure 1) and osteoblast activity is much in evidence (Figure 2).

Figure 2

Osteoblasts at 6 weeks in a sheep model

Stimulan® Calcium Sulphate

Osteoblast

Stimulan® Calcium Sulphate

Trabecular Bone

Bone Marrow

Osteoblasts

* Full data available on request from Biocomposites

Single cell layer ofosteoblasts on surfaceof new bone - indicatingremodelling activity

Newly formedtrabecular bone

page 5

CASE STUDYMA/SK090106

53 year old male sustained comminuted distaltibial fracture

Normal physiologic absorption of CaSO4 occurs with thesimultaneous deposition of autogenous cancellous bone

Andries S. Coetzee, Mmed (ORL) Arch Otolaryngol-Vol.106, July 1980

Calcium Sulphate is the material of choice when infectionis present or anticipated

Leonard F. Peltier, M.D. Professor of Surgery, University of Kansas Medical Centre, Kansas City,

Kansas - The Use of Plaster of Paris to Fill Defects in Bone, Clin Orthop 21-31, 1961

Stimulan® placed usingposterior approach withdecortication andreconstruction of articularsurface

8 weeks post op showingadvanced resorptionwith healing and callusformation

18 months post opshowing total resorptionand advanced healing

Reduction of ankle fracture fragments was achieved using Stimulan®

to maintain space and promote ingrowth of new bone

Indications Pot Size/Dosage

Catalogue RefDiaDispenser/Cannula

Spinal Fusion

Trauma

Benign Cystic Lesions

Revision Surgery

Diabetic Foot

3.0mm

4.8mm

5cc

10cc

10cc

20cc

600-30-005

600-30-010

600-48-010

600-48-020

Absorbable pellets for openprocedure

SYNTHETIC HIGH PURITY CaSO4

PelletsCLINICAL EVIDENCE

Calcium Sulphate is an outstanding bone substitute ensuring boneformation and gives results comparable with autogenous bone

Andries S. Coetzee, Mmed (ORL) Arch Otolaryngol-Vol.106, July 1980

page 6

CASE STUDYMA/SK100106

10 year old male with femoral cyst

Femoral cyst below the lesser trochanter, previous treatment of thecyst involved cortisone injections. However, the hole left by theneedle in the cortex caused the femur to fracture.

Fracture was treated with Stimulan® pellets placed percutaneously.

The patient was reviewed at 14 weeks and the X-rays showcomplete resorption and new bone formation.

Femoral cyst, 10 year old malePrevious treatment failed

Intra-operative placement ofStimulan® using dispensers

14 week follow up showingtotal resporption and newbone formation

ProductsPot Size/Dosage Catalogue RefDia

Dispenser/Cannula

Stimulan® Dispensers 3.0mm

4.8mm

1.5cc

5cc

3mm

4.8mm

600-30-s1

600-48-s1

650-C3

650-C2

650-001Sterilisation Tray

SYNTHETIC HIGH PURITY CaSO4

Dispenser

Percutaneous dispenser (1.5cc & 5cc)

for minimally invasive procedure

Stimulan® Instrument Set

Cannulas instrumentation set to aiddispenser insertion

CLINICAL EVIDENCE

page 7

CASE STUDYMA/SK170106

80 year old male with spinal stenosis

Fusion of Lumbar vertebral interbodies (L2-L5) was achieved usingStimulan® in combination with autograft

ProductPot Size/Dosage Catalogue RefDia

Dispenser/Cannula

Stimulan® Kit 5cc 600-005

Fully setting injectable pastewith individual pelletising kit

SYNTHETIC HIGH PURITY CaSO4

Kit

An injectable and mouldable matrix which sets at body temperatureand fully resorbs to be remodelled by new bone.

Pack Contents Disposable

• CaSO4 • Pre-measured mixing solution bulbs • Syringe• 8cm Extension Tube • Pellet Mould • Spatula

Stimulan® Preparation Protocol for Syringe Injection

Post-opStimulan® placed in combination withautograft

9 months post-opTotal resorption of Stimulan®. New bonegrowth and fusion of Lumbar Vertebrae.L2-L5.

CLINICAL EVIDENCE

10cc 600-010

Step 1 Step 2 Step 3 Step 4 (i) Step 4 (ii)

Step 1 Empty powder into a sterile mixing bowl.

Step 2 Slowly add mixing solution from both bulbs. (If application to pellet mould with spatula is preferred, use contents of large bulb only)

Step 3 Mix thoroughly until a smooth paste is formed (approximately 30 seconds).

Step 4 (i) Backfill the syringe with the paste. Attach the extender tube if required.

(ii) The paste can then be injected into the surgical site.

Please note the kit starts to set hard 3 minutes after mixing and will becomedifficult to draw through the syringe after this time.

Step 5 Allow digitally packed or injected paste to cure undisturbed for 15 minutes after mixing prior to closure.

page 8

BIBLIOGRAPHY

M R Urist:Bone Transplants and Implants, In: Fundamental and Clinical Bone Physiology(Urist M R Editor) pp 331-368, 1980 

L F Peltier, D P Speer:   Calcium Sulphate. In: Bone Grafts and Bone Substitutes(M B Habal and A H Reddi, eds) pp. 243-251, 1993 

A S Coetzee:Regeneration of Bone in the Presence of Calcium Sulphate. Arch. Otolaryngol.106: 405-409, 1980 

D Robinson, D Alk, J Sandbank, R Farber, N Halperin:Dept. of Orthopaedics, Assaf Harofe Medical Centre, Zefferin, Israel.Ann Transplant 1999; (3-4):91-7 

L F Peltier:The Use of Plaster of Paris to Fill Large Defects in Bone.Am. J. Surg 97(3): 311-315,1959 

I S DeWet, C Jansen:The Use of Plaster of Paris to Fill Large Defects in Bone.South African J. Surg. 11: 1-8, 1973 

W R Walsh PhD, P Morberg MD PhD, Y Yu PhD, J L Yang PhD,W Haggard PhD, P C Sheath MBBS, M Svehla PhD, W J M Bruce MBBS:Response of a Calcium Sulfate Bone Graft Substitute in a Confined CancellousDefect. Clinical Orthopaedics and related research, 406: pp. 228-236, 2003 

R Mirzayan MD, V Panossian MD, R Avedian BS, D M ForresterMD, L R Menedez MD:The Use of Calcium Sulfate in the Treatment of Benign Bone Lesions –a Preliminary Report JBJS vol. 83-A No. 3 March 2001 

D G Armstrong et al:The Use of Absorbable Antibiotic-impregnated Calcium Sulphate Pellets in theManagement of Diabetic Foot Infections. Diabetics UK, Diabetics Medicine vol.18 pp 937-943, 2001 

R Strocchi et al:Bone Regeneration with Calcium Sulphate: Evidence for Increased Angiogenesisin Rabbits. Journal of Oral Implantology vol. 28 no. 6 pp 273-278, 2002 

A G Hadjipavlou MD, J W Simmons MD, J Yang MD, C L Nicodemus PhD,O Esch MD, D J Simmons PhD:Plaster of Paris as an Osteoconductive Material for Interbody Vertebral Fusion inMature Sheep. Spine vol. 25 no. 1 pp 10-16, 2000 

T A Wichelhaus et al:Elution Charateristics of Vancomycin, Teicoplanin, Gentamycin and Clindamycinfrom Calcium Sulphate Beads. Journal of Antimicrobial Chemotherapy, 2001 

B Meng-Hai et al:An Implant of a composite of Bovine Bone Morphogenetic Protein and Plasterof Paris for Treatment of Femoral Shaft Nonunions. Int Surg,81:pp 390-392, 1996

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