The document describes an innovative AMCA BoneCure membrane for bone regeneration and fracture healing. Key points: - The AMCA membrane is biocompatible, sterile, and manufactured under GMP. It is micro porous and flexible. - Preclinical studies in rabbits and sheep showed the membrane provides an optimal environment for rapid fracture healing by acting as a barrier, osteoconductive scaffold, and carrier for drugs/stem cells. Membrane treated fractures healed fully while untreated gaps did not. - Case studies in dogs and cats demonstrated accelerated healing times of 3-6 weeks for fractures treated with the membrane compared to expected healing times of 3-12 months. Histology confirmed new bone formation in membrane treated

1. INNOVATIVE MEMBRANE FOR BONE REGENERATION &
FRACTURE HEALING
November 2011
Confidential

2. The Product: AMCA BoneCure™ Membrane
Characteristics
 Sterile & Pyrogen free AMCA (Ammonio
Methacrylate Copolymer type A) membrane polymer;
 Biocompatible- 6 months studies, ISO
10993-1 Biological evaluation of medical
devices – Part 1;
 Manufactured under GMP conditions in
clean room;
 Physical Properties:
Thickness – 350 µm (±15%)
Flexible & strong, tensile strength 4 - 8 Mpa
Micro porous (11%), pore size 0.2 – 1.6 µm
Moisture content <1.5%

3. REGENECURE Solution for Fracture Repair: Regenerative
Membrane Implant
• AMCA membrane provides optimal conditions for
rapid & natural fracture healing:
√ Barrier – provides protected healing space,
retains cells & growth factors;
√ Osteoconductive scaffold that supports
Mesenchyemal Stem Cells (MSC) :
Adherence
Proliferation
Differentiation of MSC into bone tissue
√ Promotes Guided Bone Regeneration (GBR);
 Effective carrier for drugs and MSC;

4. Preclinical Rabbit Study: AMCA BoneCure vs. Bone Void Filler
Study Protocol:
Implantation of BoneCure
• 11 male New Zealand rabbits underwent
midshaft resection of radial bone (1cm in
length);
• 4 rabbits - tubular BoneCure membranes
were implanted;
• 4 rabbits - SYNTHES Bone Void Filler Granules
were implanted;
• 3 rabbits – control, no treatment;
Bone Void Filler Implantation
• Safety evaluation;
• Evaluation of fracture healing process –
lateral radiograph 2 – 8 weeks
postoperatively,
total area of the new bone formed was
calculated;
• 8 weeks post surgery – animals were
sacrificed, histological evaluations were
performed;

5. Preclinical: 8 Weeks Post Implantation
SYNTHES bone void
No treatment BoneCure membrane
filler implant
Gap is not bridged Gap is bridged Gap is not bridged

6. Micro CT- 8 W Post Implantation
No treatment BoneCure membrane SYNTHES bone void
filler implant

7. Histological Evaluation – Radiograph & Scanned Slides of the Specimens
No treatment BoneCure Membrane BVF – HA Granules

8. Preclinical: Sheep Study In Critical Size Model
Study Protocol:
BoneCure membrane being implanted, in critical size defect
• Segmental defect in the Tibia
(3.5 cm in length);
• 8 sheep - tubular BoneCure
membranes were implanted;
• 8 sheep - SYNTHES BVF Granules
were implanted;
• Safety evaluation;
• Evaluation of fracture healing
- total area of the new bone formed
was calculated;
- 16- 24 weeks post surgery –
animals will be
sacrificed, histological evaluations
will be performed

9. AMCA Membrane Supports Cells Adhering and Spreading in
Spindle Like Shape
Scanning electron microscopy of human mesenchymal stem cells upon AMCA membrane

10. Case study no 100-01: 5 years Old St. Bernard
with Comminuted Fracture of the radius, ulna.
Cranio medial approach to the radius expo
Time Zero 3 weeks post surgery 6 weeks post surgery
Healing time 3 weeks (average healing time 3 months)

11. • Medical Procedure of the 5 yr. old St. Bernard:
 A 5 years old spayed St. Bernard female.
 Comminuted fracture of the Radius and Ulna
 Cranio medial approach to the radius; exposure of the proximal and
• distal fracture edges.
 BoneCure® membrane was placed from the top and surrounded about
• 270 degrees of the circumference of the radius.
 The BoneCure ® membrane was tucked under the muscles and sutured
• to them along its length.
 Routine closure. Insertion of 3 smooth IM pins in a Type ll
• configuration (Uniplanar bilateral) with acrylic bars to support the
• frame.
 Bandaging of the leg for 7 days.

12. Case study no 102-003: S-A dog, female.
Fracture of femur.
•: A 5 years old spayed St. Bernard female. Post – op.
Post – op. 4 weeks 7 weeks Post – op.
•Comminuted fracture of the Radius and Ulna,
• caused probably by a low energy, heavy weight (Jeep wheel) passing over the leg.
•Cranio medial approach to the radius; exposure of the proximal and distal fracture
edges.
• The membrane was placed from the top and surrounded about 270 degrees of the
circumference of the radius.
• It was tucked under the muscles and sutured to them along its length. Routine
closure. Insertion of 3 smooth IM pins in a Type ll configuration (Uniplanar bilateral)
with acrylic bars to support the frame. Bandaging of the leg for 7 days.

13. Case study 001-006 (chello)
Post – op. 3 weeks Post – op. 6 weeks Post – op.
•: A 5 years old spayed St. Bernard female.
•Comminuted fracture of the Radius and Ulna,
• caused probably by a low energy, heavy weight (Jeep wheel) passing over the leg.
•Cranio medial approach to the radius; exposure of the proximal and distal fracture
edges.
• The membrane was placed from the top and surrounded about 270 degrees of the
circumference of the radius.
• It was tucked under the muscles and sutured to them along its length. Routine
closure. Insertion of 3 smooth IM pins in a Type ll configuration (Uniplanar bilateral)
with acrylic bars to support the frame. Bandaging of the leg for 7 days.

14. Medical Procedure of 3 mo. Old Dog with suspected OI Disease
• A 3 months old mixed breed male.
• Comminuted fracture of the femur (while playing with owners at home, on a
slippery floor).
• Initially NOT a candidate for BoneCure, but during the operation bones were
splitting to the weakest of handling, and it was thought that any extra help would
be in place. Hence the membrane was used.
• It appeared post op that the pup comes from a litter of 7, 4 of which have suffered
low velocity fractures such as itself. A bone sample from his sister was analyzed
histologically by a qualified veterinary pathologist and was found to suffer from
Osteogenesis Imperfecta (O.I.)
• Six weeks post op. the puppy is doing well and the bone seems to be healing in
time
• Average Healing time- 4-6 wk. in a healthy puppy.

15. Case study no Le chat
Post – op. 3 weeks Post – op 6 weeks Post – op
•: A 5 years old spayed St. Bernard female.
•Comminuted fracture of the Radius and Ulna,
• caused probably by a low energy, heavy weight (Jeep wheel) passing over the leg.
•Cranio medial approach to the radius; exposure of the proximal and distal fracture
edges.
• The membrane was placed from the top and surrounded about 270 degrees of the
circumference of the radius.
• It was tucked under the muscles and sutured to them along its length. Routine
closure. Insertion of 3 smooth IM pins in a Type ll configuration (Uniplanar bilateral)
with acrylic bars to support the frame. Bandaging of the leg for 7 days.

16. Medical Procedure in a 4yr. Old, Cat, DSH
 A 4 years old DSH cat, that fell off the 4th floor (High Rise Syndrome).
 Comminuted fracture of the femur
 No attempt was made to reduce the fragments with cerclage wires, rather the
membrane was wrapped around the whole area
 after an IM pin was introduced into the bone.
 Averege healing time - 7-12 wk.

17. Case study no Wassily
Post – op. 3 weeks Post – op 6 weeks Post – op
•: A 5 years old spayed St. Bernard female.
•Comminuted fracture of the Radius and Ulna,
• caused probably by a low energy, heavy weight (Jeep wheel) passing over the leg.
•Cranio medial approach to the radius; exposure of the proximal and distal fracture
edges.
• The membrane was placed from the top and surrounded about 270 degrees of the
circumference of the radius.
• It was tucked under the muscles and sutured to them along its length. Routine
closure. Insertion of 3 smooth IM pins in a Type ll configuration (Uniplanar bilateral)
with acrylic bars to support the frame. Bandaging of the leg for 7 days.

18. Medical Procedure of 4 yr. old Dog
 A 4 years old Chinese Poodle
 Simple, distal third fracture of the Radius and Ulna
 NOT a comminuted fracture, but as it appears in a size of dogs (breed) known to
suffer from higher than average non unions, it was decided that in addition to a
plate, the membrane will be used.
 A 2.7 mm DCP was used, with 7 screws.
 The fracture in the radius (under the plate) seems to be totally healed in 6
weeks, while the ulnar fracture is completing the process albeit a little behind the
radius.
 Average healing time - The expected time to healing under a plate in a mature
skeleton is 5 - 12 months.

19. Case study no 2: Nuredin Dog - 6mo.
M-fracture of femur left side
Post – operational X- 11 weeks Post –
ray. The gap is operational X-ray. The
evident gap is closed. Yet, the Gap
edges are seen

20. Scanned from:
1. Denny HR, Butterworth SJ. Fracture Healing. In: A Guide to Canine and
Feline Orthopaedic Surgery. Blackwell Science Ltd; 2008. p. 1–17.

21. •: A 5 years old spayed St. Bernard female. & Feline study:
Interim analysis of Canine
•Comminuted fracture of the Radius and Ulna,
• caused probably by a low energy, heavy weight (Jeep wheel) passing over the leg.
• The purpose to the radius; To evaluate the safety, performance and
•Cranio medial approachof the study is:exposure of the proximal and distal fracture
edges. initial efficacy of a guided bone regeneration membrane.
• The membrane was placed from the top and surrounded about 270 degrees of the
•12 of the skeletally dogs and cats, enrolled during (01-
circumferencematureradius.
04/12), suffering from:
• It was tucked under the muscles and sutured to them along its length. Routine
3 radius/ulna fracture
closure. Insertion of 3 smooth IM pins in a Type ll configuration (Uniplanar bilateral)
5 femural fractures
with acrylic bars to support the frame. Bandaging of the leg for 7 days.
2 pancarpal artrodesis fracture
2 humeral condyl fracture
• Out of 12 patients 4 were enrolled during the first 2 months the other
8 were enrolled during the last two months, currently 11 out of 12 pt.
show clinical improvement in their medical condition and quality of life

22. •: A 5 years old spayed St. Bernard female.
•Comminuted fracture of the Radius and Ulna,
13
• caused probably by a low energy, heavy weight (Jeep wheel) passing over the leg.
12
11
•Cranio medial approach to the radius; exposure of the proximal and distal fracture
10
edges. 9
Number of patients
8
• The membrane was placed from the top and surrounded about 270 degrees of the
7
circumference of the radius.
6
5
• It was tucked under the muscles and sutured to them along its length. Routine
4
closure. Insertion of 3 smooth IM pins in a Type ll configuration (Uniplanar bilateral)
3
2
with acrylic bars to support the frame. Bandaging of the leg for 7 days.
1
0
clinical improvement gap bridging
improved non changed

23. –