1. Dr Mark Chong National University of Singapore Dept of Obstetrics and Gynaecology

2.  2 nd most transplanted tissue 1 million cases annually in US alone  Current treatment: Autograft: Site morbidity Allograft: Donor shortage, immune rejection  Solution: Tissue Engineering

3.  Resorbable scaffolds + osteogenic cells  Mature in bioreactor  TisXell System  Note: Function of bone is primarily structural  low hanging fruit Mesencymal stem cells (MSC)

4. Day 0 Day 14Day 28 Increased cellular proliferation Increased mineralisation TisXell

5. Day 0 Day 14Day 28 Increased cellular proliferation Increased mineralisation Increased viability Live Dead TisXell

7.  Created 7 mm defect  Press-fit 8 mm graft

10. S S S S S S

11.  TisXell stimulates bone formation 5.7 x more mineralisation than static  TisXell generated bone grafts are highly efficacious Rapid healing of fracture within 3 months vs non- union

12.  Minipig model  Larger volume, anticipate issues of vascularisation  Introduce endothelial progenitor cells (EPC) into cellular mix Mesencymal stem cells (MSC) Endothelial Progenitor Cells (EPC)

13.  TisXell supports co-culture of different cell types MSC EPC

14.  18 mm segmental defect in tibia  Monitor over 12 months: X-ray, CT, angiography

15. 1 mth3 mth fMSC-EPC 1 mth MSC

16. 1 mth3 mth fMSC-EPC 1 mth

17.  6 pigs implanted with TisXell cultured TEBG  All pigs survived; no adverse reaction  Mineralisation and bridging evident at 3 mths in MSC group; 1 mth in fMSC-EPC group  Studies to continue for long-term safety data (12 months)

18.  TisXell provides a controlled and conducive environment for generating TEBG implant  Potent osteo-stimulatory cues  Efficacy demonstrated in rat model  Potentially faster bone regeneration and vascularisation in minipig model  Preparatory work with clinicians for Clinical Phase I trial