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TisXell -Generated Bone Grafts – A Pre-clinical Study

TisXell -Generated Bone Grafts – A Pre-clinical Study. Dr Mark Chong National University of Singapore Dept of Obstetrics and Gynaecology. Why Bone?. 2 nd most transplanted tissue 1 million cases annually in US alone Current treatment: Autograft: Site morbidity

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TisXell -Generated Bone Grafts – A Pre-clinical Study

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  1. TisXell-Generated Bone Grafts – A Pre-clinical Study Dr Mark Chong National University of Singapore Dept of Obstetrics and Gynaecology

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

  3. How do we engineer Bone? Mesencymal stem cells (MSC) • Resorbable scaffolds + osteogenic cells • Mature in bioreactor  TisXell System • Note: • Function of bone is primarily structural •  low hanging fruit

  4. TisXell enhances bone formation Day 0 Day 14 Day 28 Increased cellular proliferation Increased mineralisation TisXell

  5. Bioreactor enhances bone formation Day 0 Day 14 Day 28 Increased viability Increased cellular proliferation Increased mineralisation TisXell Live Dead

  6. Bioreactor enhances bone formation TisXell

  7. Rat Femoral Defect model Created 7 mm defect Press-fit 8 mm graft

  8. CT scans show bridging AND mineralisation

  9. Healing in TEBG group; non-union in control

  10. S S S S S S Mineralisation confirmed by histology

  11. Findings from rodent studies • 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. Scaling up Mesencymal stem cells (MSC) Endothelial Progenitor Cells (EPC) Minipig model Larger volume, anticipate issues of vascularisation Introduce endothelial progenitor cells (EPC) into cellular mix

  13. Cells remain viable and randomly distributed  TisXell supports co-culture of different cell types MSC EPC

  14. Minipig Critical-Size Defect Model • 18 mm segmental defect in tibia • Monitor over 12 months: • X-ray, CT, angiography

  15. Computed Tomography (CT) shows bridging at 3 months fMSC-EPC 1 mth 3mth 1 mth MSC

  16. CT Angiography: rapid vascularisation of fMSC-EPC group MSC fMSC-EPC 1 mth 3mth 1 mth

  17. Findings so far… 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. Conclusion 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

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