tisxell -generated bone grafts – a pre-clinical study

Dr Mark ChongNational University of Singapore

Dept of Obstetrics and Gynaecology

2nd most transplanted tissue• 1 million cases annually in US alone

Current treatment:• Autograft: Site morbidity• Allograft: Donor shortage, immune rejection

Solution: Tissue Engineering

Resorbable scaffolds + osteogenic cells

Mature in bioreactor TisXell System Note:

• Function of bone is primarily structural low hanging fruit

Mesencymal stem cells

(MSC)

Day 0 Day 14 Day 28

Increased cellular

proliferation

Increased mineralisationT

isXell

Day 0 Day 14 Day 28

Increased cellular

proliferation

Increased mineralisation

Increased viability

LiveDead

TisXell

TisXell

Created 7 mm defect Press-fit 8 mm graft

SS

S

S

S

S

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

Minipig model Larger volume, anticipate issues of

vascularisation Introduce endothelial progenitor cells

(EPC) into cellular mix

Mesencymal stem cells

(MSC)

Endothelial Progenitor Cells (EPC)

TisXell supports co-culture of different cell types

MSCEPC

18 mm segmental defect in tibia Monitor over 12 months:

• X-ray, CT, angiography

1 mth

3 mth

fMSC-EPC

1 mth

MSC

MSC

1 mth

3 mth

fMSC-EPC

1 mth

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)

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