5/8/2014 DISCLOSURES Development of a novel No disclosures. self-assembling bone graft substitute Yijia (Helena) Hong Alan Dang Lab Orthopaedic Research Group San Francisco VA Medical Center THE PROBLEM THE PROBLEM Current commonly used bone grafts: Current commonly used bone grafts: � Autologous bone graft � Autologous bone graft � Osteogenic � Recombinant bone morphogenetic proteins (BMPs) � Effective � Scaffolds (demineralized bone matrix, ceramics) � Safe � Requires extra procedure � Donor site morbidity and pain � Patient to patient variability � Not a “renewable resource” � Recombinant bone morphogenetic proteins (BMPs) � Scaffolds (demineralized bone matrix, ceramics) 1
5/8/2014 THE PROBLEM THE PROBLEM Current commonly used bone grafts: Current commonly used bone grafts: � Autologous bone graft � Autologous bone graft � Recombinant bone morphogenetic proteins (BMPs) � Recombinant bone morphogenetic proteins (BMPs) � Osteoinductive � Scaffolds (demineralized bone matrix, ceramics) � Effective � Osteoconductive � Readily available � Probably safer than BMPs � Difficult to control � Less effective � Swelling in the C-Spine � Heterotopic ossification � Inflammation � Associated with cancer � Scaffolds (demineralized bone matrix, ceramics) THE PROBLEM OUR GOAL Develop a new bone graft substitute: Current bone grafts and bone graft substitutes: � Osteogenic � Experience struggle between efficacy and safety � Requires no exogenous BMPs � All generate “ fusion mass ” instead of structured bone � Highly controllable � Reproducibly generate structured bone � Control shape and dimensions of bone formed by graft 2
5/8/2014 OUR HYPOTHESIS Extract bone Harvest femur marrow and tibia 1 C57BL/6J donor Mesenchymal mouse stem cells An osteogenic bone graft substitute capable of Expand and differentiate in vitro forming structured bone and controlling bone shape and dimension can be developed using 1) Seed gelatin MSCs and 2) a gelatin scaffold (Gelfoam) in a sponge with cells Implant 2 murine model. Osteoblasts C57BL/6J host mouse 1 Small block 3mm 2 Beam Self-assembly 3 Cylinder 4 Torus 3
5/8/2014 Immediately after seeding 8 weeks postoperative sponge with cells Photo credit to Pooja Desai How well can we shape and structure the bone? Week Small block Beam n = 8 n = 3 beam block 4 8 12 1 2 3 4 5mm 4
5/8/2014 Week Cylinder Torus n = 3 n = 3 � Rounded shapes: 4 � Produced less structured bone � Conformed to scaffold geometry only to a limited extent What about strength of bone? 8 12 1 2 3 4 5mm Comparison: Cortical bone radiodensity at 4 weeks and 8 weeks Radiodensities of cortex and cancellous bone across different types of bone across scaffold geometries 8000 * * * 4000 Radiodensity (Hounsfield Units) Radiodensity (Hounsfield Units) 7000 3500 6000 3000 5000 2500 4000 2000 3000 1500 2000 1000 1000 500 0 0 -1000 Small block Cylinder Torus Beam Engineered bone Vertebrae Femur 4wk cortical 8wk cortical Cortex Marrow Cortex Marrow Cortex Marrow Type of bone 5
5/8/2014 CONCLUSIONS FUTURE DIRECTIONS Fusing of two separate blocks Our bone graft substitute: � Self-assembles in 1-2 months Cross section: Side view: � Stable size and shape in 1-2 months � Good control of size in rectangular shapes � Reasonable bone density in relation to native bone � Requires no exogenous BMPs Photo credit to Pooja Desai ACKNOWLEDGEMENTS Pooja Desai, BS Alan Dang, MD Bernard Halloran, PhD Members of the Orthopaedic and Endocrine research groups at San Francisco VAMC 6
5/8/2014 THANK YOU FOR YOUR ATTENTION Week Small block Beam Cylinder Torus n = 8 n = 3 n = 3 n = 3 Before 4 4 3 8 1 After 2 12 1 2 3 4 5mm Photo credit to Pooja Desai for postoperative 8 week ex vivo sections. 7
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