Development of a novel No disclosures. self-assembling bone graft - - PowerPoint PPT Presentation

5/8/2014 1

Development of a novel self-assembling bone graft substitute

Yijia (Helena) Hong Alan Dang Lab Orthopaedic Research Group San Francisco VA Medical Center

DISCLOSURES

No disclosures.

THE PROBLEM

Current commonly used bone grafts: Autologous bone graft Recombinant bone morphogenetic proteins (BMPs) Scaffolds (demineralized bone matrix, ceramics)

THE PROBLEM

Current commonly used bone grafts: Autologous bone graft

Osteogenic Effective 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)

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THE PROBLEM

Current commonly used bone grafts: Autologous bone graft Recombinant bone morphogenetic proteins (BMPs)

Osteoinductive Effective Readily available Difficult to control

Swelling in the C-Spine Heterotopic ossification Inflammation

Associated with cancer

Scaffolds (demineralized bone matrix, ceramics)

THE PROBLEM

Current commonly used bone grafts: Autologous bone graft Recombinant bone morphogenetic proteins (BMPs) Scaffolds (demineralized bone matrix, ceramics)

Osteoconductive Probably safer than BMPs Less effective

THE PROBLEM

Current bone grafts and bone graft substitutes: Experience struggle between efficacy and safety All generate “fusion mass” instead of structured bone

OUR GOAL

Develop a new bone graft substitute: Osteogenic Requires no exogenous BMPs Highly controllable

Reproducibly generate structured bone Control shape and dimensions of bone formed by graft

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OUR HYPOTHESIS

An osteogenic bone graft substitute capable of forming structured bone and controlling bone shape and dimension can be developed using 1) MSCs and 2) a gelatin scaffold (Gelfoam) in a murine model.

1 C57BL/6J donor mouse Harvest femur and tibia Extract bone marrow Expand and differentiate in vitro Seed gelatin sponge with cells Implant 2 C57BL/6J host mouse Mesenchymal stem cells Osteoblasts

Small block Beam Cylinder Torus 1 2 3 4

3mm

Self-assembly

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Photo credit to Pooja Desai

Immediately after seeding sponge with cells 8 weeks postoperative

How well can we shape and structure the bone?

Week Small block Beam n = 8 n = 3 4 8 12

1 2 3 4 5mm

beam block

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1 2 3 4 5mm

Week Cylinder Torus n = 3 n = 3 4 8 12

Rounded shapes:

Produced less structured bone Conformed to scaffold geometry only to a limited extent

What about strength of bone?

500 1000 1500 2000 2500 3000 3500 4000

Small block Cylinder Torus Beam Radiodensity (Hounsfield Units)

Cortical bone radiodensity at 4 weeks and 8 weeks across scaffold geometries

4wk cortical 8wk cortical

* * *

• 1000

1000 2000 3000 4000 5000 6000 7000 8000

Radiodensity (Hounsfield Units) Type of bone

Cortex Marrow Cortex Marrow Cortex Marrow

Engineered bone Vertebrae Femur

Comparison: Radiodensities of cortex and cancellous bone across different types of bone

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CONCLUSIONS

Our bone graft substitute: Self-assembles in 1-2 months 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

FUTURE DIRECTIONS

Fusing of two separate blocks

Photo credit to Pooja Desai Cross section: Side view:

ACKNOWLEDGEMENTS

Members of the Orthopaedic and Endocrine research groups at San Francisco VAMC Pooja Desai, BS Alan Dang, MD Bernard Halloran, PhD

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THANK YOU FOR YOUR ATTENTION

1 2 4 3

Photo credit to Pooja Desai for postoperative 8 week ex vivo sections.

Before After

Week Small block Beam Cylinder Torus n = 8 n = 3 n = 3 n = 3 4 8 12

1 2 3 4 5mm