Date of Completion

4-27-2016

Embargo Period

4-26-2016

Major Advisor

Yusuf Khan

Associate Advisor

Mei Wei

Associate Advisor

Lakshmi Nair

Associate Advisor

Jon Goldberg

Associate Advisor

Archana Sanjay

Field of Study

Materials Science and Engineering

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Each year approximately 600,000 and 2.2 million bone graft procedures are performed worldwide with 600,000 of them performed only in the United States. With a high success rate of osteo-integration and limited activation of the immune response, autografts are currently considered the gold standard for bone grafting. However, autografts are limited by the volume of bone tissue that can be harvested and by the threat of donor site morbidity. Allografts are alternatives to autografts since they are available in nearly unlimited supply and avoid donor-site morbidity and pain. However, allografts have been shown to be less frequently osteoinductive than autografts due to lack of biological factors, i.e., cells, growth factors. Limited vascularization, new bone formation and remodeling associated with large allograft healing are directly associated with clinical failure due to non-unions, late graft fractures and infections.

The objective of this thesis is to increase the functionality and subsequent incorporation of allograft into host bone by applying a thin polymeric coating to allografts that would be capable of carrying and delivering growth factors with quantitative precision in hopes of increasing the ability of allografts to heal large scale bone defects. It is hypothesized that loading the dual growth factors, bone morphogenetic protein-2 (BMP-2 ) and vascular endothelial growth factor (VEGF), onto a polymeric coating with two different techniques will result in short term and long term delivery kinetics. We also hypothesized that dual sequential delivery of BMP-2 and VEGF will show enhanced bone repair over BMP-2 delivered alone. We introduced a thin coating of poly(lactide-co-glycolide) (PLGA), that has been used for orthopaedic and

musculoskeletal applications, to functionalize rat femoral allografts. Allografts was coated and loaded with BMP-2 and VEGF independently and simultaneously using two different loading techniques, surface adsorption and encapsulation, each with distinct delivery kinetics. The rapid release of VEGF stimulated osteoclastogenesis and the sustained release of BMP-2 encouraged osteogenesis. The bioactivity of the growth factors, BMP-2 and VEGF was evaluated through different bioassays using Human Mesenchymal Stem Cells (hMSCs) and Bone Marrow Macrophages (BMMs), respectively. Healing of rat femoral segmental defect was assessed after 4 and 8 weeks to determine the effect of controlled release of VEGF and BMP-2.

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