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theses

Bone loss and skeletal deficiencies due to traumatic injury or disease are major problems worldwide. In the U.S., approximately 500,000 bone-grafting procedures are performed annually. The main replacement options for bone loss are autografts, allografts, and bone cements. Unfortunately, autografts are limited in supply and require an invasive second surgery that can lead to donor site morbidity. Allografts are more abundant and do not require a harvesting surgery, but have there is a potential for disease transfer and decrease in mechanical strength leading to failure rates of 30-60% over a period of 10 years in vivo. Given these disadvantages, tissue engineering (TE) has been heavily explored as a promising alternative treatment. Most TE options for bone replacement seek to replace only the trabecular bone leading to low mechanical properties or lack the ability to promote early vascularization in vivo. To overcome these limitations, we have developed a novel osteoinductive pre-vascularized three-dimensional scaffold composed of electrospun synthetic and collagen-based materials with enhanced mechanics. We hypothesize the joining of a porous trabecular scaffold with the addition of hydroxyapatite (HAp), pre-vascularized cortical bone scaffold and HAp columns will promote the differentiation of human mesenchymal stem cells (hMSCs) along the osteoblastic and angiogenic lineage for improved mechanics and graft viability in vivo. Material characterization of the scaffold confirmed pore ranges necessary for neovascularization and osteoblast infiltration and mechanical properties comparable to native bone. The porous trabecular scaffold with HAp promoted osteogenic differentiation of hMSCs in vitro. The decellularized cortical scaffolds had a maintained collageneous pre-vascularized matrix, which promoted hMSCs to secrete vascular endothelial growth factor (VEGF), an early angiogenesis marker. Additionally, the hMSCs seeded on the pre-vascularized matrix developed morphology indicative of endothelial lumen development in 2D. Recent subcutaneous murine in vivo studies confirmed significant cellular infiltration and graft biocompatibility. This technology is transformative because it will be the first synthetic bone graft to contain both trabecular and cortical bone structures and be designed for vascularized bone growth and load-bearing applications.

ETD_7307

Ph.D.

Includes bibliographical references

by Brittany Louise Taylor

doi:10.7282/T31838PK

ETD doctoral

The author owns the copyright to this work.