BME PhD Thesis Defense Seminar: Michael D. Hoffman
Mesenchymal Stem Cell (MSC) Transplantation and Localization via Tissue Engineered Periosteum Coordinates Enhanced Healing of Bone Allografts
Supervised by Prof. Danielle Benoit
Allografts remain the clinical
gold standard for treatment of massive bone defects. However, allografts exhibit minimal engraftment and a 60%, 10-year post implantation failure rate due to microcrack propagation, fibrotic non-unions, delayed or absent vascularization, and minimal new bone formation. In contrast, autografts completely heal, mediated by the periosteum, a thin layer of tissue housing periosteal cells (PCs) with similar proliferative and differentiation potential as mesenchymal stem cells (MSCs). Herein, hydrolytically degradable poly(ethylene glycol) (PEG) hydrogels were utilized to transplant and localize MSCs to the surface of decellularized bone allografts, thereby creating a tissue engineered (T.E.) periosteum. Implantation of T.E. periosteum modified allografts into a murine segmental femoral defect model resulted in increased graft vascularization, callus bone formation, bridging endochondral ossification, and biomechanical strength, as compared to untreated allografts, over 16 weeks of healing. To further expedite allograft healing, and to mimic autograft growth factor production, half of the transplanted cell population within T.E. periosteum was osteogenically differentiated prior to transplantation. T.E. periosteum that included the mixed cell population expedited the rate of cartilaginous matrix resorption, callus bone formation and matrix ossification, and biomechanical graft-host integration, thereby enhancing allograft healing and integration as compared to transplantation of unmodified or osteogenic MSCs alone. Taken together, these results demonstrate that allograft healing and integration can be enhanced using cell encapsulated, hydrogel-based T.E. periosteum. Moreover, periosteum cell-associated paracrine factor production can be mimicked in the context of T.E. periosteum-modified allografts to further expedite healing and integration.