BME PhD Proposal Seminar: Michael Hoffman

Poly(ethylene glycol) Hydrogels as a Tissue Engineered Periosteum Mimetic for Enhanced Allograft Healing and Integration

Co-Supervised by Professor Danielle Benoit

Abstract

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). Growing evidence suggests that periosteum-mediated autograft healing is due to PC paracrine factor release as PCs persist at autografts for only ~3 weeks during healing and do not contribute to new tissue formation. Furthermore, specific cell-matrix integrin interactions have been shown critical for vascularization, a major hurdle in allograft revitalization. Currently a critical knowledge gap exists in identifying the critical cues mediating healing by the periosteum. This limitation prevents recapitulation of these cues for allograft healing, precluding evolution of superior allograft revitalization strategies. Our long-term goal is to revitalize allografts using tissue engineering strategies focused on recapitulating the critical functions of the native periosteum. Our objective is to develop poly(ethylene glycol) (PEG) based periosteum mimetics to:

• Control MSC transplantation, localization, and persistence
• Isolate critical paracrine factors necessary for healing
• To modulate cell-material interactions to promote complete allograft healing and integration.

We hypothesize that hydrogels designed to control MSC persistence and promote MSC-mediated paracrine factor release will enhance allograft healing and integration.