Tissue Engineered Periosteum Approaches to Heal Bone Allograft Transplants

Figure 1: Tissue engineered periosteum (TEP) for improved bone allograft healing. Schematic depicting bone allograft modified with TEP in a murine femoral defect model. TEP hydrogel comprises 20kDa 8-arm poly(ethylene glycol) (PEG)- norbornene and crosslinked with a di-thiol crosslinker via thiol:ene chemistry. Hydrogels can be modified with tethered adhesive peptide epitopes and encapsulated cells.

Project Collaborators: Dr. Hani Awad, Dr. Regine Choe, Dr. Wakenda Tyler

Although most orthopaedic fractures heal, the clinical management of critical (>3mm) segmental defects continues to present major challenges for both amputation and limb salvage approaches. The gold standard for treatment of these defects is allografts, bone grafts from cadaveric donors. While most fractures and autografts fully heal, the healing capacity of allografts is severely limited, as the periosteum plays an essential role in the healing process of both fractures and autografts. Periosteal stem cells have been shown to be necessary for the induction of robust endochondral and intramembraneous bone formation, essential for effective healing, and neovascularization of autografts. However, allografts are processed such that there are no viable stem cells or periosteum remaining. Therefore, by providing a pseudo-periosteum to revitalize allografts, a similar robust healing response may be induced.

We aim to exploit hydrogel cell/drug delivery vehicles as a tissue-engineered periosteum, evaluating different delivery regimes and hydrogel biochemical properties to promote stem cell proliferation and differentiation in vitro and in vivo within a murine segmental defect model. Our global hypothesis is that a tissue-engineered periosteum will promote allograft integration and healing thus reducing allograft failure rates.