2024 AIChE Annual Meeting
(413a) Development of a Tissue Engineered Periosteum through Biomimetic Biomaterials Design
Author
Benoit, D. - Presenter, University of Rochester
Bone graft procedures cost over $2.5 billion in healthcare expenditures in the US annually, with decellularized cadaveric bone grafts (allografts) used in approximately one-third of these cases. Although allografts remain the gold standard for treating critical-size bone defects, approximately 60% fail within ten years post-implantation. Allograft failure is directly linked to the absence of periosteum, a highly vascularized and innervated tissue surrounding bone that promotes bone healing and host tissue recruitment through periosteal paracrine signaling. Considering its importance in bone healing, our focus has been on the design of hydrogel-based tissue engineered periosteum (TEP) to mimic periosteum-mediated autograft healing when allografts are used. We have developed a tissue-engineered periosteum (TEP) to improve allograft healing based on cells transplanted within poly(ethylene glycol) hydrogels. We have shown that cell persistence, cell type, and TEP hydrogel degradation mechanism are critical design criteria. Ultimately, we achieve autograft-like healing in vivo when TEP comprises mouse mesenchymal stem cells and osteoprogenitor cells encapsulated within cell-degradable hydrogels designed to degrade by 2 weeks post-implantation completely. Furthermore, the TEP cells emulate native periosteum paracrine factor production to coordinate host tissue infiltration and remodeling. Since periosteum-mediated healing occurs primarily via paracrine factors, we have subsequently leveraged RNA sequencing to identify the temporal expression of critical periosteal paracrine cues. The TEP was then designed to act as a cell and growth factor-free drug delivery depot for temporally controlled release of peptide-based paracrine mimetics and tested to improve allograft healing. Data suggests that the cell- and growth-factor-free approach improves allograft healing similar to the cellular TEP and is anticipated to reduce graft failure rates, shorten post-operation recovery, and decrease associated treatment costs.