Molecular control of blood vessel types at the regenerative interface for engineering of osteogenic and angiogenic periosteum mimetic

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Abstract Autograft is considered the gold standard for large bone defect repair and reconstruction. The superior healing potential of autografts is attributed to the robust osteogenic and angiogenic activities of periosteum– a highly vascularized thin tissue membrane covering the outer surface of bone. To recapitulate the superior healing potential of periosteum, a series of tissue engineering strategies have been developed, aiming to construct a biomimetic tissue-engineered periosteum (TEP) for enhanced bone defect repair and reconstruction. The success of these strategies hinges on a thorough understanding of the osteogenic and angiogenic role of periosteum and a better insight into the intricate relationship between bone and vessel forming cells at the regenerative interface of periosteum-mediated repair. Supported by NIH funding, we have made a series of progresses in construction of a biomimetic functional periosteum and in understanding of the functional vascular bed at the site of periosteal repair utilizing transgenic animals that label subtypes of endothelial cells. Building on these progresses, the proposed work will focus on understanding the molecular control of periosteum-mediated bone-specialized vessel formation, with further efforts devoted to building a technological platform for controlled delivery of angiogenic and osteogenic factors for reconstruction of a pro- angiogenic and pro-osteogenic periosteum mimetic for augmented bone allograft repair. The completion of the proposed study will provide new insights into the molecular control of bone-specialized blood vessel formation during periosteum-mediated repair, further offering engineering-based strategies targeting osteogenic and angiogenic interface for augmented defect repair at a compromised periosteal site.