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

再生界面血管类型的分子控制，用于成骨和血管生成骨膜模拟物的工程

• 批准号: 10750087
• 负责人: XINPING ZHANG
• 金额: $ 55.89万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-02 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10750087
• 关键词: Allografting; Autologous Transplantation; Biology; Biomimetics; Blood Vessels; Bone Growth; Bone Marrow; Bone Resorption; Bone Surface; Cells; Chondrocytes; Coupling; Data; Defect; Deposition; Dose; Endothelial Cells; Engineering; Engraftment; Funding; Genes; Goals; Growth Factor; Homeostasis; Human; Immunofluorescence Immunologic; In Vitro; Knowledge; Label; Mediating; Modeling; Molecular; Molecular Profiling; Mus; Osteoblasts; Osteogenesis; PTGS2 gene; Pattern; Peptides; Periosteum; Polymers; Property; Role; Series; Site; Stromal Cells; Surface; Techniques; Technology; Thinness; Tissue Engineering; Tissue membrane; Tissues; Transgenic Animals; Transgenic Mice; United States National Institutes of Health; Vascularization; Work; adenoviral mediated; allogenic bone transplantation; angiogenesis; blood vessel development; bone; bone reconstruction; bone repair; clinical translation; gain of function; healing; implantation; in vivo; insight; long bone; migration; mimetics; mouse model; nanofiber; novel; osteogenic; overexpression; reconstruction; regenerative; release factor; repaired; spatiotemporal; subcutaneous; success; surface coating; technology platform; vascular bed

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.

摘要 自体骨移植被认为是大面积骨缺损修复和重建的金标准。上级 自体移植物的愈合潜力归因于骨膜的强大的成骨和血管生成活性。 覆盖在骨外表面的高度血管化的薄组织膜。概括上级 骨外膜的愈合潜力，一系列的组织工程策略已被开发，旨在 构建仿生组织工程骨膜（TEP），用于增强骨缺损修复， 重建这些策略的成功取决于对成骨细胞的彻底理解， 骨膜的血管生成作用以及更好地了解骨与血管之间的复杂关系 在骨膜介导的修复的再生界面形成细胞。在NIH基金的支持下，我们 在仿生功能性骨膜的构建和对骨组织结构的理解方面取得了一系列进展， 在骨膜修复部位的功能性血管床，利用标记 内皮细胞在这些进展的基础上，拟议的工作将集中在了解分子 控制骨膜介导的骨特异性血管形成，进一步努力致力于建立一个 用于血管生成和成骨因子的受控递送的技术平台， 用于增强骨同种异体移植修复的血管生成和促骨生成骨膜模拟物。的完成 这项研究将为骨特异性血管形成的分子控制提供新的见解 在骨膜介导的修复过程中，进一步提供了基于工程的策略， 血管生成界面，用于在受损的骨膜部位进行增强的缺损修复。