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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的自体移植被认为是大骨缺损修复和重建的金标准。自体移植物的愈合潜力归因于骨膜强大的成骨和血管生成活性覆盖骨外表面的高度血管化的薄组织膜以概括上级。为了发挥骨膜的愈合潜力，开发了一系列组织工程策略，旨在构建仿生组织工程骨膜（TEP）以增强骨缺损修复和这些策略的成功取决于对成骨和成骨的透彻理解。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 NIH 资助的支持下，我们在骨膜介导的修复的再生界面形成细胞。在仿生功能骨膜的构建和对骨膜的认识方面取得了一系列进展利用标记亚型的转基因动物在骨膜修复部位建立功能性血管床基于这些进展，拟议的工作将侧重于了解分子。控制骨膜介导的骨特化血管形成，进一步致力于建立用于受控输送血管生成和成骨因子以重建亲骨细胞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成骨骨膜模拟物。拟议的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，进一步提供针对成骨和修复的基于工程的策略血管生成界面，用于增强受损骨膜部位的缺损修复。