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Endothelial cell specification at the osteogenic and angiogenic interface in cranial bone tissue engineering

颅骨组织工程中成骨和血管生成界面的内皮细胞规范

基本信息

批准号：
10618247
负责人：
XINPING ZHANG
金额：
$ 53.11万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-03 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10618247
关键词：
Address Affect Aging Allografting Arteries Autologous Transplantation BMX gene Binding Biological Markers Blood Vessels Blood capillaries Bone Regeneration Bone Tissue Cardiovascular system Cells Cephalic Clinical Coupling Defect Development Embryonic Development Endothelial Cells Endothelium Engineering Excision Genetic Goals Hypoxia Hypoxia Inducible Factor Hypoxia Pathway Image Imaging technology Implant Infection Knowledge Label Laser Scanning Microscopy Mediating Metabolic Metaphysis Modeling Molecular Profiling Morphology NADH Natural regeneration Nature Nicotinamide adenine dinucleotide Orthopedic Procedures Osteoblasts Osteogenesis Oxidation-Reduction Oxygen PECAM1 gene Pathway interactions Perfusion Play Population Regulation Resolution Role Series Site Specific qualifier value Tamoxifen Time Tissue Engineering Tissues Trauma Vascularization Veins Venous angiogenesis blood vessel development bone bone loss bone reconstruction bone repair craniomaxillofacial fluorescence lifetime imaging gain of function genetic approach genetic manipulation hypoxia inducible factor 1 imaging approach improved inducible Cre insight intravital imaging long bone loss of function migration mouse model multi-photon nanofiber novel osteogenic overexpression postnatal reconstruction regenerative repair model repaired response scaffold success tissue oxygenation tissue repair transcriptome sequencing tumor two-photon vascular bed vascular tissue engineering

项目摘要

Abstract Repair and reconstruction of bone loss due to tumor resection, trauma and infection remains a significant clinical challenge. Worldwide, autografts or allografts are used in approximately 3 million orthopaedic procedures annually, of which 6% are craniomaxillofacial in nature. Bone tissue engineering has been hailed as the ultimate solution for replacing bone autograft in repair of bone defects. However, the long-term success of bone tissue engineering is impeded by inadequate vascularization of the engineered construct. The current lack of progress in vascularization of tissue engineered scaffold is attributed to our incomplete understanding of angiogenesis and vascular beds in bone repair and regeneration. A functional blood vessel network consists of arteries, veins and a capillary interface that connects arterial and venous microvessels for proper vascular perfusion. While the specification of arterial and venous endothelium has been well studied during early embryonic development, the postnatal regulation of arterial and venous expansion and specification at capillary level during repair and regeneration is poorly understood. A series of recent studies have suggested that hypoxia affects the endothelial cell (EC) specification at the osteogenic and angiogenic interface in development and aging. Genetic manipulation of the hypoxia inducible factor 1 (HIF-1) pathway markedly affects the formation of specific subsets of capillary vessels, termed Type H (CD31highEmcnhigh) vessels that couple to OSX+ osteoblasts at the long bone metaphysis. To gain a better understanding of the critical role of hypoxia at the osteogenic and angiogenic interface in repair and regeneration, we established a series of novel imaging approaches that permit high resolution, quantitative, and functional analyses of capillary vessels that couple to Col (I) 2.3 GFP+ osteoblasts at a cranial bone defect site. Utilizing these novel imaging approaches in a layer-by-layer enabled, nanofiber-mediated cranial defect repair model, we demonstrate that osteogenesis- dependent angiogenesis consists of morphologically and functionally distinct CD31+Emcn+ and CD31+Emcn- vessels. Examination of blood vessel type distribution and bone regeneration demonstrates differential angiogenic responses and contrasting distributions of CD31+Emcn+ and CD31+Emcn- vessels associated with Col I (2.3) GFP+ osteoblasts, new bone and non-bone forming tissue, suggesting that EC specification at the capillary level is a key component of osteogenesis-dependent angiogenesis in bone repair and regeneration. Based on these findings, we propose to examine the effects of hypoxia on EC specification and the impact of dysregulation of EC specification on bone formation during cranial defect repair and regeneration. Three complementary Aims will combine imaging, genetic and engineering approaches to defining the osteogenesis- dependent EC specification and the role of hypoxia in repair and regeneration. The success of our study will provide novel insights into mechanisms of osteogenesis and angiogenesis in repair, potentially offering novel translational targets for bone regeneration.

摘要

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Periosteum Mimetic Coating on Structural Bone Allografts via Electrospray Deposition Enhances Repair and Reconstruction of Segmental Defects.

DOI：
10.1021/acsbiomaterials.0c00421
发表时间：
2020-11-09
期刊：
ACS biomaterials science & engineering
影响因子：
5.8
作者：
Zhuang Z;John JV;Liao H;Luo J;Rubery P;Mesfin A;Boda SK;Xie J;Zhang X
通讯作者：
Zhang X

Doctors vs. Nurses: Understanding the Great Divide in Vaccine Hesitancy among Healthcare Workers.

DOI：
10.1109/bigdata55660.2022.10020853
发表时间：
2022-12-01
期刊：
Proceedings : ... IEEE International Conference on Big Data. IEEE International Conference on Big Data
影响因子：
0
作者：
Ahamed, Sajid Hussain Rafi;Shakil, Shahid;Luo, Jiebo
通讯作者：
Luo, Jiebo

Electrospun core-shell nanofibers with encapsulated enamel matrix derivative for guided periodontal tissue regeneration.