Engineering Vascularized Bone Tissues By Microfabrication And Scaffolding

通过微加工和脚手架工程血管化骨组织

基本信息

批准号：
8434749
负责人：
YUNZHI YANG
金额：
$ 46.5万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8434749
关键词：
Biocompatible Materials Biological Biomimetics Blood Vessels Bone Regeneration Bone Tissue Bone Transplantation Calculi Cells Cephalic Chemicals Chemistry Clinical Collagen Congenital Abnormality Defect Effectiveness Engineering Ensure Environment Excision Extracellular Matrix Face Failure Fracture Fracture Healing Goals Human Hydrogels Implant In Vitro Mechanics Metabolic Microfabrication Molecular Biology Nutrient Operative Surgical Procedures Osteoblasts Outcome Oxygen Patients Procedures Property Rattus Structure Testing Tissue Engineering Tissues United States Vascular Endothelial Growth Factors Waste Products allogenic bone transplantation base bone bone cell bone engineering bone morphogenetic protein 2 calcium phosphate craniofacial craniofacial repair design design and construction functional restoration in vivo mineralization prototype repaired scaffold seal self assembly skeletal substantia spongiosa success

项目摘要

DESCRIPTION (provided by applicant): Engineering vascularized bone tissues by microfabrication and scaffolding Repair of craniofacial and other large bone defects remains a significant clinical problem. Often bone grafts are required for reconstructive skeletal procedures to aid fracture healing, bone fusion, implant integration and repair of skeletal defects, but the use of allograft bone is limited by a high failure rate. Tissue engineered constructs are promising substitutes. The major challenge of bone tissue engineering is the formation of a complete vascular network capable of delivering oxygen and nutrients and removing waste products that limits the maximum effective size of tissue engineered constructs. Most tissue engineering approaches rely on the self-assembly of cells to recreate functional vascularity on biodegradable scaffolds, but it rarely occurs. We therefore propose to construct bone tissues having a vascular network by (1) microfabricating and optimizing a vascular network with biomimetic complexity; (2) optimizing a synthetic bony environment to support the function of the microfabricated vascular networks; and (3) validating enhanced functionality of the developed vascularized bone tissue constructs in vivo. The success of this project will significantly advance the paradigm of vascular networks in engineered tissues by the creation of a vascularized bone construct prototype, with a long term goal of a new treatment in large bone defect repair in humans.

描述（由申请人提供）：通过微加工和支架工程化血管化骨组织颅面和其他大骨缺损的修复仍然是一个重要的临床问题。重建骨骼手术通常需要骨移植来帮助骨折愈合、骨融合、植入物整合和修复骨骼缺陷，但同种异体移植骨的使用因高失败率而受到限制。组织工程构建体是有前途的替代品。骨组织工程的主要挑战是形成完整的血管网络，能够输送氧气和营养物质并清除限制组织工程结构最大有效尺寸的废物。大多数组织工程方法依靠细胞的自组装在可生物降解的支架上重建功能性血管，但这种情况很少发生。因此，我们建议通过以下方式构建具有血管网络的骨组织：（1）微加工和优化具有仿生复杂性的血管网络；（2）优化合成骨环境以支持微制造血管网络的功能； (3)在体内验证所开发的血管化骨组织结构的增强功能。该项目的成功将通过创建血管化骨结构原型，显着推进工程组织中血管网络的范例，其长期目标是为人类大骨缺损修复提供新的治疗方法。