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

• 批准号: 8635210
• 负责人: YUNZHI YANG
• 金额: $ 48.43万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8635210
• 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

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）：通过微加工和支架构建血管化骨组织修复颅面和其他大骨缺损仍然是一个重要的临床问题。通常，骨移植物需要用于重建骨骼手术，以帮助骨折愈合、骨融合、植入物整合和骨骼缺损的修复，但是同种异体骨的使用受到高失败率的限制。组织工程构建物是有前途的替代物。骨组织工程的主要挑战是形成一个完整的血管网络，能够输送氧气和营养物质，并清除废物，限制了组织工程结构的最大有效尺寸。大多数组织工程方法依赖于细胞的自组装来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，我们提出通过以下方式构建具有血管网络的骨组织：（1）微制造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的血管网络的功能;以及（3）在体内验证所开发的血管化骨组织构建体的增强功能。该项目的成功将通过创建血管化骨结构原型来显著推进工程组织中血管网络的范例，其长期目标是人类大骨缺损修复的新治疗。