Engineering Vascularized Bone Tissues By Microfabrication And Scaffolding

描述（由申请人提供）：通过微制造和支架工程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。骨移植通常用于骨骼重建手术，以帮助骨折愈合、骨融合、植入物整合和骨骼缺损修复，但同种异体骨移植的使用受到高失败率的限制。组织工程构建物是很有前途的替代品。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，这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，我们建议通过以下方法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血管网络的功能；(3)在体内验证已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，显著推进工程组织中血管网络的范例，并具有人类大骨缺损修复的新治疗方法的长期目标。

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.