Engineering Vascularized Bone Tissues By Microfabrication And Scaffolding

描述(申请人提供)：通过微制造和支架修复颅面部和其他大型骨缺损来工程血管化骨组织仍然是一个重要的临床问题。骨重建手术通常需要骨移植，以帮助骨折愈合、骨融合、种植体整合和修复骨缺损，但同种异体骨的使用受到高失败率的限制。组织工程构建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，并清除限制组织工程构造最大有效尺寸的废物。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(1)微制造和优化具有仿生复杂性的血管网络；(2)优化合成的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结构的增强功能，来构建具有血管网络的骨组织。该项目的成功将极大地推动工程组织中血管网络的范例，创造一种血管化的骨构造原型，长期目标是在人类的大型骨缺损修复中找到一种新的治疗方法。 公共卫生相关性：修复颅面部和其他大型骨缺损仍然是一个重大的临床挑战。该项目有望通过微制造和支架技术大规模形成完整的血管网络，从而在骨组织工程领域产生新的范式。

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. PUBLIC HEALTH RELEVANCE: Repair of craniofacial and other large bone defects remains a significant clinical challenge. This project is expected to generate a new paradigm in bone tissue engineering by enabling the formation of a complete vascular network at a large scale by microfabrication and scaffolding.