Vascularization in bone tissue engineering constructs

摘要 节段性大段骨缺损的治疗仍是临床上一个重要的问题。预处理 血管化的大骨移植物能够与宿主血管床快速融合， 与天然骨组织的结合将显著地推进当前可用的治疗。 解决这些问题有望克服组织的绊脚石之一 设计和革新大面积骨缺损的治疗方法。在这个项目中，我们建议 设计一种新的预血管化骨移植替代物来修复大的骨缺损。小说 骨移植物由通道化的、可生物降解的磷酸钙-聚合物复合物组成 支架包含载有细胞的水凝胶（作为骨替代物）和柔性的，可缝合的， 抗血栓形成的、可渗透的基于聚合物的组织工程血管移植物（TEVG，如血液 船舶代理）。TEVG将以空间受控的方式并入支架中。 时尚.我们的假设是，TEVG将促进和促进微血管化， 该支架在允许外科吻合术的同时， 工程化骨移植物和宿主组织来修复大的骨缺损。为了验证我们的假设， 团队由生物材料、骨组织工程、新生血管、微生物学和生物医学领域的专家组成， 外科和矫形外科，提出了以下目标：!目标1是开发一种TEVG， 促进宿主血管整合。目标2是设计和开发一个即时集成的，预 血管化骨移植替代物。目的3是确定血管化骨的效率 组织构建原型，以增强与宿主骨组织的整合，加速骨 再生和恢复功能。这个项目的完成将使 血管化合成骨移植物设计，并为改善临床治疗铺平道路， 大段骨缺损。 !

Abstract Treatment of segmental large bone defects remains a significant clinical problem. Pre- vascularized large bone grafts capable of rapidly anastomosing with host vessel bed and integrating with native bone tissue would significantly advance currently available treatments. Addressing these issues is expected to overcome one of the stumbling blocks of tissue engineering and revolutionize the treatment of large bone defects. In this project, we propose to engineer a novel pre-vascularized bone graft substitute to repair large bone defects. The novel bone graft is comprised of a channeled, biodegradable calcium phosphate-polymer composite scaffold containing a cell-laden hydrogel (as a bone surrogate) and a flexible, suturable, antithrombotic, permeable polymer-based tissue engineered vessel graft (TEVG, as a blood vessel surrogate). The TEVG will be incorporated into the scaffold in a spatially controlled fashion. Our hypothesis is that the TEVG will facilitate and promote microvascularization across the scaffold, while allowing for surgical anastomosis to enable instant integration between the engineered bone graft and host tissue to repair large bone defects. To test our hypothesis, our team comprised of experts in biomaterials, bone tissue engineering, neovascularization, micro- surgery and orthopedic surgery, proposes the following aims:!Aim 1 is to develop a TEVG that facilitates host vascular integration. Aim 2 is to design and develop an instantly integrated, pre- vascularized bone graft substitute. Aim 3 is to determine the efficiency of a vascularized bone tissue construct prototype to enhance integration with host bone tissue, accelerate bone regeneration and restore functionality. The accomplishment of this project will revolutionize vascularized synthetic bone graft design, and pave the way for improved clinical treatments for large segmental bone defects. !