构建具有结构高度仿生的新型组织工程骨

Reconstruction of large segmental bone defects after extensive bone loss remains a significant clinical challenge. In view of the limited availability of autografts and allografts for such application, bone tissue engineering holds great promise for addressing the above challenge by providing implantable living tissues. Despite significant progresses in fabrication of cancellous bone with highly porous structures, very limited attempts have been made to create dense cortical bone, due to its complex and hierarchical structure, which is difficult to be recapitulated via conversional tissue engineering approach. The cortical bone consists of compactly arranged repeating units - osteons. Therefore, this project proposes a novel bottom-up assembly approach to create biomimetic cortical bone. Briefly, biomimetic osteons will be first fabricated as the basic structural and functional units (small building blocks), and then assembled together to form a large-scale bone construct, which not only recapitulates the hierarchical structure of native cortical bone, but also realizes its complex biological functions. In recognition of the essence of creation of “osteon-like” units, electrospining and 3D printing techniques will be used to fabricate a bi-layered tubular structure to mimic the micro-structure of osteon and introduce the endothelialized channel. The success of proposed research will offer a novel platform to create biomimetic bone grafts for reconstruction surgery in orthopedic application, but also serve as a fundamental yet essential blueprint to generate other complex tissues and organs.

大段骨缺损的修复是临床医学的一大难题，而用于治疗的自体和异体骨移植体的来源极其有限。骨组织工程技术的出现为解决这一难题带来了希望。尽管当前组织工程化松质骨的制备已取得了显著的进展，然而体外构建皮质骨的尝试却十分有限，这是因为天然皮质骨具有致密且复杂的多级结构，难以采用传统组织工程方法来制备。鉴于在结构上，皮质骨是由紧密排列的重复单元——骨单位所组成，本项目提出了一种新颖“从下至上组合法”来构建结构仿生型骨，即：以仿生型骨单位作为基本的结构和功能单位，然后进一步通过仿生组合来构建大块的骨组织，将有望重建皮质骨的复杂、多级结构，并实现其功能仿生。其中，骨单位的结构仿生是至关重要的一步。本项目拟结合静电纺丝和3D打印技术来制备双层管状支架，从而模拟骨单位的微结构并引入血管化通路。这种结构高度仿生型骨具有良好的临床应用前景，也可为其它复杂组织的构建起到重要的示范及指导作用。

本项目着眼于解决大段骨缺损的修复，其一直是困扰临床医学的一大难题。我们提出了一种新颖“从下至上组合法”来构建结构仿生型骨，即：以仿生型骨单位作为基本的结构和功能单位，然后进一步通过仿生组合来构建大块的骨组织，以此方法来重建天然骨的复杂、多级结构，并实现其功能仿生。首先，我们结合静电纺丝和3D打印技术制备了双层管状支架，并且精确调控了成骨细胞和血管内皮细胞的空间分布，充分模拟骨单位的微结构并引入血管化通路；再次，以这种仿生骨单位作为基本的结构单位，通过精密组装构建了大尺度的组织工程化骨移植体。这种结构高度仿生型骨移植体具有良好的临床应用前景，也可为其它复杂组织的构建起到重要的示范及指导作用。