3D打印含锰梯度空心管生物活性支架用于骨-软骨一体化修复及其机制研究

Articular cartilage repair is still a great challenge in the field of orthopedic surgery. Previous studies have found that the osteochondral conducive scaffold may be a reliable substitute for articular defect. However, by virtue of the different physiological and pathological characteristics of articular cartilage and subchondral bone, the scaffolds’ capability in promoting the reconstruction of biomimetic osteochondral three-dimensional structure with concurrent regeneration of articular cartilage and subchondral bone is still limited. This has been especially true as a technical hurdle for large-size articular osteochondral defect repair. As a multi-lineage conducive biofactor, it has been proven that Manganese ions (Mn2+) could simultaneously promote osteogenic differentiation of stem cells and the phenotypic maintenance of cartilaginous tissue. Meanwhile, compared to conventional methods, three-dimensional printing (3D-Printing) offers a new way to prepare porous scaffolds with more controllable biomimetic structures for tissue engineering. To address the relevant issues, the current study will build up a porous bioceramics scaffold with controlled-release of Mn2+ ions in promoting articular cartilage regeneration. Meanwhile, biomimetic hollow struts-gradient packed structure of proposed scaffold will be achieved by 3D-printing method in promoting subchondral bone regeneration. The insights of regeneration and regulation will be gained through the observation of the synergistic effect of Mn2+ ions and biomimetic structure where stem cell biological responses including cell adhesion, differentiation, extracellular matrix accumulation, relative gene expression, and the underlying signaling pathways occurred. The successful completion of this project will develop an integrated method for the construction of osteochondral conducive scaffold that is capable of promoting better regeneration of both articular cartilage and subchondral bone in large size articular osteochondral defect.

在软骨组织工程化修复的研究中，最突出的问题之一是如何通过精细控制骨-软骨一体化修复支架的材料组成与三维结构，以实现对支架成骨、成软骨双向诱导分化及体内关节软骨、软骨下骨一体化再生的有效调控。我们的前期研究发现含锰（Mn）生物陶瓷能够可控释放Mn等生物活性离子实现双向诱导分化，超精细三维（3D）打印的梯度化空心管堆叠的多孔结构相对于传统3D打印多孔结构具备更利于促进骨、软骨一体化再生的仿生微结构。因此，本项目拟构建3D打印含锰梯度空心管生物陶瓷支架，利用Mn双向诱导分化特性与3D打印空心管梯度化堆叠的微结构来协同促进软骨、软骨下骨的再生；并深入揭示支架的组成与结构对其理化性能、微循环流动特性、干细胞成骨/成软骨双向诱导分化及体内骨-软骨一体化修复能力的影响及其相应机制；最终将可能发展一类组成与结构可控、生物学性能优良的骨-软骨一体化修复支架，为实现稳定的大面积软骨修复提供新理论和新方法。

在软骨组织工程化修复的研究中，最突出的问题之一是如何通过精细控制骨-软骨一体化修复支架的材料组成与三维结构，以实现对支架成骨、成软骨双向诱导分化及体内关节软骨、软骨下骨一体化再生的有效调控。我们的前期研究发现含锰（Mn）生物陶瓷能够可控释放Mn等生物活性离子实现双向诱导分化，超精细三维（3D）打印的梯度化空心管堆叠的多孔结构相对于传统3D打印多孔结构具备更利于促进骨、软骨一体化再生的仿生微结构。因此，本项目拟构建3D打印含锰梯度空心管生物陶瓷支架，利用Mn双向诱导分化特性与3D打印空心管梯度化堆叠 的微结构来协同促进软骨、软骨下骨的再生；并深入揭示支架的组成与结构对其理化性能、微 循环流动特性、干细胞成骨/成软骨双向诱导分化及体内骨-软骨一体化修复能力的影响及其相应机制；最终将可能发展一类组成与结构可控、生物学性能优良的骨-软骨一体化修复支架，为实现稳定的大面积软骨修复提供新理论和新方法。