基于静电纺丝支架结构和力学特性双重调控纤维环源干细胞分化的纤维环组织再生

The current engineered bionic disc tissue is considered as a potential way for treating intervertebral disc degeneration disease, which yet still remains challenging due to the complex radial gradient of natural Annulus Fibrosus (AF) tissue in cell types, biochemical composition, microstructures and mechanical properties. Our previous study demonstrated that the differentiation of annulus fibrosus-derived stem cells (AFSCs) could be regulated by the microstructure and mechanical property of the scaffolds towards different AF cells; Decellularized Annulus Fibrous Matrix (DAFM) could mimic the biological environment of AF to maintain the characteristics of AFSCs and promote secretion of extracellular matrix. Therefore, in this project, we plan to fabricate fibrous scaffolds with similar microstructures and gradient mechanical properties as natural AF tissues, which can synergistically induce the AFSCs to differentiate into specific cell types in AF, and combine the scaffolds with DAFM to promote the secretion of extracellular matrix. Then with skew laminated method, engineered AF tissues with high biomimicry as natural AF tissues will be achieved, which will be promisingly effective in repairing the defect of AF. The success of this project will provide valuable theoretical fundamentals and practical basis for clinical application of the bionic disc tissue.

应用组织工程构建的仿生椎间盘治疗椎间盘退行性疾病具有一定的潜力，但因为天然纤维环组织在细胞类型、生化组成、微观结构和力学性能的梯度性变化而极具挑战。我们的前期研究表明，纤维支架的微观结构、力学性能能够调控纤维环源干细胞（AFSCs）向纤维环各区的细胞类型分化；脱细胞纤维环基质能够模拟纤维环组织生物环境，维持AFSCs的干细胞特性并促进细胞外基质的分泌。因此，本项目拟构建与天然纤维环组织的微观结构和力学特性梯度相似的纤维支架，协同诱导AFSCs分化成纤维环组织不同区域的细胞类型，结合脱细胞纤维环基质以促进细胞外基质的分泌，并采用斜交叠卷曲方式构建仿生纤维环组织，实现纤维环组织在细胞类型、生化组成、微观结构和力学性能的高度仿生，有效用于纤维环组织缺损的修复。本项目的成功实施将为仿生椎间盘的临床应用提供有效的理论基础和实践依据。

应用组织工程构建的仿生椎间盘治疗椎间盘退行性疾病具有一定的潜力，但因为天然纤维环组织在细胞类型、生化组成、微观结构和力学性能的梯度性变化而极具挑战。通过本项目的研究，我们制备与天然纤维环组织在微观结构、力学性能和生物环境相似的支架，其能够调控纤维环源干细胞（AFSCs ）中I 型胶原、 II 型胶原和糖聚蛋白的表达，其表达趋势与纤维环内、中、外三区的三个基因的表达相一致，同时协同诱导 AFSCs 向纤维环组织内、中、外三区的细胞类型分化，同时促进细胞外基质的分泌而提高力学性能；之后应用斜交叠卷曲技术构建与天然纤维环组织在内、中、外三区具有径向的细胞类型梯度、基质类型梯度和弹性模量梯度的仿生纤维环组织用于椎间盘的置换，其术后的MRI和相关组织学检查与正常的纤维环组织表达相一致。本项目的成功实施将为仿生椎间盘的临床应用提供有效的理论基础和实践依据。