基于图案化3D打印纤维的可生物适配性肌腱支架的构建及其性能研究

The incompetent bioadaptability of scaffolds is still a challenging issue in clinical translation for tendon repair. As such, the method of design and development of an engineered core-shell tendon scaffold that comprises of micropatterned 3D printing fibers and strain-reinforced fibers, to provide both structural and mechanical bioadaptability to tendon tissue will be a breakthrough in bioscaffolding technology...The proposed core portion of scaffold in this project will be a collection of fibers forming into geometric micropatterns, which are designed based on the structure of tendon. Through turning of the fiber length and the angle between two intersected fibers, the geometric micropatterns will be able to induce cell alignment following contact guidance, and generate organized extracellular matrix identical to that found in normal tendon. This project will also apply the mechanically efficient core-shell design for the assembly of the core portion with a uniaxial-stretched fibrous shell, for the purpose to generate a reinforced scaffold adequate for tendon reconstruction. In this project, the functional assembly of core-shell tendon scaffold will be investigated, and the effects of fiber geometric pattern and chemical composition on scaffold's mechanical properties, degradation behavior, and cell alignment and tenogenesis will be studied...By this work, we try to uncover the underlying mechanisms for developing bioadaptive tendon scaffold with controllable structure and functionality. The results of this project will have insights for future design and engineering of the tendon scaffold with high bioadaptability, and might be beneficial for exploiting the 3D printing-assisted regenerative therapy in the treatment of tendon injuries.

针对肌腱修复中支架材料与组织结构和力学生物不适配的关键问题，提出通过3D打印图案化纤维与拉制增强纤维相结合来构建核-壳型支架，以期同步实现与肌腱组织的结构适配性和力学适配性，推进基于3D打印技术的肌腱再生治疗向个性化、安全化和功能化发展。为此，本项目将依据肌腱结构特征，仿生设计支架的内核纤维几何图案，并通过调控图案的纤维边长和纤维间夹角实现与肌腱组织类似的细胞线性排列和细胞外基质结构再建。在此基础上，本项目还将结合材料核-壳结构的机械高效性，进行3D打印纤维内核与拉制增强纤维外壳的组装，实现支架与肌腱的力学适配性。本项目将通过调整纤维结构和化学组分，考察支架的力学增强作用及其本质、降解行为、细胞线性与成肌腱分化机理，进而阐明支架与肌腱结构和力学适配性的关系实质。本项目的研究成果将为高生物适配性肌腱支架的设计与制备提供理论依据和科学数据，对3D打印辅助肌腱再生治疗的研究有参考价值。

针对肌腱修复中支架材料与组织结构和力学生物不适配的关键问题，提出基于近场电流体3D打印与传统加工工艺相结合，并通过研究低浓度溶液直写与单轴应变致力学增强的一般规律，来构建与肌腱结构-力学相适配的支架，推进肌腱再生治疗向个性化、安全化和功能化发展。1）实验揭示了纤维打印质量与材料组成和平台体系间的一般规律，并依据肌腱特征制备出不同微图案纤维结构，在纤维间夹角小于30°时微图案纤维具有显著的结构和力学各项异性特征,加工工艺和材料组成对纤维的降解稳定性具有协同影响。2）利用激光微加工和机械单向拉伸联合制备出微图案纤维的力学增强结构体，并揭示了薄膜结构体的表面沟槽/山脊和贯穿孔的演变规律。3）实验表明所构建的微图案纤维和力学增强体具有良好的细胞相容性，能够避免传统纤维支架中竞争性细胞响应，实现高效体外建立类似肌腱组织的细胞线性结构，并揭示了材料各项异性微结构与细胞骨架、核、以及基因表达改变之间的关联。本项目不仅实现了类肌腱线性细胞结构的再建，也阐明了微图案材料对细胞各项异性响应的规律，这些研究结果有助于建立高生物适配性医用支架的设计理论，帮助实现损伤肌腱的再生治疗。