3D打印新型掺锂n-HA/PA/PCL支架复合BMSCs修复大段骨缺损的研究

Large bone defects of various causes is one of the thorny problems frequently encountered in daily clinical practice. Finding a proper bone repair material remains a tremendous challenge in the filed of orthopedics and the biomaterial. Wnt signaling plays a vital role in regulating the proliferation and osteogenic differentiation of BMSCs under certain cellular contexts. Lithium can promote osteogenesis by activating the Wnt signaling pathway. Inhibition of glycogen synthease kinase 3 (GSK3) by lithium mimics the effects of canocial Wnt signaling. Activation of Wnt signaling leads to inhibition of GSK3 mediated phosphoxylation of a downstream transcription factor β-catenin and prevents its subsequent degradation by the preoteasome complex. The synergism of stem cell biology and biomaterial technology as well as activation of related signal cascades via bioactive material promises BMSCs directed osteogenic differentiation and facilitate tissue regeneration. Moreover, the 3D printing technology based individualized biomaterial can realize the individuation of material preparation and can be used to imitate the anatomy and physiological characters of the defect area. This program aimed to use 3D printing technology to produce a new type of lithium doped n-HA/PA/PCL individualized bionic scaffold, consistent with BMSCs, implanted in the animal models of the large bone defects and study ability of scaffold to repair bone defect and reconstruct mechanics, providing new ideas and methods to the clinical treatment of large bone defects.

各种原因引起的大段骨缺损是骨科临床上经常遇到的棘手问题之一，寻找合适的骨科修复材料一直是骨科和生物材料领域面临的艰巨挑战。Wnt信号通路是调控BMSCs向成骨细胞分化的关键通路。锂盐可以促进成骨，抑制糖原合成激酶3β（GSK-3β）、阻断其对Wnt通路关键因子β-catenin磷酸化被认为是锂盐激活Wnt信号通路、促进成骨的基础。基于干细胞生物特性和生物材料协同的组织工程，以及具有生物活性的生物材料激活相关信号通路，可以调控BMSCs定向成骨分化，促进组织、器官再生。而基于3D打印技术的个体化仿生生物材料可以实现材料制备的个体化，可以最大程度模拟修复部位组织的解剖学、生理学特性。本项目通过基于三维CT数据的3D打印技术制备新型掺锂n-HA/PA/PCL个体化仿生支架，同时复合BMSCs，植入大段骨缺损的动物模型体内，研究支架修复骨缺损、重建力学的能力，为临床治疗大段骨缺损提供新思路。

各种原因引起的大段骨缺损是骨科临床上经常遇到的棘手问题之一，寻找合适的骨科修复材料一直是骨科和生物材料领域面临的艰巨挑战。Wnt信号通路是调控BMSCs向成骨细胞分化的关键通路。锂盐可以促进成骨，抑制糖原合成激酶3β（GSK-3β）、阻断其对Wnt通路关键因子β-catenin磷酸化被认为是锂盐激活Wnt信号通路、促进成骨的基础。基于干细胞生物特性和生物材料协同的组织工程，以及具有生物活性的生物材料激活相关信号通路，可以调控BMSCs定向成骨分化，促进组织、器官再生。而基于3D打印技术的个体化仿生生物材料可以实现材料制备的个体化，可以最大程度模拟修复部位组织的解剖学、生理学特性。本项目通过基于三维CT数据的3D打印技术制备新型掺锂n-HA/PLA个体化仿生支架，同时复合BMSCs，植入节段性骨缺损的动物模型体内，研究支架修复骨缺损、重建力学的能力，为临床治疗大段骨缺损提供新思路。