力学刺激下胶原液晶复合材料对人脐带干细胞的调控机制及三元复合体系对腰椎融合作用研究

The development of bone tissue engineering experienced the beginning excitement and now encounter many challenges, such as the source of seed cells, the maintenance of the cellular activity, the extracellular matrix secretion, lamellar tissue regeneration,the specific response with the scaffolds, vascular and nerve regeneration. The different culture environment between in vivo and in vitro, and the tissue construct technology also make the present studies are limited to isolated cell culture in vitro and cell-free materials in vivo, which is far from the expectation of living tissue reconstruction. To solve this bottleneck problem, low immunogenicity, high proliferative human umbilical cord mesenchymal stem cells (hUCMSCs) is used as seed cells, the multi-level openings materials prepared under the young fund with in-situ introduction of aligned collagen fibers as the scaffolds to enhance the in vitro biological information. The mediation of the the liquid crystalline properties, mechanical stimulation and scaffolds in vitro on hUCMSCs will be studied. The ternary complex after in vitro incubation, will be used for the treatment of common diseases of the lumbar spine defects, rabbits as model animals. The allogeneic, vessel and nerve regeneration, and spinal fusion results will be disscussed. The clinical feasibility of the corporation of stem cell transplantation and tissue engineering technologies will be explored.

骨组织工程的发展经历兴奋期后遇到了很多挑战，包括种子细胞的来源、细胞活性的保持、细胞外基质分泌、板层组织再生、与支架材料的特异性响应及血管神经再生等问题，体内外环境差异和组织构建技术也使得目前研究局限于孤立的体外细胞培养和体内无细胞材料的组织修复，与期望中的活体组织重建相差甚远。为解决此瓶颈问题，本项目采用免疫原性低、增殖能力强的人脐带间充质干细胞（hUCMSCs）作为种子细胞，以青年基金制备的多级开孔材料原位引入有序胶原纤维为支架，以增强体外培养环境中的生物学信息，研究液晶性、力学刺激及支架对hUCMSCs的体外介导作用。并以兔为模型动物，将体外孵化的三元复合体系用于常见疾病腰椎缺损的治疗，考察hUCMSCs的异体通用性、血管神经再生及脊柱融合效果，探索干细胞移植和组织工程联合技术在临床上的可行性。

本项目利用多级开孔材料原位引入有序胶原纤维为支架，以增强体外培养环境中的生物学信息，研究了胶原有序性、力学刺激及支架对人脐带间充质干细胞（hUCMSCs）的体外介导作用。并以兔为模型动物，将体外孵化的三元复合体系用于常见疾病腰椎缺损的治疗，考察了hUCMSCs 的异体通用性、血管神经再生及脊柱融合效果，探索了干细胞移植和组织工程联合技术在临床上的可行性。结果表明有序性胶原凝胶有利于干细胞的增殖分化及有序排列。为了增强胶原水凝胶的力学强度和稳定性，本项目还分别引入了天然多糖透明质酸、海藻酸钠等制备复合水凝胶，并对其一系列理化性能和生物学性能进行了评价，得到了较好的效果。三元复合支架的动物实验表明干细胞和胶原水凝胶的引入能够对椎间盘组织的重建带来积极的影响，除了能引导骨组织生成，还具有促进胶原纤维生成的潜力！其再生机制和促进效果将进一步深入研究。