纳米中空微球联合温敏双壳层聚离子胶束再生髓核

Mesenchymal stem cells (MSCs), tissue engineering and gene therapy provide a potential solution to intervertebral disc (IVD) degeneration. Although the beneficial effects of intradiscal injection have been proven, it remains challenging to obtain tissue regeneration at the desired scale. Therefore combinatorial approaches that encompasses cell therapy, gene therapy and tailored biomaterials is a preferred option. The extracellular matrix (ECM) plays an important role in stem cell niche, a good cell carriers should mimic the advantage features of natural ECM. Here, we try to fabricate nanofibrous hollow microspheres self-assembled from star-shaped biodegradable polymers as an injectable cell carrier. The nanobibrous hollow microspheres, integrating the extracellular-matrix-mimicking architecture with a highly porous injectable form, could efficiently accommodate cells and enhance IVD regeneration. In our previous work, an efficient nonviral cationic block copolymer gene delivery system was used to deliver therapeutic plasmid DNA (pDNA), which was prepared via complexation between the mixed cationic block copolymers and plasmid DNA (pDNA). The mixed polyplex micelles (MPMs) containing heterogeneous coronas with hydrophobic and hydrophilic microdomains coexisting could be obtained upon heating from 25 to 37 oC, which showed high gene transfection efficiency towards NP cells in the in vitro and in vivo evaluation due to the synergistic effect of significantly improved colloidal and complex stability and low cytotoxicity. Therefore, based on our previous work, we focus on a combinatorial approach, which provides both biochemical and physical cues for stem cells differentiation, to retard or regenerate the degenerative discs.

干细胞、组织工程以及基因治疗技术的发展使椎间盘再生成为可能。尽管直接注射干细胞具有一定的疗效，但注射后细胞常因为缺乏细胞外基质提供的锚点而死亡，以及缺乏适当的细胞外信号引导而无法分化为髓核细胞发挥功能。因此，通过生物材料作为桥梁，整合组织工程及基因治疗各自的优势，建立综合性的治疗策略（能同时提供干细胞及其增殖分化所需的物理、化学信号）是目前亟需解决的问题。课题组将星形聚乳酸自组装制备纳米中空微球，表面具有模拟细胞外基质（主要由直径50-500纳米的纤维组成）的纳米纤维结构，理论上能有效容纳细胞并促进再生。同时，我们前期工作中合成两种嵌段聚合物与DNA络合形成温敏双壳层聚离子复合物胶束（MPMs） 可作为安全低毒高效的非病毒基因治疗载体。基于前期的工作基础，本项目将进一步围绕构建干细胞微环境探索纳米中空微球联合高分子胶束在再生椎间盘方面的设计和应用规律，为椎间盘退变治疗策略提供思路。

干细胞、组织工程以及基因治疗技术的发展使椎间盘再生成为可能。尽管直接注射干细胞具有一定的疗效，但注射后细胞常因为缺乏细胞外基质提供的锚点而死亡，以及缺乏适当的细胞外信号引导而无法分化为髓核细胞发挥功能。因此，通过生物材料作为桥梁，整合组织工程及基因治疗各自的优势，建立综合性的治疗策略（能同时提供干细胞及其增殖分化所需的物理、化学信号）是目前亟需解决的问题。课题组将星形聚乳酸自组装制备纳米中空微球，表面具有模拟细胞外基质（主要由直径50-500纳米的纤维组成）的纳米纤维结构，理论上能有效容纳细胞并促进再生。同时，我们前期工作中合成两种嵌段聚合物与DNA络合形成温敏双壳层聚离子复合物胶束（MPMs） 可作为安全低毒高效的非病毒基因治疗载体。基于前期的工作基础，本项目将进一步围绕构建干细胞微环境探索纳米中空微球联合高分子胶束在再生椎间盘方面的设计和应用规律，为椎间盘退变治疗策略提供思路。