Centre for Biomaterials in Surgical Reconstruction and Regeneration, Division of Surgery & Interventional Science, University College London, 2QG, 10 Pond St, London, NW3 2PS, UK.
Institute of Materials and Manufacturing, Brunel University London, Kingston Ln, London, Uxbridge, UB8 3PH, UK.
Adv Healthc Mater. 2019 May;8(10):e1801556. doi: 10.1002/adhm.201801556. Epub 2019 Apr 4.
Despite the attention given to the development of novel responsive implants for regenerative medicine applications, the lack of integration with the surrounding tissues and the mismatch with the dynamic mechanobiological nature of native soft tissues remain in the current products. Hierarchical porous membranes based on a poly (urea-urethane) (PUU) nanohybrid have been fabricated by thermally induced phase separation (TIPS) of the polymer solution at different temperatures. Thermoresponsive stiffness softening of the membranes through phase transition from the semicrystalline phase to rubber phase and reverse self-assembly of the quasi-random nanophase structure is characterized at body temperature near the melting point of the crystalline domains of soft segments. The effects of the porous structure and stiffness softening on proliferation and differentiation of human bone-marrow mesenchymal stem cells (hBM-MSCs) are investigated. The results of immunohistochemistry, histological, ELISA, and qPCR demonstrate that hBM-MSCs maintain their lineage commitment during stiffness relaxation; chondrogenic differentiation is favored on the soft and porous scaffold, while osteogenic differentiation is more prominent on the initial stiff one. Stiffness relaxation stimulates more osteogenic activity than chondrogenesis, the latter being more influenced by the synergetic coupling effect of softness and porosity.
尽管人们关注开发用于再生医学应用的新型响应性植入物，但目前的产品仍然存在与周围组织缺乏整合以及与天然软组织的动态机械生物学性质不匹配的问题。通过在不同温度下对聚合物溶液进行热致相分离（TIPS），制备了基于聚（尿烷-脲）（PUU）纳米杂化体的分级多孔膜。通过从半结晶相到橡胶相的相变以及准随机纳米相结构的反向自组装，膜的热响应性硬度软化在接近软段结晶域熔点的体温下得到表征。研究了多孔结构和硬度软化对人骨髓间充质干细胞（hBM-MSCs）增殖和分化的影响。免疫组织化学、组织学、ELISA 和 qPCR 的结果表明，hBM-MSCs 在硬度松弛过程中保持其谱系承诺；在软而多孔的支架上有利于软骨分化，而在初始硬的支架上则更明显的成骨分化。硬度松弛刺激更多的成骨活性而不是软骨形成，后者更多地受到柔软度和多孔性协同耦合效应的影响。
