Department of Bioengineering, School of Engineering, The University of Tokyo, Bunkyo-ku 113-8656, 7-3-1 Hongo, Japan.
Biomater Sci. 2019 Jun 25;7(7):2793-2802. doi: 10.1039/c9bm00093c.
Three-dimensional tissue organization is still an obstacle in the field of tissue engineering, which generally involves cell immobilization, proliferation, and organization. As an artificial extracellular matrix (ECM) for providing a suitable environment of cells to construct tissues, combination of cytocompatible polymer hydrogels and natural ECM produced by the immobilized cells was considered. In this research, we designed a spontaneously forming hydrogel system between two water-soluble polymers for the immobilization of cells. These polymers were poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate-co-p-vinylphenylboronic acid-co-N-succinimidyloxycarbonyl tetra(ethylene glycol)methacrylate) (PMBVS) and poly(vinyl alcohol) (PVA) to form a PMBVS/PVA hydrogel in a cell culture medium under mild conditions. Basic fibroblast growth factor (bFGF) was conjugated with PMBVS (PMBV-bFGF). To enhance the growth of the immobilized cells, mouse fibroblast L929 cells were immobilized in the PMBVS/PVA hydrogel and the PMBV-bFGF/PVA hydrogel, and their proliferation and secretion of the ECM under stimulation with bFGF was observed. The ECM infiltrated and replaced the hydrogel, resulting in the formation of a hybrid hydrogel with the ECM and laden cells.
三维组织构建仍然是组织工程领域的一个障碍,该领域通常涉及细胞固定化、增殖和组织化。作为提供细胞构建组织的合适环境的人工细胞外基质(ECM),考虑了细胞相容性聚合物水凝胶与固定化细胞产生的天然 ECM 的结合。在这项研究中,我们设计了一种在两种水溶性聚合物之间形成的自发生成水凝胶系统,用于细胞固定化。这些聚合物为聚(2-甲基丙烯酰氧乙基磷酸胆碱-co-正丁基甲基丙烯酸酯-co-p-乙烯基苯硼酸-co-N-琥珀酰亚胺基氧基羰基四(乙二醇)甲基丙烯酸酯)(PMBVS)和聚乙烯醇(PVA),在温和条件下在细胞培养基中形成 PMBVS/PVA 水凝胶。碱性成纤维细胞生长因子(bFGF)与 PMBVS (PMBV-bFGF)偶联。为了增强固定化细胞的生长,将小鼠成纤维细胞 L929 细胞固定在 PMBVS/PVA 水凝胶和 PMBV-bFGF/PVA 水凝胶中,并观察 bFGF 刺激下它们对 ECM 的增殖和分泌。ECM 渗透并取代水凝胶,导致 ECM 和负载细胞的杂交水凝胶的形成。