Alginate (Alg) hydrogels, the most popular natural biomaterials, mimic extracellular matrix (ECM) microenvironment and offer potential biomedical applications. Despite their excellent properties such as biocompatibility, hydrophilicity and ionic crosslinking, the absence of an intrinsic cell adhesion domain lessens their cell-carrier applications in tissue engineering. Herein, we suggest a three-dimensional (3D) cell culture system by integrating Alg hydrogel and fibroblast-derived matrix (FDM). FDM including cell-adhesion motifs, signaling, and physico-mechanical cues is prepared by the decellularization process by avoiding unfavorable chemical reactions. This cues-integrated-biomaterials (CiB) 3D platform shows increased cell viability, proliferation, chondrogenic and osteogenic differentiation of human bone-marrow-derived mesenchymal stem cells (hMSCs) in situ. The results show that the Alg/FDM hydrogel (CiB) matrix provides an excellent microenvironment for cell adhesion and can control the differentiation of hMSCs into specific lineages. Thus, these results suggest the potential applications of the Alg/FDM hydrogel matrix as a viable 3D culture system for tissue regeneration.

藻酸盐（Alg）水凝胶是最流行的天然生物材料，可模仿细胞外基质（ECM）微环境，并提供潜在的生物医学应用。尽管它们具有出色的性能，如生物相容性，亲水性和离子交联性，但缺少固有的细胞粘附域会减少它们在组织工程中的细胞载体应用。在这里，我们建议通过整合Alg水凝胶和成纤维细胞衍生的基质（FDM）来建立三维（3D）细胞培养系统。通过去除细胞过程避免不利的化学反应，可以制备包括细胞粘附基序，信号传导和物理机械提示在内的FDM。此线索集成生物材料（CiB）3D平台显示出细胞活力，增殖，原地。结果表明，Alg / FDM水凝胶（CiB）基质为细胞粘附提供了极好的微环境，并可以控制hMSCs向特定谱系的分化。因此，这些结果表明，Alg / FDM水凝胶基质作为组织再生的可行3D培养系统的潜在应用。