CICECO, University of Aveiro, Campus Universitário de Santiago, Aveiro 3810-193, Portugal.
LAQV/REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro 3810-193, Portugal.
Mater Horiz. 2022 Feb 7;9(2):694-707. doi: 10.1039/d0mh01982h.
Hydrogels have been used in combination with cells for several biomedical and biotechnological applications. Nevertheless, the use of bulk hydrogels has exhibited severe limitations in diffusion of oxygen, nutrients, and metabolites. Here, a support for cell culture is reported where glucose is generated by the own hydrogel degradation, allowing cell survival and function while promoting tissue growth. For this purpose, laminaran (or laminarin)-based hydrogels were fabricated, immobilizing the adequate enzymes to obtain structural platforms for 3D cell culture and providing glucose feeding for metabolic activity of cells through polysaccharide degradation. We demonstrate that tumor A549 cells and human mesenchymal stem cells (hMSCs) can use the glucose resultant from the hydrogel degradation to survive and grow in non-added glucose cell culture medium. Additionally, biocompatibility and biodegradability of laminaran-based hydrogels were explored for the first time. The self-feeding hydrogels exhibited high potential in cell survival compared to native cell-laden laminaran hydrogels over two weeks of sub-cutaneous implantation. Such bioscaffolds with enzyme-empowered degradation capacity can be applied in diverse biotechnological contexts such as tissue regeneration devices, biofactories, disease models, and cell delivery systems.
水凝胶已被用于多种生物医学和生物技术应用，与细胞结合使用。然而，块状水凝胶在氧气、营养物质和代谢物的扩散方面表现出严重的局限性。在这里，我们报道了一种细胞培养的支架，其中葡萄糖是由水凝胶自身的降解产生的，允许细胞存活和功能，同时促进组织生长。为此，我们制备了以昆布多糖（或岩藻聚糖）为基础的水凝胶，固定适当的酶以获得用于 3D 细胞培养的结构平台，并通过多糖降解为细胞的代谢活动提供葡萄糖喂养。我们证明，肿瘤 A549 细胞和人间充质干细胞（hMSC）可以利用水凝胶降解产生的葡萄糖在无外加葡萄糖的细胞培养基中存活和生长。此外，我们首次探索了昆布多糖基水凝胶的生物相容性和可生物降解性。与两周皮下植入的天然细胞负载昆布多糖水凝胶相比，自喂养水凝胶在细胞存活方面表现出很高的潜力。这种具有酶驱动降解能力的生物支架可应用于多种生物技术领域，如组织再生装置、生物工厂、疾病模型和细胞输送系统。
