Department of Biomedical and Chemical Engineering, BioInspired Syracuse: Institute for Material and Living Systems, Syracuse University, Syracuse, New York, USA.
Tissue Eng Part A. 2023 Jun;29(11-12):308-321. doi: 10.1089/ten.TEA.2022.0192. Epub 2023 Mar 27.
Cell transplant therapies show potential as treatments for a large number of diseases. The encapsulation of cells within hydrogels is often used to mimic the extracellular matrix and protect cells from the body's immune response. However, cell encapsulation can be limited in terms of both scaffold size and cell viability due to poor nutrient and waste transport throughout the bulk of larger volume hydrogels. Strategies to address this issue include creating prevascularized or porous structured materials. For example, cell-laden hydrogels can be formed by porogen leaching or three-dimensional printing, but these techniques involve the use of multiple materials, long preparation times, and/or specialized equipment. Postfabrication cell seeding in porous scaffolds can result in inconsistent cell density throughout scaffold volumes and typically requires a bioreactor to ensure even cell distribution. In this study, we developed a highly cytocompatible direct cell encapsulation method during the rapid fabrication of porous hydrogels. Using sodium bicarbonate and citric acid as blowing agents, we employed photocurable polymers to produce highly porous materials within a matter of minutes. Cells were directly encapsulated within methacrylated poly(vinyl alcohol), poly(ethylene glycol), and gelatin hydrogels at viabilities as high as 93% by controlling solution variables, such as citric acid content, viscosity, pH, and curing time. Cell viability within the resulting porous constructs was high (>80%) over 14 days of analysis with multiple cell types. This work provides a simple, versatile, and tunable method for cell encapsulation within highly porous constructs that can be built upon in future work for the delivery of cell-based therapies. Impact Statement This simple method to obtain cell-laden hydrogel foams allows direct cell encapsulation within biomaterials without the need for porogens or microcarriers, while maintaining high cell viability. The successful encapsulation of multiple cell types into gas-blown hydrogels with varied chemistries shows the versatility of this method. While this work focuses on photocrosslinkable polymers, any quick gelling material could be used for foam fabrication in expansion of this work. The potential future impact of this work on the treatment of diseases and injuries that utilize cell therapies is wide-ranging.
细胞移植疗法在治疗大量疾病方面显示出潜力。将细胞封装在水凝胶中通常用于模拟细胞外基质并保护细胞免受机体免疫反应的影响。然而，由于整个较大体积水凝胶中的营养物质和废物传输较差，细胞封装在支架尺寸和细胞活力方面可能受到限制。解决此问题的策略包括创建有血管化或多孔结构的材料。例如，通过致孔剂浸出或三维打印可以形成细胞负载的水凝胶，但这些技术涉及使用多种材料、较长的准备时间和/或专用设备。在多孔支架中进行后纤维蛋白细胞接种会导致整个支架体积的细胞密度不一致，通常需要生物反应器来确保均匀的细胞分布。在这项研究中，我们在快速制造多孔水凝胶的过程中开发了一种高度细胞相容性的直接细胞封装方法。我们使用碳酸氢钠和柠檬酸作为发泡剂，使用光固化聚合物在几分钟内生产出高度多孔的材料。通过控制溶液变量（如柠檬酸含量、粘度、pH 值和固化时间），我们可以将细胞直接封装在甲基丙烯酰化聚乙烯醇、聚乙二醇和明胶水凝胶中，细胞活力高达 93%。通过对多种细胞类型进行 14 天的分析，得出的多孔结构中的细胞活力仍然很高（>80%）。这项工作提供了一种简单、通用且可调谐的方法，用于在高度多孔结构中封装细胞，这可以为未来的细胞疗法输送工作提供基础。 影响陈述 这种简单的方法可获得细胞负载水凝胶泡沫，无需使用致孔剂或微载体即可直接在生物材料中封装细胞，同时保持高细胞活力。成功地将多种细胞类型封装到具有不同化学性质的气体吹制水凝胶中，展示了该方法的多功能性。虽然这项工作侧重于光交联聚合物，但任何快速胶凝材料都可以用于扩展这项工作的泡沫制造。这项工作对利用细胞疗法治疗疾病和损伤的潜在未来影响是广泛的。
