Centro de Investigación e Innovación Biomédica (CIIB), Universidad de los Andes, Santiago, Chile.
Cells for Cells, Santiago, Chile.
Biomed Mater. 2023 May 24;18(4). doi: 10.1088/1748-605X/acd499.
Although there have been many advances in injectable hydrogels as scaffolds for tissue engineering or as payload-containing vehicles, the lack of adequate microporosity for the desired cell behavior, tissue integration, and successful tissue generation remains an important drawback. Herein, we describe an effective porous injectable system that allowsformation of pores through conventional syringe injection at room temperature. This system is based on the differential melting profiles of photocrosslinkable salmon gelatin and physically crosslinked porogens of porcine gelatin (PG), in which PG porogens are solid beads, while salmon methacrylamide gelatin remains liquid during the injection procedure. After injection and photocrosslinking, the porogens were degraded in response to the physiological temperature, enabling the generation of a homogeneous porous structure within the hydrogel. The resultant porogen-containing formulations exhibited controlled gelation kinetics within a broad temperature window (18.5 ± 0.5-28.8 ± 0.8 °C), low viscosity (133 ± 1.4-188 ± 16 cP), low force requirements for injectability (17 ± 0.3-39 ± 1 N), robust mechanical properties after photo-crosslinking (100.9 ± 3.4-332 ± 13.2 kPa), and favorable cytocompatibility (>70% cell viability). Remarkably,subcutaneous injection demonstrated the suitability of the system with appropriate viscosity and swift crosslinking to generate porous hydrogels. The resulting injected porous constructs showed favorable biocompatibility and facilitated cell infiltration for desirable potential tissue remodeling. Finally, the porogen-containing formulations exhibited favorable handling, easy deposition, and good shape fidelity when used as bioinks in 3D bioprinting technology. This injectable porous system serves as a platform for various biomedical applications, thereby inspiring future advances in cell therapy and tissue engineering.
尽管在组织工程中作为支架或作为载药载体的可注射水凝胶已经取得了许多进展，但缺乏足够的微孔以实现所需的细胞行为、组织整合和成功的组织生成仍然是一个重要的缺点。在这里，我们描述了一种有效的多孔可注射系统，该系统允许在室温下通过常规注射器注射形成孔。该系统基于光交联鲑鱼明胶和物理交联猪明胶（PG）致孔剂的差异熔融曲线，其中 PG 致孔剂为固体珠粒，而在注射过程中鲑鱼甲基丙烯酰胺明胶保持液体状态。注射和光交联后，致孔剂响应生理温度降解，在水凝胶内产生均匀的多孔结构。所得的含致孔剂的制剂在较宽的温度范围内（18.5±0.5-28.8±0.8°C）表现出可控的凝胶动力学、低粘度（133±1.4-188±16cP）、可注射性的低力要求（17±0.3-39±1N）、光交联后的稳健机械性能（100.9±3.4-332±13.2kPa）和良好的细胞相容性（>70%细胞活力）。值得注意的是，皮下注射证明了该系统具有适当的粘度和快速交联的适用性，可生成多孔水凝胶。所得的注射多孔结构表现出良好的生物相容性，并促进了细胞渗透，有利于理想的潜在组织重塑。最后，含致孔剂的制剂在 3D 生物打印技术中用作生物墨水时具有良好的处理性能、易于沉积和良好的形状保真度。这种可注射多孔系统可作为各种生物医学应用的平台，从而为细胞治疗和组织工程的未来发展提供了启示。
