Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan; Department of Biomedical Engineering and Environmental Science, National Tsing Hua University, Hsinchu, Taiwan.
Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
Mater Sci Eng C Mater Biol Appl. 2021 Jan;120:111753. doi: 10.1016/j.msec.2020.111753. Epub 2020 Nov 26.
Corneal transplantation is currently the only approach to cure corneal blindness. Cell-based strategies that employ corneal endothelial cells (CECs) grown on supporting biomaterials hold great promise as possible alternative therapies for treating corneal endothelial dysfunction. Nevertheless, most biomaterials are used merely because of their robust mechanical properties, providing passive physical support for the transplantation of CEC monolayers. Based on the versatility of curcumin in ophthalmic applications, this study aims to develop a multifunctional scaffold system that can not only support the function and transplantation of CECs but also prevents post-engraftment complications by sustained curcumin release, thus enhancing the long-term success of CEC engraftment. Curcumin-loaded lipid-poly(lactic-co-glycolic acid) (PLGA; Cur@MPs) hybrid microparticles (MPs) fabricated using an oil-in-water single emulsion method are embedded into gelatin-based scaffolds. The anti-inflammatory, antioxidative, and anti-angiogenic potentials of the developed scaffolds and their capacity in supporting CEC monolayer formation are evaluated. The Cur@MPs are capable of promoting CEC proliferation, protecting CECs from oxidative stress-induced cell death via modulating Nrf2/HO-1 signaling axis, suppressing the secretion of pro-inflammatory cytokines by macrophages, and inhibiting the migration and angiogenesis of vascular endothelial cells. By incorporating the Cur@MPs into a thin gelatin membrane, the fabricated scaffold is able to support the growth and organization of CECs into a polygonal morphology with tight junctions. These experimental results demonstrate the potential of the Cur@MPs-loaded gelatin scaffold for actively supporting the survival and function of CEC monolayers after transplantation.
角膜移植术是目前治疗角膜盲的唯一方法。以角膜内皮细胞（CECs）为基础的策略，在生物相容性材料上培养，为治疗角膜内皮功能障碍提供了很有前途的替代疗法。然而，大多数生物材料仅因其具有稳健的机械性能而被使用，为 CEC 单层的移植提供被动的物理支持。基于姜黄素在眼科应用中的多功能性，本研究旨在开发一种多功能支架系统，不仅可以支持 CEC 的功能和移植，还可以通过持续释放姜黄素来预防植入后的并发症，从而提高 CEC 植入的长期成功率。采用油包水单乳液法制备的载姜黄素脂质-聚（乳酸-共-乙醇酸）（PLGA；Cur@MPs）复合微球（MPs）被嵌入到明胶基支架中。评估了所开发支架的抗炎、抗氧化和抗血管生成潜力及其支持 CEC 单层形成的能力。Cur@MPs 能够促进 CEC 增殖，通过调节 Nrf2/HO-1 信号通路保护 CEC 免受氧化应激诱导的细胞死亡，抑制巨噬细胞分泌促炎细胞因子，并抑制血管内皮细胞的迁移和血管生成。通过将 Cur@MPs 掺入薄的明胶膜中，所制备的支架能够支持 CEC 的生长和组织，形成具有紧密连接的多边形形态。这些实验结果表明，载 Cur@MPs 的明胶支架具有主动支持 CEC 单层移植后存活和功能的潜力。
