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Gelatin scaffold with multifunctional curcumin-loaded lipid-PLGA hybrid microparticles for regenerating corneal endothelium
Biomaterials Advances ( IF 7.9 ) Pub Date : 2020-11-26 , DOI: 10.1016/j.msec.2020.111753
Pei-Chen Li , Szu-Ching Chen , Yi-Jen Hsueh , Yang-Chun Shen , Meng-Yu Tsai , Li-Wen Hsu , Chih-Kuang Yeh , Hung-Chi Chen , Chieh-Cheng Huang

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.



中文翻译:

具有多功能姜黄素负载脂质-PLGA杂化微粒的明胶支架可再生角膜内皮

角膜移植是目前治疗角膜盲的唯一方法。利用在支持性生物材料上生长的角膜内皮细胞(CEC)的基于细胞的策略,有望成为治疗角膜内皮功能障碍的替代疗法。但是,大多数生物材料仅由于其强大的机械性能而使用,从而为CEC单层移植提供了被动的物理支持。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,该系统不仅可以支持CEC的功能和移植,还可以通过姜黄素的持续释放来防止植入后并发症,从而提高长期应用的成功性。 CEC植入。负载姜黄素脂质-聚(乳酸-使用水包油单乳液法制备的β-乙醇酸(PLGA; Cur @ MPs)杂化微粒(MPs)嵌入基于明胶的支架中。评价了所开发的支架的抗炎,抗氧化和抗血管生成的潜力及其在支持CEC单层形成中的能力。野狗@国会议员能够促进CEC增殖,保护免受氧化应激诱导的细胞死亡的CEC通过调节Nrf2 / HO-1信号轴,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掺入薄明胶膜中,制成的支架能够支持CEC的生长和组织成具有紧密连接的多边形形态。这些实验结果证明了装载Cur @ MPs的明胶支架潜在地积极支持移植后CEC单层细胞的存活和功能。

更新日期:2020-11-26
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