Background Gelatin methacryloyl (GelMA) hydrogels loaded with stem cells have proved to be an effective clinical treatment for wound healing. Advanced glycation end product (AGE), interacting with its particular receptor (AGER), gives rise to reactive oxygen species (ROS) and apoptosis. Curcumin (Cur) has excellent antioxidant activity and regulates intracellular ROS production and apoptosis. In this study, we developed a Cur-incorporated 3D-printed GelMA to insert into adipose-derived stem cells (ADSCs) and applied it to diabetic wounds. Methods GelMA hydrogels with Cur were fabricated and their in vitro effects on ADSCs were investigated. We used structural characterization, western blot, ROS and apoptosis assay to evaluate the antioxidant and anti-apoptotic activity, and assessed the wound healing effects to investigate the mechanism underlying regulation of apoptosis by Cur via the AGE/AGER/nuclear factor-κB (NF-κB) p65 pathway. Results A 10% GelMA scaffold exhibited appropriate mechanical properties and biocompatibility for ADSCs. The circular mesh structure demonstrated printability of 10% GelMA and Cur-GelMA bioinks. The incorporation of Cur into the 10% GelMA hydrogel showed an inhibitory effect on AGEs/AGER/NF-κB p65-induced ROS generation and ADSC apoptosis. Furthermore, Cur-GelMA scaffold promoted cell survival and expedited in vivo diabetic wound healing. Conclusions The incorporation of Cur improved the antioxidant activity of 3D-printed GelMA hydrogel and mitigated AGE/AGER/p65 axis-induced ROS and apoptosis in ADSCs. The effects of scaffolds on wound healing suggested that Cur/GelMA-ADSC hydrogel could be an effective biological material for accelerating wound healing.

中文翻译：

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掺入姜黄素的 3D 生物打印明胶甲基丙烯酰水凝胶可减少活性氧诱导的脂肪干细胞凋亡并提高糖尿病伤口的植入存活率。

背景 载有干细胞的明胶甲基丙烯酰 (GelMA) 水凝胶已被证明是一种有效的伤口愈合临床治疗方法。晚期糖基化终产物 (AGE) 与其特定受体 (AGER) 相互作用，产生活性氧 (ROS) 和细胞凋亡。姜黄素 (Cur) 具有优异的抗氧化活性并调节细胞内 ROS 的产生和细胞凋亡。在这项研究中，我们开发了一种结合 Cur 的 3D 打印 GelMA，可插入脂肪干细胞 (ADSC) 并将其应用于糖尿病伤口。方法制备具有Cur的GelMA水凝胶，并研究其对ADSCs的体外影响。我们使用结构表征、蛋白质印迹、活性氧和细胞凋亡测定来评估抗氧化和抗细胞凋亡活性，并评估伤口愈合效果以研究 Cur 通过 AGE/AGER/核因子-κB (NF-κB) p65 途径调节细胞凋亡的机制。结果 10% GelMA 支架对 ADSC 表现出适当的机械性能和生物相容性。圆形网状结构展示了 10% GelMA 和 Cur-GelMA 生物墨水的可印刷性。Cur 掺入 10% GelMA 水凝胶对 AGEs/AGER/NF-κB p65 诱导的 ROS 生成和 ADSC 凋亡具有抑制作用。此外，Cur-GelMA 支架可促进细胞存活并加速体内糖尿病伤口愈合。结论 Cur 的加入提高了 3D 打印 GelMA 水凝胶的抗氧化活性，并减轻了 AGE/AGER/p65 轴诱导的 ADSCs 活性氧和凋亡。