Department of Bioengineering, Hanyang University, 222 Wangsimri-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, 222 Wangsimri-ro, Seongdong-gu, Seoul 04763, Republic of Korea.
Department of Bioengineering, Hanyang University, 222 Wangsimri-ro, Seongdong-gu, Seoul 04763, Republic of Korea.
Acta Biomater. 2022 Sep 1;149:96-110. doi: 10.1016/j.actbio.2022.06.043. Epub 2022 Jun 30.
Gelatin methacryloyl (GelMA) hydrogels have been widely used for cell encapsulation in tissue engineering due to their cell adhesiveness and biocompatibility. However, free radicals generated during gelation decrease the viability of the encapsulated cells by increasing intracellular oxidative stress, so appropriate strategies for scavenging free radicals need to be developed. To meet that need, we developed composite GelMA hydrogels incorporating nanofiber particles (EF) coated with epigallocatechin-gallate (EGCG). The GelMA composite hydrogels were successfully fabricated and had a storage modulus of about 5 kPa, which is similar to that of pristine GelMA hydrogel, and the drastic free radical scavenging activity of EGCG was highly preserved after gelation. In addition, human adipose-derived stem cells encapsulated within our composite hydrogels had better viability (about 1.5 times) and decreased intracellular oxidative stress (about 0.3 times) compared with cells within the pristine GelMA hydrogel. We obtained similar results with human dermal fibroblasts and human umbilical vein endothelial cells, indicating that our composite hydrogels are suitable for various cell types. Furthermore, we found that the ability of the encapsulated cells to spread and migrate increased by 5 times within the composite hydrogels. Collectively, our results demonstrate that incorporating EF into GelMA hydrogels is a promising way to enhance cell viability by reducing free-radical-derived cellular damage when fabricating 3D tissue ex vivo. STATEMENT OF SIGNIFICANCE: Gelatin methacryloyl (GelMA) hydrogels have been widely applied to various tissue engineering applications because of their biocompatibility and cell interactivity. However, free radicals generated during the GelMA hydrogel fabrication decrease the viability of encapsulated cells by elevating intracellular oxidative stress. Here, we demonstrate radical scavenging GelMA hydrogels incorporating epigallocatechin-gallate (EGCG)-coated nanofiber particles (EF). The composite GelMA hydrogels are successfully fabricated, maintaining their mechanical properties, and the viability of encapsulated human adipose-derived stem cells is greatly improved after the gelation, indicating that our composite GelMA hydrogel alleviates damages from free radicals. Collectively, the incorporation of EF within GelMA hydrogels may be a promising way to enhance the viability of encapsulated cells, which could be applied to 3D tissue fabrication.
明胶甲基丙烯酰（GelMA）水凝胶由于其细胞黏附性和生物相容性而被广泛用于组织工程中的细胞封装。然而，凝胶过程中产生的自由基会通过增加细胞内氧化应激来降低被包裹细胞的活力，因此需要开发适当的清除自由基的策略。为了满足这一需求，我们开发了一种复合 GelMA 水凝胶，其中包含纳米纤维颗粒（EF），表面涂有表没食子儿茶素没食子酸酯（EGCG）。成功制备了 GelMA 复合水凝胶，其储能模量约为 5kPa，与原始 GelMA 水凝胶相似，并且 EGCG 的自由基清除活性在凝胶化后得到了高度保留。此外，与原始 GelMA 水凝胶中的细胞相比，封装在我们的复合水凝胶中的人脂肪来源干细胞具有更好的活力（约 1.5 倍）和降低的细胞内氧化应激（约 0.3 倍）。我们用人真皮成纤维细胞和人脐静脉内皮细胞得到了类似的结果，表明我们的复合水凝胶适用于各种细胞类型。此外，我们发现，在复合水凝胶中，被包裹细胞的扩散和迁移能力增加了 5 倍。总的来说，我们的结果表明，将 EF 掺入 GelMA 水凝胶中是一种很有前途的方法，可以通过降低自由基衍生的细胞损伤来提高细胞活力，从而在体外制造 3D 组织。
