Dept. of Biosciences & Bioengineering, IIT Bombay, India.
Dept of Pharmacology, Delhi Pharmaceutical Sciences and Research University, New Delhi, India.
Int J Biol Macromol. 2024 Jan;254(Pt 2):127735. doi: 10.1016/j.ijbiomac.2023.127735. Epub 2023 Nov 2.
Gelatin-based hydrogels have been widely used for wound healing applications. However, increase in ligand density and reduction in pore size with increasing gelatin concentration may delay wound healing by limiting cell infiltration. In this study, we address this shortcoming by combining gelatin with gellan-which is super hydrophilic and non-adhesive to cells. We show that UV crosslinked hybrid gels composed of methacrylated gelatin (GelMA) and methacrylated gellan gum (mGG), possess considerably larger pores and improved mechanical properties compared to GelMA gels. Reduced spreading and reduced formation of focal adhesions on hybrid gels combined with lower contractility and faster detachment upon trypsin-induced de-adhesion suggests that hybrid gels are less adhesive than GelMA gels. Gradual release of fibroblast growth factor (FGF) and silver nanoparticles (AgNPs) incorporated in hybrid gels not only boosts cell migration, but also confers anti-bacterial activity against gram-positive and gram-negative bacteria at concentrations nontoxic to cells. Full thickness wound healing in Wistar rats revealed increased granulation tissue formation in hybrid gels, fastest epithelialization and highest collagen deposition in rats treated with FGF entrapped hybrid gels. Together, our results demonstrate how adhesive tuning and incorporation of bioactive factors can be synergistically combined for achieving complete wound healing.
基于明胶的水凝胶已被广泛用于伤口愈合应用。然而，随着明胶浓度的增加，配体密度的增加和孔径的减小可能会通过限制细胞浸润来延迟伤口愈合。在这项研究中，我们通过将明胶与具有超亲水性且对细胞无粘附性的结冷胶结合来解决这一缺点。我们表明，与 GelMA 凝胶相比，由甲基丙烯酰化明胶（GelMA）和甲基丙烯酰化结冷胶（mGG）组成的 UV 交联杂化凝胶具有更大的孔和改善的机械性能。杂化凝胶上细胞铺展减少和焦点粘连形成减少，结合较低的收缩性和胰蛋白酶诱导去粘连时更快的分离，表明杂化凝胶比 GelMA 凝胶的粘附性更低。掺入杂化凝胶中的成纤维细胞生长因子（FGF）和银纳米粒子（AgNP）的逐渐释放不仅促进了细胞迁移，而且在对细胞无毒的浓度下对革兰氏阳性和革兰氏阴性菌具有抗菌活性。在 Wistar 大鼠的全层伤口愈合中，发现杂化凝胶中肉芽组织形成增加，用包封 FGF 的杂化凝胶治疗的大鼠上皮化最快，胶原蛋白沉积最高。总之，我们的结果表明，如何通过协同组合调节粘附性和掺入生物活性因子来实现完全伤口愈合。
