Demenj Marko, Žabčić Martina, Vukomanović Marija, Ilić-Tomić Tatjana, Milivojević Dušan, Tomić Simonida, Živanović Dubravka, Babić Radić Marija M
University of Belgrade, University Clinical Center of Serbia, Clinic of Dermatology and Venereology, Pasterova 2, 11000 Belgrade, Serbia.
Advanced Materials Department, Jožef Stefan Institute, Jamova Cesta 39, 1000 Ljubljana, Slovenia.
Pharmaceutics. 2025 Jan 12;17(1):89. doi: 10.3390/pharmaceutics17010089.
To develop and evaluate graphene oxide/gelatin/alginate scaffolds for advanced wound therapy capable of mimicking the native extracellular matrix (ECM) and bio-stimulating all specific phases of the wound healing process, from inflammation and proliferation to the remodeling of damaged skin tissue in three dimensions. The scaffolds were engineered as interpenetrating polymeric networks by the crosslinking reaction of gelatin in the presence of alginate and characterized by structural, morphological, mechanical, swelling properties, porosity, adhesion to the skin tissue, wettability, and in vitro simultaneous release of the active agents. Biocompatibility of the scaffolds were evaluated in vitro by MTT test on fibroblasts (MRC5 cells) and in vivo using assay. The scaffolds exhibited a highly porous interconnected morphology with adjustable porosity (93-96%) and mechanical strength (1.10-2.90 MPa), hydrophilic nature with high capacity to absorb physiological fluids, and stable adhesion to the skin tissue. The obtained results of MRC5 cell viability indicate that the scaffolds are safe for biomedical applications. No mortality was detected among the throughout the incubation period, indicating that the scaffolds are not toxic. The results of in vitro release study of allantoin, quercetin, and caffeic acid confirm the scaffolds' significant potential for simultaneous release. The graphene oxide/gelatin/alginate scaffolds are promising candidates for non-invasive, dual ECM-mimetic, and multi-target wound therapy, offering an innovative strategy to address the complexities of wound healing process.
为了开发和评估氧化石墨烯/明胶/海藻酸盐支架用于先进的伤口治疗，该支架能够模拟天然细胞外基质（ECM）并在三维空间中对伤口愈合过程的所有特定阶段进行生物刺激，从炎症和增殖到受损皮肤组织的重塑。通过在海藻酸盐存在下明胶的交联反应将支架设计成交互穿聚合物网络，并通过结构、形态、机械、膨胀性能、孔隙率、对皮肤组织的粘附性、润湿性以及活性剂的体外同步释放来表征。通过对成纤维细胞（MRC5细胞）的MTT试验在体外评估支架的生物相容性，并在体内使用试验进行评估。支架呈现出高度多孔的相互连接形态，孔隙率可调节（93-96%），机械强度为（1.10-2.90MPa），具有亲水性，能够吸收大量生理流体，并且对皮肤组织具有稳定的粘附性。MRC5细胞活力的结果表明该支架在生物医学应用中是安全的。在整个孵育期内未检测到死亡率，表明支架无毒。尿囊素、槲皮素和咖啡酸的体外释放研究结果证实了支架同步释放的巨大潜力。氧化石墨烯/明胶/海藻酸盐支架是无创、双重模拟ECM和多靶点伤口治疗的有前途的候选者，为解决伤口愈合过程的复杂性提供了一种创新策略。
