Larijani Ghazaleh, Lotfi Abolfazl, Barati Shirin, Janzadeh Atousa, Abediankenari Saeid, Faghihi Faezeh, Amini Naser
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
J Mol Histol. 2025 Jul 12;56(4):225. doi: 10.1007/s10735-025-10508-1.
Diabetic ulcers often result from a combination of ischemia and oxidative stress, which are exacerbated by inflammation in the wound. Quercetin (3,3',4',5,7-pentahydroxyflavone), a flavonoid with well-documented antioxidant and anti-inflammatory properties, has garnered significant attention in the field of skin regeneration. In addition, chitosan/alginate (C/A) wound dressings have been shown to create a conducive environment for wound healing, leveraging the antimicrobial and anti-inflammatory properties of chitosan, as well as the hydrogel and water-absorbing properties of alginate. Thus, the development of a biologic scaffold, such as quercetin-loaded C/A, may offer a promising alternative for diabetic wound treatment, providing a dermal structure that supports wound healing. In this study, a chitosan-alginate hydrogel was prepared and loaded with varying concentrations of quercetin (0.03%, 0.1%, and 0.3% w/v). Following in vitro evaluation using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), MTT assay, and swelling and degradation tests, the prepared dressings were applied to rats with diabetic wounds, and the resulting scars were analyzed histologically after a 2-week period. The FTIR spectra of the C/A hydrogels revealed characteristic absorption bands corresponding to specific functional groups, including hydroxyl (O-H), amine (N-H), and alkene (C=C) groups. Scanning electron microscopy (SEM) analysis demonstrated successful blending of the hydrogels and adequate cell adhesion. The MTT assay results indicated no significant differences in cellular metabolic activity among the groups. The water uptake levels reached a plateau after 240 min across all experimental groups, suggesting a saturation point in water absorption capacity. The degradation rate of the hydrogel increased substantially from day 1 to day 7, with no significant differences observed among the groups, regardless of quercetin loading. A marked increase in re-epithelialization and collagen deposition was observed across all groups at day 14 compared to day 7, although no significant differences were detected between the quercetin-treated groups and the control or C/A groups. The reduction in wound diameter was significantly greater in the quercetin-treated groups compared to the control and C/A groups at day 14 (p < 0.05). Although our quercetin-loaded chitosan/alginate (2:1) wound dressing did not exhibit significant benefits in terms of re-epithelialization or collagen deposition, it did demonstrate efficacy in reducing wound diameter in diabetic rats.
糖尿病溃疡通常是由缺血和氧化应激共同导致的，而伤口处的炎症会加剧这些情况。槲皮素（3,3',4',5,7-五羟基黄酮）是一种具有充分文献记载的抗氧化和抗炎特性的类黄酮，在皮肤再生领域引起了广泛关注。此外，壳聚糖/海藻酸盐（C/A）伤口敷料已被证明能利用壳聚糖的抗菌和抗炎特性以及海藻酸盐的水凝胶和吸水特性，为伤口愈合创造有利环境。因此，开发一种生物支架，如负载槲皮素的C/A，可能为糖尿病伤口治疗提供一种有前景的替代方案，提供支持伤口愈合的真皮结构。在本研究中，制备了壳聚糖-海藻酸盐水凝胶，并负载不同浓度的槲皮素（0.03%、0.1%和0.3% w/v）。在使用傅里叶变换红外光谱（FTIR）、扫描电子显微镜（SEM）、MTT法以及溶胀和降解测试进行体外评估后，将制备的敷料应用于患有糖尿病伤口的大鼠，并在2周后对形成的疤痕进行组织学分析。C/A水凝胶的FTIR光谱显示出对应于特定官能团的特征吸收带，包括羟基（O-H）、胺基（N-H）和烯烃（C=C）基团。扫描电子显微镜（SEM）分析表明水凝胶成功混合且细胞黏附良好。MTT法结果表明各实验组之间细胞代谢活性无显著差异。所有实验组在240分钟后吸水率达到平稳状态，表明吸水能力达到饱和点。水凝胶的降解率从第1天到第7天大幅增加，各实验组之间未观察到显著差异，无论槲皮素负载量如何。与第7天相比，在第14天所有组的再上皮化和胶原蛋白沉积均显著增加，尽管槲皮素处理组与对照组或C/A组之间未检测到显著差异。在第14天，槲皮素处理组与对照组和C/A组相比，伤口直径的减小更为显著（p < 0.05）。尽管我们负载槲皮素的壳聚糖/海藻酸盐（2:1）伤口敷料在再上皮化或胶原蛋白沉积方面未表现出显著益处，但它在减小糖尿病大鼠伤口直径方面确实显示出疗效。
