Zayed Aya M, Hussein Ahmed A, Sabra Sally A
Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria 21526, Egypt.
Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria 21526, Egypt.
Int J Biol Macromol. 2025 Sep;322(Pt 3):146895. doi: 10.1016/j.ijbiomac.2025.146895. Epub 2025 Aug 14.
Wound healing is an integrative biological process with overlapping phases including, inflammation, granulation, and tissue remodeling. A potent wound dressing should be multifunctional with anti-inflammatory, antioxidant and tissue regeneration activities. Hydrogel films comprised of natural polymers are one of the best matrices that can be used to co-encapsulate multiple active molecules. In this context, alginate/pectin (ALG//PEC) hydrogel incorporating atorvastatin (ATR) and Jacaranda mimosifolia (J. mimosifolia) leaf extract was synthesized via solvent casting ionotropic gelation technique. The dual-loaded hydrogel film was characterized in terms of its chemical composition, tensile strength, in vitro drug release, hemocompatibility, and in vivo wound healing efficiency. Fourier-transform infrared (FTIR) analysis showed that the drug and the herbal extract were successfully incorporated without any chemical interaction. In addition, both blank hydrogel film and ATR/J. mimosifolia hydrogel film exhibited tensile strength of about 20.24 ± 0.66 and 21.68 ± 1.18 MPa, respectively and strain values of 68.73 ± 2.32 and 61.3 ± 1.06 %, respectively, which were suitable for wound dressing application. Moreover, in vitro drug release study indicated initial burst release of both ATR and J. mimosifolia reaching 34.87 % and 30.24 %, respectively after 2 h, then they reached 91.1 % and 50.23 %, respectively after 24 h, with ATR released at a faster rate in comparison to the herbal extract. When the dual-loaded hydrogel film was incubated with red blood cells, it displayed hemolytic potential of about 1.665 ± 0.063 %, which was comparable to blank hydrogel film 1.76 ± 0.035 %, showing excellent hemocompatibility. More importantly, in vivo studies in a rat model revealed that dual-loaded hydrogel film exhibited a superior wound closure in comparison to sterile gauze and blank hydrogel film-treated groups with the least inflammation and the highest collagen deposition. Furthermore, immucohistological investigation of CD31 as an angiogenic marker showed that dual-loaded hydrogel film displayed the highest expression level in comparison to all other treated groups, conforming that this dual-loaded hydrogel film could serve as a potential wound dressing film with anti-inflammatory and angiogenesis effects.
伤口愈合是一个综合性的生物学过程，具有炎症、肉芽形成和组织重塑等重叠阶段。一种有效的伤口敷料应具有抗炎、抗氧化和组织再生等多种功能。由天然聚合物组成的水凝胶薄膜是可用于共包封多种活性分子的最佳基质之一。在此背景下，通过溶剂浇铸离子凝胶化技术合成了负载阿托伐他汀（ATR）和蓝花楹叶提取物的藻酸盐/果胶（ALG//PEC）水凝胶。对这种双负载水凝胶薄膜进行了化学成分、拉伸强度、体外药物释放、血液相容性和体内伤口愈合效率等方面的表征。傅里叶变换红外光谱（FTIR）分析表明，药物和草药提取物已成功包封，且无任何化学相互作用。此外，空白水凝胶薄膜和ATR/蓝花楹水凝胶薄膜的拉伸强度分别约为20.24±0.66和21.68±1.18MPa，应变值分别为68.73±2.32%和61.3±1.06%，均适用于伤口敷料应用。此外，体外药物释放研究表明，ATR和蓝花楹叶提取物在2小时后的初始突释率分别达到34.87%和30.24%，24小时后分别达到91.1%和50.23%，与草药提取物相比，ATR的释放速率更快。当双负载水凝胶薄膜与红细胞孵育时，其溶血率约为1.665±0.063%，与空白水凝胶薄膜的1.76±0.035%相当，显示出优异的血液相容性。更重要的是，在大鼠模型中的体内研究表明，与无菌纱布和空白水凝胶薄膜处理组相比，双负载水凝胶薄膜表现出更好的伤口闭合效果，炎症最少，胶原蛋白沉积最高。此外，作为血管生成标志物的CD31免疫组织学研究表明，与所有其他处理组相比，双负载水凝胶薄膜的表达水平最高，这表明这种双负载水凝胶薄膜可作为一种具有抗炎和血管生成作用的潜在伤口敷料薄膜。
