Gao Zhongfei, Li Yulun, Li Xingwei, Chen Hongao, Li Chengbo, Xie Xianrui, Zhao Yuqing, Yan Huanhuan, Yang Zhengyou, Hou Guige
Department of Microbiology, College of Life Science, Key Laboratory for Agriculture Microbiology, Shandong Agricultural University, Tai'an 271018, PR China; School of Pharmacy, the Key Laboratory of Medical Antibacterial Materials of Shandong Province, Binzhou Medical University, Yantai 264003, PR China.
School of Pharmacy, the Key Laboratory of Medical Antibacterial Materials of Shandong Province, Binzhou Medical University, Yantai 264003, PR China.
Int J Biol Macromol. 2025 Mar;296:139737. doi: 10.1016/j.ijbiomac.2025.139737. Epub 2025 Jan 9.
Chronic wounds caused by microbial infection have emerged as a major challenge on patients and medical health system. Bacterial cellulose (BC) characterized by its excellent biocompatibility and porous network, holds promise for addressing complex wound issues. However, lack of inherent antibacterial activity and cross-linking sites in the molecular network of BC have constrained its efficacy in hydrogel design and treatment of bacterial-infected wounds. Additionally, few studies have explored the effects of precursor crosslinking sequences on hydrogel processing. Herein, a quaternary ammonium and aldehyde-biofunctionalized bacterial cellulose (OQBC) was synthesized and utilized for the development of double network (DN) hydrogels, incorporating the crosslinking sequences of thiol-alginate (SASH) and carboxymethyl chitosan (CMCS). Firstly, OQBC was characterized with bifunctional groups, which endows its inherent antibacterial activity and gel-forming property. Subsequently, DN hydrogels formed through thiol-aldehyde addition and amino-aldehyde reactions showed favorable injectability and self-healing ability. The sequential crosslinking via Schiff-base and thiohemiacetal bonds endowed the hydrogels with distinct features, including degradation behavior, pH-responsive swelling, water retention, surface roughness, and cell behavior. With the increasing OQBC content into hydrogels, bacteriostatic rate exceeded 90 % without obvious cytotoxicity. Hydrogels also exhibited antioxidant and sustained drug release properties. Moreover, in infected skin thickness defect rats, the selected hydrogel enhanced wound repair and regeneration by inhibiting inflammation and promoting collagen deposition and angiogenesis. This design of sequence-dependent crosslinked antibacterial DN hydrogel offers a promising tool for the development of advanced materials to treat infected wounds.
由微生物感染引起的慢性伤口已成为患者和医疗健康系统面临的一项重大挑战。细菌纤维素（BC）具有优异的生物相容性和多孔网络结构，有望解决复杂的伤口问题。然而，BC分子网络中缺乏固有的抗菌活性和交联位点，限制了其在水凝胶设计和治疗细菌感染伤口方面的功效。此外，很少有研究探讨前体交联序列对水凝胶加工的影响。在此，合成了一种季铵和醛双功能化细菌纤维素（OQBC），并将其用于开发包含硫醇-海藻酸盐（SASH）和羧甲基壳聚糖（CMCS）交联序列的双网络（DN）水凝胶。首先，对OQBC进行了双功能基团表征，赋予其固有的抗菌活性和成胶性能。随后，通过硫醇-醛加成和氨基-醛反应形成的DN水凝胶表现出良好的可注射性和自愈能力。通过席夫碱和硫代半缩醛键的顺序交联赋予了水凝胶独特的特性，包括降解行为、pH响应性溶胀、保水性、表面粗糙度和细胞行为。随着水凝胶中OQBC含量的增加，抑菌率超过90%且无明显细胞毒性。水凝胶还表现出抗氧化和药物缓释性能。此外，在感染性皮肤厚度缺损大鼠中，所选水凝胶通过抑制炎症、促进胶原蛋白沉积和血管生成，增强了伤口修复和再生。这种序列依赖性交联抗菌DN水凝胶的设计为开发用于治疗感染伤口的先进材料提供了一种有前景的工具。
