School of Medicine, Ningbo University, Ningbo 315010, China.
ACS Biomater Sci Eng. 2021 Sep 13;7(9):4557-4568. doi: 10.1021/acsbiomaterials.1c00600. Epub 2021 Aug 23.
A series of hydrogels containing guanidine-based polymers using a poloxamer as the matrix were prepared to provide novel wound dressings with antibacterial and repairing-promotion properties for skin wounds. Herein, we developed a series of antibacterial hydrogels, the cationic guanidine-based polymer polyhexamethylene guanidine hydrochloride (PHMG) with poloxamer aqueous solution (12%, w/w) simplified as PHMGP, chitosan (CS)-cross-linked PHMG (referred to as PHMC) with poloxamer aqueous solution simplified as PHMCP, and hyaluronic acid (HA)-modified PHMG (referred to as PHMH) with poloxamer aqueous solution simplified as PHMHP, for enhancing full-thickness skin wound healing. The characterizations, antimicrobial activity, cytotoxicity, and in vivo full-thickness wound-healing capability of these hydrogels were analyzed and evaluated. The results show that though PHMGP possesses great bactericide properties, its cytotoxicity is too strong to support skin regeneration. However, after modified with CS or HA, PHMCP and PHMHP showed good biocompatibility and antimicrobial properties against Gram-positive and Gram-negative bacteria that are commonly present in injured skin. Both PHMCP and PHMHP hydrogels exhibited upgraded wound-healing efficiency in full-thickness skin defects, characterized by a shorter wound closure time, faster re-regeneration, and the earlier formation of skin appendages, compared with those of control or pure poloxamer treatments. Their biological mechanism was detected. Both PHMCP and PHMHP can regulate the related biofactors during the skin repair process such as interleukin-1β (IL-1β), interleukin-6 (IL-6), transforming growth factor beta-1(TGF-β1), alpha-smooth muscle actin (α-SMA), and vascular endothelial growth factor, to promote wound healing with less serious scarring. In short, hydrogels with excellent capabilities to inhibit microorganism infection and promote wound healing were developed, which will shed light on designing and producing wound dressings with promising applications in future.
一系列含有胍基聚合物的水凝胶，以泊洛沙姆为基质，旨在为皮肤伤口提供具有抗菌和促进修复性能的新型伤口敷料。在此，我们开发了一系列抗菌水凝胶，将阳离子胍基聚合物盐酸聚六亚甲基胍（PHMG）与泊洛沙姆水溶液（12%，w/w）简单地称为 PHMGP，壳聚糖（CS）交联 PHMG（简称 PHMC）与泊洛沙姆水溶液简单地称为 PHMCP，以及透明质酸（HA）修饰的 PHMG（简称 PHMH）与泊洛沙姆水溶液简单地称为 PHMHP，以增强全层皮肤伤口愈合。分析和评估了这些水凝胶的特性、抗菌活性、细胞毒性和体内全层伤口愈合能力。结果表明，尽管 PHMGP 具有很强的杀菌性能，但它的细胞毒性太强，不利于皮肤再生。然而，经过 CS 或 HA 修饰后，PHMCP 和 PHMHP 表现出良好的生物相容性和对革兰氏阳性和革兰氏阴性细菌的抗菌性能，这些细菌通常存在于受伤的皮肤中。与对照或纯泊洛沙姆处理相比，PHMCP 和 PHMHP 水凝胶在全层皮肤缺损中表现出更高的伤口愈合效率，表现为伤口闭合时间更短、更快的再生和更早的皮肤附属物形成。检测了它们的生物学机制。PHMCP 和 PHMHP 都可以调节皮肤修复过程中的相关生物因子，如白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、转化生长因子β-1（TGF-β1）、α-平滑肌肌动蛋白（α-SMA）和血管内皮生长因子，以促进伤口愈合，减少严重的疤痕形成。总之，开发了具有抑制微生物感染和促进伤口愈合能力的水凝胶，这将为设计和生产具有广阔应用前景的伤口敷料提供启示。
