关键词: Antibiotic alternatives Carboxymethyl chitosan Hydrogels Metal–organic framework Nitric oxide Wound healing

Mesh : Hydrogels / chemistry pharmacology Wound Healing / drug effects Anti-Bacterial Agents / pharmacology chemistry Chitosan / chemistry analogs & derivatives pharmacology Animals Nitroprusside / pharmacology chemistry Mice Reactive Oxygen Species / metabolism Humans Silver / chemistry pharmacology Nanoparticles / chemistry Wound Infection / drug therapy Escherichia coli / drug effects Staphylococcus aureus / drug effects

来  源:   DOI:10.1186/s12951-024-02657-4   PDF(Pubmed)

Abstract:
Skin wound infection has become a notable medical threat. Herein, the polysaccharide-based injectable hydrogels with multifunctionality were developed by a simple and fast gelation process not only to inactivate bacteria but also to accelerate bacteria-infected wound healing. Sodium nitroprusside (SNP) loaded PCN-224 nanoparticles were introduced into the polymer matrix formed by the dynamic and reversible coordinate bonds between Ag+ with carboxyl and amino or hydroxyl groups on carboxymethyl chitosan (CMCS), hydrogen bonds and electrostatic interactions in the polymer to fabricate SNP@PCN@Gel hydrogels. SNP@PCN@Gel displayed interconnected porous structure, excellent self-healing capacity, low cytotoxicity, good blood compatibility, and robust antibacterial activity. SNP@PCN@Gel could produce reactive oxygen species (ROS) and NO along with Fe2+, and showed long-term sustained release of Ag+, thereby effectively killing bacteria by synergistic photothermal (hyperthermia), photodynamic (ROS), chemodynamic (Fenton reaction), gas (NO) and ion (Ag+ and -NH3+ in CMCS) therapy. Remarkably, the hydrogels significantly promoted granulation tissue formation, reepithelization, collagen deposition and angiogenesis as well as wound contraction in bacteria-infected wound healing. Taken together, the strategy represented a general method to engineer the unprecedented photoactivatable \"all-in-one\" hydrogels with enhanced antibacterial activity and paved a new way for development of antibiotic alternatives and wound dressing.
摘要:
皮肤伤口感染已成为一种显著的医学威胁。在这里,具有多功能的基于多糖的可注射水凝胶是通过简单而快速的凝胶化过程开发的,不仅可以灭活细菌,而且可以加速细菌感染的伤口愈合。将硝普钠(SNP)负载的PCN-224纳米颗粒引入由羧甲基壳聚糖(CMCS)上的Ag与羧基和氨基或羟基之间的动态和可逆配位键形成的聚合物基质中,聚合物中的氢键和静电相互作用制备SNP@PCN@Gel水凝胶。SNP@PCN@凝胶显示互连多孔结构,良好的自我修复能力,低细胞毒性,良好的血液相容性,和强大的抗菌活性。SNP@PCN@Gel能与Fe2+一起产生活性氧(ROS)和NO,并显示长期持续释放Ag+,从而有效地杀死细菌通过协同光热(热疗),光动力(ROS),化学动力学(芬顿反应),气体(NO)和离子(Ag+和-NH3+在CMCS)治疗。值得注意的是,水凝胶显著促进肉芽组织形成,上皮再生,细菌感染伤口愈合中的胶原沉积和血管生成以及伤口收缩。一起来看,该策略代表了一种通用方法,可以设计出具有增强抗菌活性的前所未有的可光活化的“多合一”水凝胶,并为开发抗生素替代品和伤口敷料铺平了一条新途径。
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