抗菌肽HHC-36和分散素B共递释可注射水凝胶的构建及其多维防治假体感染的研究

The challenge of titanium alloy prosthesis infection and biofilm formation needs to be solved urgently. Injectable hydrogel drug delivery system has made it possible to effectively meet this challenge. In this study, we will copolymerize norbornene and tetrazine groups respectively on gelatin. Based on the Diels-Alder chemical reaction between the latter two, an injectable gelatin hydrogel antimicrobial peptide (HHC-36) and dispersin B co-delivery system will be constructed, which will disperse biofilm, inhibit the formation of biofilm and participate in immune regulation of antibacterial properties. The project will focus on the injectable co-delivery hydrogel‘s bactericidal effect to Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus epidermidis and Escherichia col. Moreover, in vitro and in vivo detection of anti-biofilm and biofilm lysis performance will be analyzed based on mature models, and the synergistic anti-biofilm effect of antimicrobial peptides and dispersin B will be studied. This injectable co-delivery hydrogel system can deliver disperse B and antimicrobial peptides to the precise target with a minimally invasive approach, the multi-dimensional collaborative sterilization, inhibition of biofilm formation and biofilm formation, avoiding the possibility of resurgence of infection, while prevent and treat prosthesis infection simultaneously. This disperse B and antimicrobial peptide co-release gelatin hydrogel will provide new ideas and innovative methods to prevention and treatment of prosthetic infection.

钛合金假体周围生物膜的形成通常造成感染迁延不愈，大面积清创和长期使用抗生素治疗的代价巨大，如何微创和高效攻克生物膜是亟待解决的一大挑战。本项目拟在前期基础上，利用Diels-Alder 链接化学反应构建可注射明胶水凝胶，负载有效裂解生物膜的分散素B和能高效广谱杀菌的抗菌肽HHC-36并实现共递释。通过体内外系统检测共递释水凝胶杀菌、免疫调控、抗生物膜和裂解生物膜的性能，验证分析抗菌肽和分散素B抗生物膜的协同作用和探索其潜在机制。该可注射共递释水凝胶体系可微创将分散素B和抗菌肽精准递送到靶点缓释，裂解生物膜并抑制生物膜形成，参与免疫激活，立体化多维协同杀菌，实现假体感染的防治一体化，为假体感染的有效防治提供新的突破。抗菌肽HHC-36和分散素B共递释可注射水凝胶的构建为防治生物膜提供了新思路和新方法，对假体感染的防治具有重要的科学指导和临床转化意义。

钛合金假体周围生物膜的形成通常造成感染迁延不愈，大面积清创和长期使用抗生素治疗的代价巨大，如何微创和高效攻克生物膜是亟待解决的一大挑战。本项目拟在前期基础上，利用Diels-Alder链接化学反应构建可注射明胶水凝胶，负载有效裂解生物膜的分散素B和能高效广谱杀菌的抗菌肽HHC-36并实现共递释。通过体内外系统检测共递释水凝胶杀菌、免疫调控、抗生物膜和裂解生物膜的性能，验证分析抗菌肽和分散素B抗生物膜的协同作用和探索其潜在机制。该可注射共递释水凝胶体系可微创将分散素B和抗菌肽精准递送到靶点缓释，裂解生物膜并抑制生物膜形成，参与免疫激活，立体化多维协同杀菌 ，实现假体感染的防治一体化，为假体感染的有效防治提供新的突破。抗菌肽HHC-36和分散素B共递释可注射水凝胶的构建为防治生物膜提供了新思路和新方法，对假体感染的防治具有重要的科学指导和临床转化意义。