Interaction between bacterial species is through quorum sensing (QS), a process that regulates and coordinates genes in virulence activities and biofilm formation. QS contributes to the slowdown of tissue repair during the wound healing process by inducing chronic inflammation of the wound. Here, we developed a multifunctional QS inhibitor based on a bioactive hydrogel system to interrupt the QS of bacteria, relieve hypoxia, and destroy biofilms, and thus accelerate the healing of infected wounds in diabetic mice. We loaded berberine (BBR, a QS inhibitor, and antibacterial agent) into a natural living microalgae Spirulina platensis (SP) to form a bioactive hydrogel (BBR@SP gel) in combination with carboxymethyl chitosan/sodium alginate. Under laser irradiation, the BBR@SP gel could constantly release BBR and produce reactive oxygen species, resulting in a synergistic QS inhibition against methicillin-resistant Staphylococcus aureus (MRSA) combined chemo-photodynamic therapy. The BBR@SP gel also suppresses and destroys biofilm formation and down-regulates the expression of virulence factors. We found that the BBR@SP gel could accelerate MRSA-infected diabetic wound healing by promoting angiogenesis, skin regeneration, and suppressing the inflammatory response. Our work presents an innovative antimicrobial strategy that eliminates drug-resistant bacteria by synergistic chemo-photodynamic killing effect, relieving biofilm hypoxia, and blocking QS simultaneously, which may open up new prospects in solving antimicrobial drug resistance and combating biofilm-related infections.

细菌物种之间的相互作用是通过群体感应 (QS) 进行的，这是一个在毒力活动和生物膜形成中调节和协调基因的过程。QS 通过诱导伤口的慢性炎症，在伤口愈合过程中减缓组织修复。在这里，我们开发了一种基于生物活性水凝胶系统的多功能 QS 抑制剂，可中断细菌的 QS，缓解缺氧并破坏生物膜，从而加速糖尿病小鼠感染伤口的愈合。我们将小檗碱（BBR，一种 QS 抑制剂和抗菌剂）加载到天然微藻螺旋藻中(SP) 与羧甲基壳聚糖/海藻酸钠结合形成生物活性水凝胶 (BBR@SP 凝胶)。在激光照射下，BBR@SP凝胶可以不断释放BBR并产生活性氧，从而对耐甲氧西林金黄色葡萄球菌产生协同QS抑制作用(MRSA) 联合化学光动力疗法。BBR@SP 凝胶还抑制和破坏生物膜形成并下调毒力因子的表达。我们发现 BBR@SP 凝胶可以通过促进血管生成、皮肤再生和抑制炎症反应来加速 MRSA 感染的糖尿病伤口愈合。我们的工作提出了一种创新的抗菌策略，通过协同化学光动力杀伤作用消除耐药菌，缓解生物膜缺氧，同时阻断 QS，这可能为解决抗菌药物耐药性和对抗生物膜相关感染开辟新的前景。