Multi-comparted microgels delivering human derived probiotics and deferoxamine for multidrug-resistant infection and healing

Abstract

Infection and vascular dysfunction are two major reasons for delayed wound healing, especially in the scenario of multidrug-resistant bacterial has been a challenge for antibiotics usage. Probiotics are effective in fighting pathogens, while avoiding the destruction of skin microbiome. However, the viability of probiotics is a major obstacle in clinical application. As a non-protein proangiogenic drug, deferoxamine (DFO) has significant advantages over traditional growth factors in terms of cost, storage and transportation conditions, and stability. However, there is still a problem of short half-life that requires reliable drug delivery carriers to maximize its effect. Here, we developed multiple-chambered microgels using electrospray and microfluidics. Lactobacillus fermentum (LF) and DFO, respectively, for the management of multidrug-resistant Pseudomonas aeruginosa (MPA) and promotion of wound healing. We first tested five probiotics isolated from healthy people and found LF inhibiting the growth of MPA by lowering local pH and antimicrobial substances. The multi-chambered microgels effectively inhibited MPA by delivering probiotics, they can also protect probiotics from antibiotics. DFO promoted the angiogenesis of human umbilical venous endothelial cells. The microgel system had good biocompatibility and hemocompatibility. In a MPA infected wound, the microgel system effectively alleviated wound infection by 87.44%, improved angiogenesis by 29.32% and accelerated wound healing. This work suggests that multi-compartmented microgels loaded with probiotics and deferoxamine have great potential in wounds with multidrug-resistant bacteria.