伤口愈合
干酪乳杆菌
益生菌
植物乳杆菌
体内
化学
体外
自愈水凝胶
细胞生物学
细菌
小泡
微生物学
生物
膜
乳酸
免疫学
生物化学
生物技术
有机化学
发酵
遗传学
作者
Thomas Kuhn,Ahmad Aljohmani,Nicolas Frank,Lina Zielke,Mina Mehanny,Matthias W. Laschke,Marcus Koch,Jessica Hoppstädter,Alexandra K. Kiemer,Daniela Yildiz,Gregor Fuhrmann
标识
DOI:10.1016/j.jconrel.2023.12.011
摘要
Probiotic bacteria, such as Lactobacilli, have been shown to elicit beneficial effects in various tissue regeneration applications. However, their formulation as living bacteria is challenging, and their therapeutic use as proliferating microorganisms is especially limited in immunocompromised patients. Here, we propose a new therapeutic avenue to circumvent these shortcomings by developing a bacteriomimetic hydrogel based on membrane vesicles (MVs) produced by Lactobacilli. We coupled MVs from Lactobacillus plantarum and Lactobacillus casei, respectively, to the surface of synthetic microparticles, and embedded those bacteriomimetics into a pharmaceutically applicable hydrogel matrix. The wound microenvironment changes during the wound healing process, including adaptions of the pH and changes of the oxygen supply. We thus performed proteomic characterization of the MVs harvested under different culture conditions and identified characteristic proteins related to the biological effect of the probiotics in every culture state. In addition, we highlight a number of unique proteins expressed and sorted into the MVs for every culture condition. Using different in vitro models, we demonstrated that increased cell migration and anti-inflammatory effects of the bacteriomimetic microparticles were dependent on the culture condition of the secreting bacteria. Finally, we demonstrated the bacteriomimetic hydrogel's ability to improve healing in an in vivo mouse full-thickness wound model. Our results create a solid basis for the future application of probiotic-derived vesicles in the treatment of inflammatory dispositions and stimulates the initiation of further preclinical trials.
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