From bug to bubble: the rising prominence of Lactobacillus-derived extracellular vesicles as postbiotic wound healers.

The therapeutic landscape of probiotics is undergoing a paradigm shift from the live bacteria "bug" to the bioactive extracellular vesicles (EVs) "bubble" they secrete. Owing to their essential defense and metabolic functions, EVs derived from Lactobacillus, a genus of anaerobic or microaerophilic probiotics well known for their ability to ferment carbohydrates into lactic acid, have garnered particular interest for wound healing. As such, the presented mini-review began by elucidating why these Lactobacillus-derived EVs (L-EVs) attract upward attention by highlighting their superior safety, stability, multifunctionality, customizability, and scalability. This was followed by elaborating how these L-EVs accelerate wound healing by detailing their multifaceted mechanisms, including removing bacteria, reprogramming the microenvironment, repairing tissue, and remodeling the matrix during the wound-healing process. Lastly, it ended by envisioning where these L-EVs head for future therapy by addressing the translational hurdles, such as the lack of isolation and purification standardizations, the existing cargo and batch variabilities, as well as the ambiguous classification and regulation of L-EVs, which must be overcome to push them from bench to bedside. Moreover, it further proposed a specialized database based on artificial intelligence and multi-omics, the combined modification based on diverse engineering approaches, as well as the advanced formulation based on the material engineering strategies of L-EVs in the future to integrate the next generation of wound management modalities with optimal treatment efficacy.