Wound healing is a complex and precisely regulated process that encompasses multiple stages, including inflammation, anti-inflammation, and tissue repair. It involves various cells and signaling molecules, with macrophages demonstrating a significant degree of plasticity and playing a crucial regulatory role at different stages. In recent years, the use of biomaterials, which include both natural and synthetic polymers or macromolecules, has proliferated for the purpose of enhancing wound healing. This review summarizes how these diverse biomaterials promote wound healing by modulating macrophage behavior and examines the broader implications of these modulations. Additionally, we discuss the limitations associated with the clinical application of immunomodulatory biomaterials and propose potential solutions. Finally, we look towards future developments in the design of immunomodulatory biomaterials intended to enhance wound healing.

Wound healing is a multifaceted biological process that involves a series of cellular interactions and immune responses to restore tissue integrity following injury. Postbiotics, non-viable microbial products, have garnered increasing attention for their potential therapeutic applications in wound healing. This study investigated the efficacy of a postbiotic extract derived from Lactobacillus bulgaricus (L. bulgaricus) fermentation in promoting wound healing. The extract was prepared by controlled fermentation, followed by inactivation and purification. In vitro, we assessed antimicrobial properties against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Pseudomonas aeruginosa (P. aeruginosa) and performed peptidomic analysis to identify antimicrobial peptides. Effects on HaCaT proliferation, immune modulation, and collagen synthesis were evaluated. In vivo, a full-thickness S. aureus–infected wound model in C57BL/6 mice was used to assess wound closure and collagen deposition. Together, the in vitro and in vivo findings demonstrated antimicrobial, immunomodulatory, and regenerative activities, supporting composite postbiotics as a multifunctional wound-care approach.