Biofabricated macrophage and fibroblast membranes synergistically promote skin wound healing

Abstract

Effective skin wound healing is a complex process involving anti-inflammation, fibrosis, matrix reconstruction, and angiogenesis. This work aimed to integrate the macrophage-mediated anti-inflammation and fibroblast-assisted matrix reconstruction for enhanced skin wound healing. Herein, we utilized the cytomembranes derived from repolarized M2 macrophages and fibroblasts to prepare the natural biologics. Results showed that the inflammatory M1 macrophages were repolarized to M2 phenotype by the M2 macrophage cytomembranes. As a consequence, the cytomembranes of M2 macrophage could facilitate the wound closure in mice. Furthermore, the addition of fibroblast membranes to the macrophage cytomembranes contributed to a better matrix reconstruction, neovascularization and angiogenesis.Next, we used a transforming growth factor-β (TGF-β) inhibitor to attenuate cutaneous scar formation. Therefore, our modality could promote skin wound healing and effectively suppress scar formation in the preclinical murine skin wounds. The cytomembrane biologics might provide a biocompatible and versatile tool for wound healing.

“AMP plus”: Immunostimulant-Inspired Design Based on Chemotactic Motif-(PhHAhPH)n

“…Upon KWH 2 treatment, we detected an increase in the breakdown of the lump and an increase in granulation tissue and hyperproliferative epidermis around the lump at day 4 post-treatment. This indicates the contribution of KWH 2 to the dermal and epidermal repair. − Accumulating evidence suggests that macrophages play important roles during wound healing, ,, apart from their classical roles as scavenger cells that phagocytize invading pathogens. KWH 2 chemoattracts macrophages in vitro.…”

“…This indicates the contribution of KWH 2 to the dermal and epidermal repair. 62−64 Accumulating evidence suggests that macrophages play important roles during wound healing, 63,65,66 apart from their classical roles as scavenger cells that phagocytize invading pathogens. KWH 2 chemoattracts macrophages in vitro.…”

Biomaterials for immunomodulation in wound healing

“…In the early stages of healing, macrophages exhibit a pro-inflammatory phenotype, marked by the release of inflammatory cytokines, such as TNF-α, IL-1 and IL-6, ROS, and nitric oxide [ 42 , 43 ]. As the wound environment evolves, macrophages shift their phenotype to support angiogenesis and ECM deposition [ 44 , 45 ]. Key mediators in this transition include VEGF-A, insulin-like growth factor 1, PDGF and TGF-β, along with the MMP inhibitor tissue inhibitor of metalloproteinases 1 [ 45–47 ].…”

Advances in Zebrafish for Diabetes Mellitus with Wound Model

“…The proliferative phase overlaps with the inflammatory phase, during which new tissues, new blood vessels (angiogenesis), and matrix structures are activated to fill the wound [ 42 , 43 ]. The final remodeling stage increases the tensile strength of the extracellular matrix (ECM) and reduces the blood supply to the damaged area [ 21 , 44 , 45 ].…”