Bioinspired Nanofibrous Glycopeptide Hydrogel Dressing for Accelerating Wound Healing: A Cytokine‐Free, M2‐Type Macrophage Polarization Approach

Abstract Wound management remains a major concern in clinical care. Conventional dressings and hydrogels delivering drugs or cells can drive wound healing. However, these approaches are limited either by unnecessary bleeding and tissue tearing, or sophisticated fabrication, high cost, and drug‐related side effects. Herein, a novel bioinspired glycopeptide hydrogel is rationally designed to mimic the glycoprotein components and nanofibrous architecture of cutaneous extracellular matrix (ECM) for self‐accelerating the wound healing by regulating macrophage polarization without any additional therapeutic agents. The glycopeptide hydrogel, termed as GM‐peptide hybrid hydrogel (GP gel ), is established by the self‐assembly of β‐sheet Q11 peptide‐grafted glucomannan, with nanofibrous structure, high water content, porosity, and self‐healing properties. It is observed that GP gel displays remarkable capability of polarizing primary macrophages to M2‐type phenotype in vitro and in vivo by inducing the activation of mannose receptors through ERK/STAT6 pathway. GP gel unprecedentedly expedites the wound closure rate and the regeneration of epidermis tissues in full‐thickness skin excision models without drugs, exogenous cytokines, or seeded cells. More significantly, GP gel could promote angiogenesis in the repaired skin tissues. Collectively, such a novel ECM‐mimicking glycopeptide hydrogel provides a highly effective treatment approach for skin wounds and may serve as a promising scaffold in regenerative medicine.