Bacterial infection remains a major barrier to effective wound healing by disrupting immune homeostasis, sustaining chronic inflammation, and impairing tissue regeneration. Herein, we present a green, sustainable strategy for fabricating antibacterial, immunomodulatory bioactive granular hydrogels (GHs) for infected wound regeneration. An amino-alcohol ether prepolymer (MP) was first synthesized via epoxy–amine click chemistry and subsequently complexed with the natural polyphenol tannic acid (TA), thereby triggering phase-separation-driven supramolecular self-assembly into GHs without additional crosslinkers. To elucidate the polymer assembly mechanism and identify the bioactive concentration threshold, agarose was introduced as a fourth component to construct A/MP@TA GHs. The results showed that increasing the agarose content progressively transformed the granular architecture into a sheet-like network, whereas A/MP@TA3, which represents the lowest agarose ratio that preserves the granular morphology, exhibited potent antibacterial and antioxidant activities, and enhanced fibroblast migration. In a bacteria-infected wound, A/MP@TA3 still markedly accelerated wound closure while promoting collagen deposition and angiogenesis. Mechanistically, sustained TA release reprogrammed the microenvironment by activating the KEAP1/Nrf2/HO-1 and suppressing NF-κB signaling, thereby driving macrophage polarization toward a pro-regenerative M2 phenotype. This work establishes a simple, cost-effective, and environmentally friendly platform for fabricating multifunctional hydrogel dressings and provides a biomaterial-based strategy for remodeling the immune microenvironment.
Wound status monitoring has emerged as a promising strategy to enable timely intervention for effective wound infection management and promote wound healing. Herein, a recyclable alginate hydrogel film with pH-sensing and antibacterial functions is developed as a smart wound dressing. The hydrogel film (SA-Anth) was fabricated via a two-step process, i.e., an evaporation-induced self-assembly of sodium alginate solution doped with anthocyanin and glycerin, followed by Ca2+-mediated ionic cross-linking using CaCl2. Taking advantage of the pH-responsiveness of anthocyanin, the hydrogel film exhibited distinct color changes from red-purple at pH 5.0 to violet-blue at pH 7.3 and further to green at pH 9.0, suggesting its potential for visual monitoring of wound pH variations associated with infection. The incorporation of anthocyanin endowed the film with antibacterial activity, achieving bacterial reduction rates of 90.48% against E. coli and 98.10% against S. aureus. The hydrogel film also exhibited wound-dressing-relevant properties, including appropriate physicochemical performance, a low hemolysis ratio, and good in vitro cytocompatibility. In an S. aureus-infected rat full-thickness wound model, SA-Anth treatment enhanced wound closure and improved histological features of tissue repair compared with the control treatments. Furthermore, the de-crosslinking of the ionically crosslinked network was triggered by the addition of EDTA, enabling the recovery of the alginate component. The SA-Anth hydrogel film integrates pH-responsive visual indication, antibacterial activity, favorable biocompatibility, infected-wound repair performance, and EDTA-assisted material recovery, providing a promising platform for intelligent wound-dressing applications.
Xi-Xi Zhu, Ying Feng, Hai-Qi Zhang et al.· International Journal of Bio...· 0 citations