Macrophage polarization and phenotypic switching have a significant impact on the immune microenvironment of wounds, making them crucial for wound healing. Creating immune-adapted microenvironment throughout the wound repair process by regulating macrophage polarization supports rapid wound healing. We explored the segmented use of M1-polarizing and M2-polarizing materials at different healing stages and found that this combination can significantly shorten the healing time. The macrophage polarization could be adjusted to M1 phenotype and M2 phenotype by selective modification of chitosan with dicyandiamide or polyethylene glycol, respectively. In a rat full-thickness infected wound model, combining dicyandiamide modified chitosan (DICY-CS) for M1 macrophage polarization in the inflammatory phase and PEGylated chitosan (PEG-CS) for M2 macrophage polarization in the proliferative phase significantly reduced wound healing time. A higher degree of re-epithelialization, collagen deposition and neovascularization were observed in wounds treated with this combination approach compared to the antimicrobial agents Silvadene and DICY-CS or PEG-CS alone. The use of different macrophage polarizing materials separately in different healing stages provided an optimal immune microenvironment and accelerated wound healing. This strategy provides a more comprehensive understanding of the wound healing process. It will be a new insight for the treatment of more complex and difficult-to-heal wounds such as pressure ulcers and diabetic wounds.
A continuously stable moist healing environment is immensely beneficial for wound healing, which can be availably achieved by providing an in situ hydrogel with enough strength resembling skin tissue and self-healing ability. Herein, through a dual-crosslinking strategy, hyaluronic acid-based hydrogels with excellent self-healing capacity and enhanced mechanical properties are fabricated via the acylhydrazone linkages and subsequent photocrosslinking based on hydrazide-modified sodium hyaluronate and aldehyde-modified maleic sodium hyaluronate. The hydrogels demonstrate the fast gelation process (< 1 min), the controlled swelling behaviors, and the good biocompatibility. Notably, they possess enhanced mechanical strength similar to the human dermis (~ 2.2 kPa). Also, they can self-heal rapidly with a self-healing efficiency of ~90 % at 6 h. Based on this, the hyaluronic acid-based hydrogels, without any biological factors involved, can facilitate the full-thickness skin wound reconstruction process by accelerating the three phases of the wound repair, including reducing wound inflammation in the inflammatory phase, promoting angiogenesis in the proliferative phase, and promoting the deposition and reconstruction of collagen in the remodeling phase. The produced hyaluronic acid hydrogel can serve as an ideal candidate for wound healing.
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