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.
Wound repair is a complex and dynamic process, involving stages of hemostasis, inflammation, proliferation, and remodeling. Standard methods currently used for clinical treatment of skin defects remain unsatisfying and alternative treatments have emerged including acupuncture mostly relying on the conventional needle method. It is applied sustained acupuncture therapy with bioengineered stem cell-loaded hydrogel microspheres (A-SGC), where the data gathered through transcriptomics, metabolomics, and single-cell omics analyses are used to construct a comprehensive multi-omics map underlying the wound regeneration process with such a therapy. Under the treatment of A-SGC, the interactions and Yin-Yang balance among fibroblasts, macrophages, endothelial cells, and keratinocytes facilitated skin regeneration instead of scarred healing. The genes related to the promotion of matrix synthesis and re-epithelialization played important roles in the transition from the inflammatory granulation phase to the stromal remodeling phase. This convergence use of hydrogel microspheres, stem cells, and sustained acupuncture therapy could have previously unattainable therapeutic implications for improved wound treatment.
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