Wound Healing: From Foundational Research to Innovations in Therapeutic Design

Junxiao ZhangShenglin GengGuojuan FanJinlong Ma^*

• Shandong Second Medical University, Weifang, China

emission of harmful UV radiation contradict the established principles of moist wound healing, thereby restricting its therapeutic utility. The ebook further presents nine original research articles that introduce innovative, mechanism-driven solutions for wound repair. In the realm of biomaterial engineering, one study reports a novel double-cross-linked PDGA hydrogel (comprising polyacrylamide, dopamine-grafted sodium alginate, glycidyl methacrylate-grafted gelatin, and Angelica sinensis polysaccharide), which rapidly forms in situ, acts as a protective barrier, and accelerates healing through rapid hemostasis, enhanced cell proliferation, collagen deposition, and angiogenesis [7] . Another study combines biomaterials with stem cell-derived exosomes by constructing rIGF1-enriched exosomes delivered via a silk fibroin-collagen hydrogel, effectively promoting annulus fibrosus wound repair and attenuating intervertebral disc degeneration in rats by stimulating cell proliferation and migration [8] . To address bacterial infection-related impairments, a multifunctional nanoplatform (P(H)ZPAg) was developed by embedding palladium hydride into a ZIF-8 framework, modifying its surface with polydopamine, and generating silver nanoparticles in situ. This system enables synergistic antibacterial action through controlled hydrogen release, photothermal conversion, and Ag⁺ activity, collectively accelerating wound healing in infected models [9] . Separately, a traditional herbal formula (BaDuShengJi San) was reformulated into a stable carbomer-based hydrogel, which significantly enhanced its antibacterial efficacy (MIC 64 μg/mL), accelerated diabetic wound reepithelialization by 40%, and reduced its inherent renal toxicity [10] . Beyond biomaterial innovations, several studies focus on bioactive compounds and peptides. Nervonic acid, a key component of myelin and nerve cell membranes, was shown to uniquely synchronize neurogenesis and angiogenesis, enabling holistic repair of both neural and vascular tissues [11] . Thymoquinone, a natural quinone, enhanced skin flap survival by 44% through dual regulation of SIRT1/NF-κB-mediated pyroptosis and pro-angiogenic activity, providing a synergistic countermeasure to ischemiareperfusion injury [12] . The human antimicrobial peptide LL37, the sole cathelicidinderived peptide in humans, not only exerts broad-spectrum microbicidal and immunomodulatory effects but also acts as a potent angiogenic agent by activating the VEGFA-PI3K/AKT/mTOR pathway, suggesting new translational avenues from antimicrobial to ischemic wound therapy [13] . Another investigation revealed that narirutin, a citrus-derived flavonoid, accelerates diabetic wound healing by reprogramming macrophage metabolism via the AMPK/Mfn2 axis, shifting energy metabolism from glycolysis to oxidative phosphorylation, promoting M1-to-M2 polarization, and resulting in a 58% improvement in wound closure [14] . In preclinical therapeutic development, the combination of sodium houttuyfonate with penicillin G demonstrated strong synergy against MRSA-infected wounds, reducing bacterial load by 91% and lowering key inflammatory cytokines (IL-6, TNF-α) by 50% in rat models, offering a viable alternative for combating drug-resistant infections [15] . Collectively, this ebook offers a holistic perspective on current advances in wound management. The two review articles establish essential background, the opinion piece provides a critical outlook on antibacterial technology, and the nine original research papers deliver actionable, mechanism-based solutions. We extend our gratitude to all contributing authors for their rigorous work and to the editorial team for their dedicated efforts. It is our hope that this collection will foster cross-disciplinary collaboration, accelerate the translation of novel strategies into clinical practice, and, ultimately, improve outcomes for patients suffering from refractory wounds.