Background: Skin wound healing is a complex process requiring coordinated cellular and molecular interactions. Polynucleotides (PN) and hyaluronic acid (HA) have emerged as promising agents in regenerative medicine due to their ability to enhance cellular proliferation, angiogenesis, and extracellular matrix (ECM) remodeling. Combining PN and HA offers potential synergistic effects, accelerating wound repair.

Methods: PN and HA hydrogels were prepared and evaluated for viscosity and gel stability. Their effects on human dermal fibroblasts (HDF) and keratinocytes (HaCaT) were assessed using migration, proliferation assays, and gene expression analyses for vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and matrix metalloproteinase-10 (MMP-10). In vivo studies were conducted using a mouse wound model to observe wound closure and tissue regeneration over 14 days.

Results: The PN-HA mixture demonstrated superior mechanical stability compared to individual components. In vitro, PN-HA significantly enhanced HDF and HaCaT migration, proliferation, and upregulated VEGF, MMP-9, and MMP-10 expression. In vivo, PN-HA treatment accelerated wound closure, improved dermal thickness, and enhanced ECM remodeling, as evidenced by histological analyses.

Conclusion: The PN-HA combination synergistically accelerates wound healing by promoting angiogenesis, cellular migration, and ECM remodeling. These findings highlight its potential as an advanced wound dressing for acute and chronic wound management.

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http://dx.doi.org/10.1007/s13770-025-00712-1DOI Listing

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