Chitosan-Alginate Hydrogel Enriched with <i>Hypericum perforatum</i> Callus Extract for Improved Wound Healing and Scar Inhibition

<i>Hypericum perforatum</i> callus contains pluripotent stem cells, and its extract (HPCE) is a natural compound that includes various biologically active components, such as phenolic acids, flavonoids, and naphthodiantrons like hypericin and hyperforin. These components give HPCE significant antibacterial and antioxidant properties, making it a valuable option for wound healing. Unlike traditional wound dressings that may leave a residue or necessitate invasive procedures like phototherapy, HPCE is a promising alternative. This study presents a hydrogel wound dressing made from a chitosan/alginate scaffold loaded with HPCE (CA/HPCE). This system displayed remarkable mechanical properties coupled with a high swelling capacity. Moreover, it demonstrated potent antibacterial, antioxidant, and anti-inflammatory activities, promoting a favorable environment for wound healing. <i>In vitro</i> studies confirmed that our wound dressings effectively inhibited <i>Escherichia coli</i> (<i>E. coli</i>) and drug-resistant bacteria like <i>Klebsiella pneumoniae</i> (<i>K. pneumoniae</i>), <i>methicillin-resistant Staphylococcus aureus</i> (<i>MRSA</i>), and <i>methicillin-resistant coagulase-negative Staphylococcus</i> (<i>MR-CoNS</i>). Additionally, CA/HPCE had the potential to significantly augment fibroblast migration. Moreover, <i>in vivo</i> investigations confirmed that this system accelerated re-epithelialization, neovascularization, and collagen deposition while reducing inflammation. Immunohistochemistry (IHC) analysis of α-smooth muscle actin (α-SMA) indicated the absence of hypertrophic scar formation postdressing. These findings suggest that CA/HPCE is a highly effective and innovative solution for advanced wound care.