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Current treatment for chronic infectious wounds is limited due to severe drug resistance in certain bacteria. Therefore, the development of new composite hydrogels with nonantibiotic antibacterial and pro-wound repair is important. Here, we present a photothermal antibacterial composite hydrogel fabricated with a coating of Fe 2+ cross-linked carboxymethyl chitosan (FeCMCS) following the incorporation of melanin nanoparticles (MNPs) and the Cy RL-QN15 peptide. Various physical and photothermal properties of the hydrogel were characterized. Cell proliferation, migration, cycle, and free-radical scavenging activity were assessed, and the antimicrobial properties of the hydrogel were probed by photothermal therapy. The effects of the hydrogel were validated in a model of methicillin-resistant Staphylococcus aureus (MRSA) infection with full-thickness injury. This effect was further confirmed by changes in cytokines associated with inflammation, re-epithelialization, and angiogenesis on the seventh day after wound formation. The MNPs demonstrated robust photothermal conversion capabilities. The composite hydrogel (MNPs/Cy RL-QN15 /FeCMCS) promoted keratinocyte and fibroblast proliferation and migration while exhibiting high antibacterial efficacy, effectively killing more than 95% of Gram-positive and Gram-negative bacteria. In vivo study using an MRSA-infected full-thickness injury model demonstrated good therapeutic efficacy of the hydrogel in promoting regeneration and remodeling of chronically infected wounds by alleviating inflammatory response and accelerating re-epithelialization and collagen deposition. The MNPs/Cy RL-QN15 /FeCMCS hydrogel showed excellent antibacterial and prohealing effects on infected wounds, indicating potential as a promising candidate for wound healing promotion.

Chronic and non-healing wounds pose a great challenge to clinical management and patients. Many studies have explored novel interventions against skin wounds, with bioactive peptides, nanoparticles, and hydrogels arousing considerable attention regarding their therapeutic potential. In this study, the prohealing peptide RL-QN15 was loaded into hollow silica nanoparticles (HSNs), with these HSN@RL-QN15 nanocomposites then combined with zinc alginate (ZA) gels to obtain HSN@RL-QN15/ZA hydrogel. The characteristics, biological properties, and safety profiles of the hydrogel composites were then evaluated. Results showed that the hydrogel had good porosity, hemocompatibility, biocompatibility, and broad-spectrum antimicrobial activity, with the slow release of loaded RL-QN15. Further analysis indicated that the hydrogel promoted skin cell proliferation and keratinocyte scratch repair, regulated angiogenesis, reduced inflammation, and accelerated re-epithelialization and granulation tissue formation, resulting in the rapid healing of both full-thickness skin wounds and methicillin-resistant Staphylococcus aureus biofilm-infected chronic wounds in mice. This peptide-based hydrogel provides a novel intervention for the treatment of chronic skin wounds and shows promise as a wound dressing in the field of tissue regeneration.

Background: Skin wound healing remains a considerable clinical challenge, thus stressing the urgent need for the development of new interventions to promote repair. Recent researches indicate that both peptides and nanoparticles may be potential therapies for the treatment of skin wounds., Methods: In the current study, the mesoporous polydopamine (MPDA) nanoparticles were prepared and the peptide RL-QN15 that was previously identified from amphibian skin secretions and exhibited significant potential as a novel prohealing agent was successfully loaded onto the MPDA nanoparticles, which was confirmed by results of analysis of scanning electron microscopy and fourier transform infrared spectroscopy. The encapsulation efficiency and sustained release rate of RL-QN15 from the nanocomposites were determined. The prohealing potency of nanocomposites were evaluated by full-thickness injured wounds in both mice and swine and burn wounds in mice., Results: Our results indicated that, compared with RL-QN15 alone, the prohealing potency of nanocomposites of MPDA and RL-QN15 in the full-thickness injured wounds and burn wounds in mice was increased by up to 50 times through the slow release of RL-QN15. Moreover, the load on the MPDA obviously increased the prohealing activities of RL-QN15 in full-thickness injured wounds in swine. In addition, the obvious increase in the prohealing potency of nanocomposites of MPDA and RL-QN15 was also proved by the results from histological analysis., Conclusions: Based on our knowledge, this is the first research to report that the load of MPDA nanoparticles could significantly increase the prohealing potency of peptide and hence highlighted the promising potential of MPDA nanoparticles-carrying peptide RL-QN15 for skin wound therapy., (© 2021. The Author(s).)

Background: Although the treatments of skin wounds have greatly improved with the increase in therapeutic methods and agents, available interventions still cannot meet the current clinical needs. Therefore, the development of new pro-regenerative therapies remains urgent. Owing to their unique characteristics, both nanomaterials and peptides have provided novel clues for the development of pro-regenerative agents, however, more efforts were still be awaited and anticipated., Results: In the current research, Hollow polydopamine (HPDA) nanoparticles were synthesized and HPDA nanoparticles loading with RL-QN15 (HPDAlR) that was an amphibian-derived peptide with obvious prohealing activities were prepared successfully. The characterization, biodistribution and clearance of both HPDA nanoparticles and HPDAlR were evaluated, the loading efficiency of HPDA against RL-QN15 and the slow-releasing rate of RL-QN15 from HPDAlR were also determined. Our results showed that both HPDA nanoparticles and HPDAlR exerted no obvious toxicity against keratinocyte, macrophage and mice, and HPDA nanoparticles showed no prohealing potency in vivo and in vitro. Interestingly, HPDAlR significantly enhanced the ability of RL-QN15 to accelerate the healing of scratch of keratinocytes and selectively modulate the release of healing-involved cytokines from macrophages. More importantly, in comparison with RL-QN15, by evaluating on animal models of full-thickness injured skin wounds in mice and oral ulcers in rats, HPDAlR showed significant increasing in the pro-regenerative potency of 50 and 10 times, respectively. Moreover, HPDAlR also enhanced the prohealing efficiency of peptide RL-QN15 against skin scald in mice and full-thickness injured wounds in swine., Conclusions: HPDA obviously enhanced the pro-regenerative potency of RL-QN15 in vitro and in vivo, hence HPDAlR exhibited great potential in the development of therapeutics for skin wound healing., (© 2021. The Author(s).)