Non-healing chronic wounds are severe complications, which can often eventually lead to amputations. As such, there is a clear clinical need for dressings that promote the healing of chronic wounds. An advanced wound dressing aims to keep wound tissues moist while offering increased healing rates, preventing scar formation, reducing pain, minimizing infection, improving cosmetics, and lowering overall health care costs. We have previously developed tetrameric peptides Ac-IVZK-NH 2 (Ac-Ile-Val-Cha-Lys-NH 2 ) and Ac-IVFK-NH 2 (Ac-Ile-Val-Phe-Lys-NH 2 ) that self-assemble into nanofibrous hydrogels with biomimetic properties resembling those of collagen. In our study, we tested if these nanogels can fulfill the wound healing criteria mentioned above, and found that the nanogels are suitable scaffolds for encapsulating human dermal fibroblasts. We selected peptide nanogels Ac-IVZK-NH 2 and Ac-IVFK-NH 2 and produced silver nanoparticles in situ within the nanogels to assess their efficacy on micropigs with full-thickness excision wounds. The in situ generation of the silver nanoparticles was done solely through UV irradiation, no reducing agent was used. Application of the peptide nanogels on full thickness micropig wounds demonstrated that the scaffolds are biocompatible and did not trigger wound inflammation. This suggests that the scaffolds are safe for topical application. A comparison of the effect of both nanogels-even without the addition of the silver nanoparticles, revealed that the scaffold itself has a high potential to act as an antibacterial agent, which may suppress both the inflammatory reaction and the activity of proteases. Interestingly, the effect on wound closure of the peptide nanogels was comparable to those of standard care hydrogels. Despite our promising results, there is still much to learn about the molecular basis underlying the efficacy of tetrameric peptide nanogels in wound healing. This will support the urgent demand for advanced treatments of diabetic wounds, based on scientifically and clinically validated studies.
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