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Background: Skin grafting is a helpful instrument in a plastic surgeon's arsenal. Several types of dressings were designed to facilitate the process of graft integration. Negative-pressure wound therapy is a proven dressing method, enhancing graft survival through several mechanisms: aspiration of secretions, stimulation of neoangiogenesis, and promotion of an anti-inflammatory environment. Silver nanoparticle dressings also bring multiple benefits by bearing an antimicrobial effect and providing a humid medium, which are favorable for epithelialization. The combination of NPWT (negative-pressure wound therapy) with AgNPs (silver nanoparticles) has not been widely studied. Materials and methods: This study aimed to compare the outcomes of silver nanoparticle sheets with the combination of negative-pressure wound therapy and silver nanoparticle dressings. We conducted a comparative prospective study on 80 patients admitted to the Plastic Surgery Department of "Prof. Dr. Agrippa Ionescu" Emergency Clinical Hospital between 1st of January 2020 and 31st of December 2022. The study population was randomized to receive either silver nanoparticle dressings or negative-pressure wound therapy (NPWT) combined with silver nanoparticle dressings. Various parameters were monitored, including patient comorbidities and graft-related data such as defect etiology, graft integration, and graft size. Dressings were changed, and graft status was evaluated at 7, 10, and 14 days postoperatively. Additionally, baseline C-reactive protein (CRP) levels were measured before surgery and 7, 10, and 14 days postoperatively. Results: The study demonstrated an enhanced integration of skin grafts at all evaluation stages when employing NPWT combined with AgNPs, particularly evident 10 days post operation. Significant variations in graft integration were also observed based on factors such as diabetes, cardiovascular disease, graft size, or the origin of the grafted defect. Moreover, dynamic C-reactive protein monitoring showed a statistically significant decrease in CRP levels 10 days post operation among patients treated with NPWT in conjunction with silver dressing, consistent with the nearly complete integration of skin grafts at this evaluation threshold. Conclusion: Several factors influence the postoperative evolution of split-skin grafts. Postoperative dressings target local factors to enhance graft integration further. Our research demonstrated that the innovative combination of NPWT-assisted dressings, complemented by a silver nanoparticle sheet, resulted in improved benefits for graft integration and the alleviation of systemic inflammation. [ABSTRACT FROM AUTHOR]