Development of a Synergistic Nanomaterial Scaffold Combining Silver Nanoparticles, Collagen, and Doxycycline for Enhanced Scar-Free Skin Regeneration.

Introduction The efficacy of wound-healing treatments can be significantly enhanced through innovative combination therapies. This research investigates the wound-healing properties of a combination therapy involving silver nanoparticles (AgNPs) synthesized using Delphinium denudatum (Dd), bovine tendon collagen (BTC), and the antibiotic doxycycline (DOX) in Wistar albino rats. Each component has known therapeutic benefits: AgNPs possess antimicrobial properties, BTC aids in tissue regeneration, and DOX is an effective antibiotic. The synergy between these components is hypothesized to enhance wound closure, reduce inflammation, and promote scar-free healing. Methods The synthesis of DdAgNPs was carried out using Dd. The presence of AgNPs was confirmed by ultraviolet-visible (UV-Vis) spectroscopy and high-resolution transmission electron microscopy (HRTEM). The study was conducted on Wistar albino rats following ethical guidelines for animal research. The rats were divided into different groups to receive various treatments: DdAgNPs alone, BTC alone, DOX alone, combinations of two components, and the triple combination of DdAgNPs: BTC: DOX. Wound closure rates, epithelialization, and collagen deposition were monitored and recorded over time. Tissue samples from the wound sites were collected for histological analysis. Hematoxylin and eosin (H&E) staining was used to evaluate epithelialization and overall tissue architecture. Collagen deposition was assessed using Masson's trichrome staining. Additionally, the expression of cyclooxygenase-2 (COX-2) was measured as an indicator of inflammation. Results UV-Vis spectroscopy provided the characteristic surface plasmon resonance peak indicative of AgNPs, while HRTEM revealed the morphology and size of the nanoparticles, showing spherical particles with an average size of 35±10.42 nm. The combination therapy of DdAgNPs: BTC: DOX significantly enhanced wound closure compared to individual and dual-component treatments. This was evidenced by faster epithelialization and increased collagen deposition. The histological analysis showed that the triple combination treatment resulted in more organized tissue architecture and denser collagen fibers. Furthermore, the treatment led to a marked decrease in COX-2 expression, indicating reduced inflammation and potential for lower scar formation. Conclusion The synergistic application of DdAgNPs, BTC, and DOX presents a promising strategy for advanced wound healing and tissue regeneration. The combination therapy not only accelerates wound closure but also enhances the quality of healing by promoting epithelialization and collagen deposition while reducing inflammation. These findings offer a potential pathway for developing effective, scar-free healing solutions, highlighting the benefits of integrating multiple therapeutic agents in wound care.