## 4 Conclusions  
The demand for the sustainable production of therapeutics is increasing. The biosynthesis of nanoparticles is an opportunity to use upcycled industrial waste since plants are rich in terpenoids, alkaloids, and phenolics, and any of these molecules can be used for the synthesis. This type of synthesis can also overcome the toxicity associated with chemical synthesis. Biogenic silver nanoparticles have interesting pharmacological features that look promising for the topical treatment of skin diseases. The unique chemical composition of the plant extract affects the characteristics and properties of the AgNP. To the best of our knowledge, this is the first report on the use of a green-tomato-derived extract obtained by subcritical water treatment for the biosynthesis of metallic nanoparticles. This subcritical water extraction process preserved the phenolic content of the green tomato extract. The pre-formulation studies elucidated the role of the main parameters involved in the biosynthesis of AgNP, namely, pH, silver nitrate concentration, time, and temperature. AgNP formation can be confirmed by a color change and by the SPR band in the UV-vis absorption spectrum. The AgNP produced had the proper size, a reasonable polydispersity index, and good stability, confirmed by the value of its zeta potential. AFM and TEM confirmed that AgNP had a spherical-like shape, and the size distribution was homogeneous. The size obtained by these methods can be considered suitable for topical administration [55]. In vitro assays confirmed the cytocompatible nature of the AgNP toward human cells. Further studies are needed to assess the internalization and elimination profiles of AgNP to accurately estimate the potential adverse effects associated with their interaction with human cells. In vitro antimicrobial activity showed the susceptibility of Gram(\(-\)) bacteria to biogenic AgNP. The ex vivo antimicrobial assay reinforces the safety of AgNP after topical application. The in vivo assay demonstrated good wound-healing properties, comparable to commercial silver-based topical formulations. Considering all of the results, this study demonstrated the potential of industrial waste (green tomatoes) to be used in a green approach to the biosynthesis of AgNP under simple and eco-friendly conditions. The developed AgNP were revealed to have antimicrobial and wound-healing properties with an adequate profile for future biomedical applications.  
Conceptualization, M.C. and S.S.; methodology, D.C.; software, C.F.-S.; validation, L.A., F.A.C. and P.S.; formal analysis, D.C.; investigation, M.C. and S.S.; resources, M.C. and S.S.; writing--original draft preparation, D.C.; writing--review and editing, D.C., C.F.-S., F.A.C., L.A., P.S., M.C. and S.S.; supervision, M.C. and S.S. All authors have read and agreed to the published version of the manuscript.  
The authors acknowledge Fundacao para a Ciencia e a Tecnologia (FCT) through projects UIDB/04138/2020, UIDP/04138/2020, LA/P/0008/2020, UIDP/50006/2020, and UIDB/50006/2020. They also acknowledge financial support to CESAM by FCT/MCTES (UIDP/50017/2020 + UIDB/50017/2020 + LA/P/0094/2020).  
The raw data supporting the conclusions of this article will be made available by the authors on request.  
The authors declare no conflicts of interest.  
Figure 10: Representative images of histological sections of incisional wounds after 7 days of administration. (**A**) Placebo gel; (**B**) Silvederna® cream; (**C**) AgNP formulation. Scale bars = 200 μm.