Abstract

Plant extracts have been widely used since ancient times for their many beneficial properties. Today, they are gaining renewed attention as a promising way to develop pharmaceutical products with a lower environmental impact and in alignment with circular economy framework. Therefore, we investigated the influence of some fruit peel aqueous extracts on a clinical condition that is still challenging to be treated, specifically, chronic wounds management. Plant aqueous extracts are reported to be rich in antioxidants, suggesting that their radi-cal scavenging activity would contribute to restoring the physiological conditions required for timely and com-plete wound closure. Indeed, excessive levels of reactive oxygen species often lead to oxidative stress, chronic inflammation, and fibrosis, resulting in a slowdown of the healing process and impaired tissue repair. In the pre-sent data set, Litchi chinensis (Sonn.) (Litchi, abbreviated as L), Acca sellowiana (O.Berg) (Feijoa, abbreviated as F) and Aesculus hippocastanum (L.) (horse chestnut, abbreviated as HC) peels were used as source of antioxi-dants. The extracts were tested to investigate different properties: DPPH (1,1-Diphenyl-2-picrylhydrazyl radical, 2,2-Diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl) assay was used to evaluate the antioxidant potential, cytotoxici-ty assay on WS1 human fibroblasts was performed through ptychographic quantitative phase imaging (QPI) and MTT [3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] assay to ensure safety, whilst wound healing assay on WS1 cells was conducted to verify the healing potential. L, F, and HC extracts demonstrated radical scavenging activity in the order of micrograms per mL and did not exhibit cytotoxicity at the tested con-ditions. Only L and F extracts promoted cell proliferation by decreasing the cell doubling time and a great heal-ing potential was shown by the HC extract. Considering their ability to modulate cellular processes fundamental to physiological wound healing, namely cell proliferation and migration, these extracts were incorporated into a topical formulation. Specifically, we formulated such extracts in film-casted silk fibroin (abbreviated as SF) patches to be applied on the injured skin. The silk fibroin–based patches retain clinically relevant features such as sufficient transparency for wound monitoring and a controlled biodegradation profile (80%, on average, bio-degradation gradually over 48 h), supporting their potential for advanced wound care applications. Once loaded with the extracts, the patches were investigated for their ability to release the antioxidant species, and for their biocompatibility on WS1 cells. The latter was assessed by multiple analysis: optical microscopy (cell morphology and adhesion to the patch), resazurin assay (metabolic activity of cells), phalloidin staining (cytoskeleton altera-tions). Silk-fibroin patches loaded with L and F extracts (SF-L and SF-F, respectively), but not that containing horse chestnut (SF-HC), were able to release antioxidant species at percentages that aligned with those of re-lated film employed in dermal applications. SF-HC and SF-L, but not SF-F, improved the metabolic activity of WS1 cells directly seeded on top of the patches, and all the tested patches provided contact guidance function-ality, which is required for effective integration between cells and scaffold. Overall, data highlight the promise of multifunctional biomaterials capable of simultaneously promoting tissue repair and supporting sustainability goals, paving the way for next-generation wound-care interventions with enhanced clinical and environmental value.