A marine-derived collagen-based skin substitute for skin regeneration: a preliminary study

Skin wounds are a challenging problem in the medical field and an economical burden. Skin substitutes (SS) are a promising alternative for skin wound healing since they mimic the natural skin structure and support its regeneration. Here, we present preliminary results about the application of an innovative marine-derived collagen-based SS in a secondary intention wound healing model. METHODS: The collagen used to produce the SS was obtained from sea urchin (Paracentrotus lividus) food industry wastes, extracted in its fully native fibrillar and GAG-decorated form [1]. Two wounds (4x4 cm) were surgically induced on the back of three sheep: one of them was treated with the SS and one left untreated (placebo). Clinical evaluations for wound contraction and re-epithelialization were performed every week. At 7, 14, 21 and 42 days, biopsies were collected with a 6 mm2 punch in order to perform histopathological (H&E) and molecular (qPCR) analyses. Histological analyses allowed to provide a score to the maturation of granulation tissue (GT) and skin adnexa. Gene expression analysis was performed for Collagen1, Collagen3, VEGF and hair-keratin (hKER). RESULTS: Clinically, the SS led to a better re-epithelialization than the placebo while no differences in wound contraction were observed. Treated wounds showed a faster histological resolution of GT at 21 days, with no exuberant deposition of scarring tissue at 42 days; this result was further corroborated by the different expression levels of both collagen types at 14 and 21 days. Concomitantly, the higher expression of VEGF (day 14) was detected. In untreated wounds, on the contrary, GT appeared only at 14 days and did not mature properly leading to dermal fibrosis at 42 days. SS application led to the development of a larger amount and better developed skin adnexa (present since day 14) than untreated wounds: treated wounds started to express hKER since day 14. DISCUSSION & CONCLUSIONS: At 42 days, a faster re-epithelialization, a better development of skin adnexa and a properly deposition of GT were observed in the SS-treated wounds while the untreated ones showed a hypertrophic epidermis and fibrosis, indicators of a tissue still in the process of healing. Interestingly, VEGF expression might have supported GT maturation. Therefore, our preliminary findings suggest an overall better skin repair of the SS treatment than the placebo. Future studies should compare these beneficial effects with a commercially available SS (Integra®). REFERENCES: [1] Ferrario et al. Mar Environ Res. Jul;128:46-57, 2017