Hypertrophic scars formed after burns remain a challenge in clinical practice. Development of effective scar therapies relies on validated animal models that mimic human hypertrophic scars. A consistent porcine full-thickness burn hypertrophic scar model has yet to be developed. We have previously reported that Shikonin induces apoptosis and reduces collagen production in hypertrophic scar fibroblasts in vitro and may therefore hold potential as a novel scar remediation therapy. In this study, we aimed to validate the potential of Shikonin on scar remediation in vivo. A novel porcine hypertrophic scar model was created after full-thickness burn wounds, and the effect of Shikonin on scar remediation was investigated. Clinical scar assessments, histology, and immunohistochemistry were used to evaluate scar appearance, morphology, and protein expression. Eight weeks after scar formation, clinical scar assessment indicated that the score of hypertrophic scars treated with Shikonin was significantly lower than that of the control group. Hypertrophic scars treated with Shikonin appeared flat, pink, and pliable. In addition, histological analysis indicated that hypertrophic scars treated with Shikonin exhibited reduced thickness of the epidermis and dermis, thin and even epithelial layers, reduced numbers of keratinocytes, uniform distribution of fibroblasts, and a parallel and loose arrangement of collagen fibers in the dermis. Moreover, immunohistochemical analysis indicated that Shikonin inhibited the expression of p63, cytokeratin 10, alpha-smooth muscle actin, transforming growth factor-beta 1, and collagen I, which play important roles in hypertrophic scar formation. Based on these results, we conclude that Shikonin has potential as a novel scar therapy.

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Scars are common complications of burns and trauma, resulting in mental trauma, physical pain, and a heavy financial burden for patients. Specific and effective anti‐scarring drugs are lacking in clinical practice. Phytochemicals are easily accessible, low in toxicity, and have various biological and pharmacological properties. Oxymatrine is a phytochemical that regulates autophagy networks. Autophagy is closely related to the maintenance, activity, differentiation, and life‐death of skin fibroblasts during wound repair, which results in pathological scars. We hypothesised that oxymatrine may promote hypertrophic scar repair by inhibiting fibroblast autophagy. In vitro studies showed that inhibition of autophagy by oxymatrine decreased viability and collagen metabolism, and increased apoptosis of human scar fibroblasts (HSFs). In vivo studies showed that inhibition of autophagy by oxymatrine promoted scar repair, resulting in a significantly improved final outcome of the hypertrophic scars, a smaller scar area, decreased epidermal and dermal thickness, and a significant downregulation of CK10, P63, collagen I, α‐SMA, and TGF‐β1. In summary, oxymatrine promoted hypertrophic scar repair by decreasing HSF viability and collagen, and inducing apoptosis via autophagy inhibition. This study provides a new perspective on the mechanism of hypertrophic burn scar formation, as well as key scientific data for the application of the phytochemical oxymatrine as a new method for the prevention and treatment of hypertrophic scars.

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