Development of a Porcine Full-Thickness Burn Hypertrophic Scar Model and Investigation of the Effects of Shikonin on Hypertrophic Scar Remediation

Abstract

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.

Animal Models of Burn Wound Management

“…This model of hypertrophic scarring after deep dermal partial-thickness burn injury can be used to further understand the pathophysiology of burn wound healing and scar formation as well as for the testing of various agents which could potentially improve the outcome of the burn wound. Another report demonstrated the reproducible burn hypertrophic scar model using the Bama miniature pig by applying a homemade heating device for 35 seconds followed by debridement surgery [45]. This model has displayed a similar macroscopic, histologic, and biologic criteria of burn wound compared to the human hypertrophic scars.…”

Adipose-Derived Mesenchymal Stromal Cells in Regenerative Medicine: State of Play, Current Clinical Trials, and Future Prospects

“…180,181 Both therapies also led to an increase in angiogenic markers coupled with a decrease in fibrotic markers such as TGF-b1. [182][183][184] Rapp et al compared these two kinds of products in a porcine model of hypertrophic scar after burning. They reported very similar results, that is, a rapid reduction of erythema and a decrease in scar thickness.…”

Comparison of hypertrophic scarring on a red Duroc pig and a Guangxi Mini Bama pig

“…10 Naturally, the Mini Bama pig, characterised by its small size, slow growth, good genetic stability and minor individual differences, has been proposed as a replacement for the red Duroc pig. 11 Studies have also shown that skin stratification, thickness and structure of the Mini Bama pig are similar to those of human skin. Recently, Deng et al 11 created a full-thickness dermal burn injury on the Guangxi Bama minipig that resulted in hypertrophic scars.…”

“…11 Studies have also shown that skin stratification, thickness and structure of the Mini Bama pig are similar to those of human skin. Recently, Deng et al 11 created a full-thickness dermal burn injury on the Guangxi Bama minipig that resulted in hypertrophic scars. Using this model, they confirmed the anti-scar effect of Shikonin, an active component extracted from Radix Arnebiae that has been studied to induce apoptosis and reduce the production of collagen in hypertrophic scar-derived fibroblasts.…”