Modeling of Old Scars: Histopathological, Biochemical and Thermal Analysis of the Scar Tissue Maturation

SIMPLE SUMMARY: Severe skin scars (i.e., hypertrophic and keloid) induce physical and emotional discomfort and functional disorders such as contractures and body part deformations. Scar’s response to treatment depends on “maturity”, which increases with time but is not merely proportional to it. When “fresh”, scars are relatively more treatable by conservative methods, while the treatment is only partially efficient. In contrast, surgery is a preferred approach for the older scars, but it is associated with a risk of the scar regrowth and worsening after excision if unrecognized immature scar tissue remains in the operated lesion. Therefore, to develop better treatment and diagnostics of scars, understanding of the scar maturation is essential. This requires biologically accurate experimental models of skin scarring. The current models only mimic the early stages of skin scar development. They are useful for testing new scar-preventing approaches while not addressing the problem of the older scars that exist for years. In our study, we demonstrate a new rabbit model of “old” scars and explore what happens to the scar tissue during maturation. We define measurable signs to delineate the scar development stages and discuss how this knowledge can improve scar diagnostics and treatment. ABSTRACT: Mature hypertrophic scars (HSs) remain a challenging clinical problem, particularly due to the absence of biologically relevant experimental models as a standard rabbit ear HS model only reflects an early stage of scarring. The current study aims to adapt this animal model for simulation of mature HS by validating the time of the scar stabilization using qualitative and quantitative criteria. The full-thickness skin and perichondrium excision wounds were created on the ventral side of the rabbit ears. The tissue samples were studied on post-operation days (PODs) 30, 60, 90 and 120. The histopathological examination and morphometry were applied in parallel with biochemical analysis of protein and glycosaminoglycans (GAGs) content and amino acid composition. The supramolecular organization of collagen was explored by differential scanning calorimetry. Four stages of the rabbit ear HS maturation were delineated and attributed with the histolomorphometrical and physicochemical parameters of the tissue. The experimental scars formed in 30 days but stabilized structurally and biochemically only on POD 90–120. This evidence-based model can be used for the studies and testing of new treatments of the mature HSs.