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

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.

Local Delivery of Pirfenidone by PLA Implants Modifies Foreign Body Reaction and Prevents Fibrosis

“…Finally, we revealed a very sensitive measure of the maturation of connective tissue structures using the DSC analysis of the thermal stability of collagen in the peri-implant tissue samples. The obtained observations corroborate with our previous interpretations and conclusions that were done in a scar-modelling experiment on rabbit ears [ 60 ]. Briefly, the thermostability of collagen was dependent on amount of covalent cross-links, the interaction of collagen molecules and structural integrity of collagen network.…”

“…In the present study, we explored the effects of a new experimental IDDS prototype for the local delivery of PF on FBR and PIF in an ear skin pocket model in rabbits. The animal model used in this work represents a modification of the approach used for the simulation of excessive (hypertrophic) scarring that relies on the ischemic nature of the rabbit ear skin wounds [ 59 , 60 ]. The implants were surgically fixed between skin derma and cartilage plate.…”

“…In this study, we aimed to explore the effects of the PF-loaded slowly-biodegradable PLA implants (PLA@PF) acting as a prototype IDDS on FBR and PIF in a rabbit ear skin pocket model. The full-thickness excision skin wounds on the ventral side of the rabbit ears are intrinsically ischemic and conventionally used for modeling of scarring [ 59 , 60 ]. We slightly modified the excision models to secure precise implants’ positions, while preserving the pro-fibrotic environment around them.…”

Down-Regulating Scar Formation by Microneedles Directly via a Mechanical Communication Pathway

“…Generally, a hypertrophic scar is nonuniform in thickness, usually ranging from 0.5 to 2 mm in the rabbit ear HS model. 39 , 40 The needles with a length of 500, 1000, and 1500 μm were fabricated to evaluate the length effects of MNs ( Figure S2A ). As shown in Figure S2B , the 500 μm MN was too short to achieve an efficient penetration.…”

Automated Structural Analysis and Quantitative Characterization of Scar Tissue Using Machine Learning

“…The limited field of view often restricts analysis of the entire scar lesion in the whole slide image (WSI). For instance, recent research studies have simply manually located scar lesions to analyze a region of interest (ROI) in the scar area [ 6 , 7 ]. An in-depth analysis of a scar region is also difficult, owing to the comparable color distributions in hematoxylin and eosin (HE)-stained images.…”