Topical application of a film‐forming emulgel dressing that controls the release of stratifin and acetylsalicylic acid and improves/prevents hypertrophic scarring

Abstract

Here, we evaluate the efficacy of an emulgel dressing to control the release of an antifibrogenic factor, stratifin (SFN), along with an anti-inflammatory drug, acetylsalicylic acid (ASA), to be used as a wound dressing with hypertrophic scar reducing features. Emulgel dressings were prepared by dispersing positively charged submicron vesicles in carboxymethyl cellulose gel. Release kinetics of SFN/ASA and toxicity for primary skin cells were assessed in vitro. Antifibrogenic efficacy of medicated emulgel dressings was tested on a rabbit ear fibrotic model. Following topical application on the wounds, emulgels formed an occlusive film and controlled the release of SFN and ASA for 7 and 24 hours, respectively. Wounds treated with SFN/ASA-containing emulgel dressings showed an 80% reduction in scar elevation compared with untreated controls. Topical formulations were nontoxic for cultured human keratinocytes and fibroblasts. Inflammation was significantly controlled in treated wounds, as shown by a reduced number of infiltrated CD3(+) T cells (p < 0.001) and macrophages. SFN/ASA-treated wounds showed a significantly higher (p < 0.001) expression of matrix metalloproteinase-1, resulting in reduced collagen deposition and less scarring. Film-forming emulgel dressings that control the release of antifibrogenic and anti-inflammatory factors provide an excellent treatment option for postburn hypertrophic scar management.

AnIn-SituForming Skin Substitute Improves Healing Outcome in a Hypertrophic Scar Model

“…As a standard model of scar hypertrophy, four New Zealand white rabbits (*3 kg) were used to investigate the utility of the in-situ forming scaffolds to be employed as skin substitutes as previously published. 2,[24][25][26] Animals were anesthetized using ketamine/xylazine induction and isoflourene maintenance. Meloxicam (0.3 mg/Kg) prophylaxis was used as an analgesic.…”

“…Healing outcome -scar elevation index, epidermal thickness, and cellularity Quality of wound healing can be measured in a number of ways, three of which are the scar elevation index (SEI), epidermal thickness (ET), and cellularity. 2,[24][25][26] The SEI can easily be calculated using a formula (1) and it is a measure of the ratio in ET and dermal thickness (DT) of the wounded area to that of the adjacent normal skin. DT and ET are secondary markers of scarring and are calculated as the average pixel thickness across the neo-tissue.…”

“…To determine the abundance of collagen deposition, paraffin-embedded sections were de-waxed and stained for collagen with Masson's Trichrome as previously described. 25 Keratin and muscle fibers are stained red, collagen fibers are stained blue, and cell cytoplasm and nuclei are stained light pink and dark brown. Total RNA was extracted from scar tissue using Trizol reagent according to the manufacturer's instructions (Invitrogen).…”

Prostaglandin E2 inhibits collagen synthesis in dermal fibroblasts and prevents hypertrophic scar formation in vivo

“…All measurements were taken within the confines of the wounded area, and the epithelial height was excluded from the SEI calculations. For the epithelial parameter, the epidermal thickness index (ETI) was used to evaluate the degree of epidermal hypertrophy, which was calculated as the ratio of the averaged epidermal height in scar tissue to the averaged epidermal height in adjacent normal skin (26).…”

Bilaminar Device of Poly(Lactic‐co‐Glycolic Acid)/Collagen Cultured With Adipose‐Derived Stem Cells for Dermal Regeneration

“…Myofibroblasts are cells characterized by the expression of alpha-smooth muscle actin (α-SMA) with a contractile phenotype and related to fibrosis formation (18). Drugs with antiscarring effect reduce the conversion of fibroblasts to myofibroblasts and promote a balance between the synthesis and degradation of collagen which reduces the formation of fibrosis (19,20).…”