The Pathophysiology and Management of Pathologic Scarring—a Contemporary Review

Significance: Pathologic scarring occurs secondary to imbalances in the cellular mechanisms of wound healing and affects millions of people annually. This review article aims to provide a concise overview of the pathophysiology and management of pathologic scarring for clinicians and scientists alike. Recent Advances: Contemporary research in the field has identified aberrations in transforming growth factor-β/small mothers against decapentaplegic (TGF-β/SMAD) signaling pathways as key drivers of pathologic scar formation; indeed, this pathway is targeted by many treatment modalities and translational investigations currently underway. Although intralesional injection of corticosteroids has been the gold standard in the treatment of pathologic scarring, studies show greater treatment efficacy with the use of combination injections such as triamcinolone/5-fluorouracil and triamcinolone/botulinum toxin. Adjunctive therapies including ablative fractional carbon dioxide/erbium-doped yttrium aluminum garnet and non-ablative pulsed-dye lasers, microneedling, and carboxytherapy have shown encouraging results in small cohort studies. Translational investigations involving the use of nanogels, RNA interference, and small molecules targeting TGF-β/SMAD pathways are also currently underway and hold promise for the future. Critical Issues: The heterogeneous nature of hypertrophic scars and keloids poses significant challenges in formulating standardized treatment and assessment protocols, thereby limiting the conclusions that can be drawn. Future Directions: Rigorous clinical trials into the individual and synergistic effects of these therapies would be ideal before any definitive conclusions or evidence-based treatment recommendations can be made. Owing to the heterogeneity of the pathology and patient population, well-conducted cohort studies may be the next best option.