The objective of this work is to analyze modern pharmacological approaches to the prevention of pathological scarring and to characterize antifibrotic and anti-inflammatory agents that influence the key biochemical mechanisms of fibrogenesis.
Pathological scarring remains one of the most pressing challenges in modern plastic and reconstructive surgery, as hypertrophic scars and keloids can significantly compromise the aesthetic outcome of surgical interventions and negatively affect the functional state of tissues [1, p. 4674; 9, p. 3–4]. The formation of a pathological scar is associated with an imbalance between the synthesis and degradation of extracellular matrix (ECM) components, fibroblast hyperactivation, prolonged inflammation, and dysregulation of the TGF-β/Smad signaling pathway [1, p. 4674; 4, pp. 6–7]. Under normal conditions, the healing process proceeds through phases of inflammation, proliferation, and remodeling; however, disruption of these stages leads to excessive activation of myofibroblasts [3, pp. 5–8]. These cells intensively synthesize type I and III collagen, fibronectin, and other structural proteins, causing tissue induration and the formation of pathological scar mass [1, p. 4674].
A significant role is also played by the decreased activity of matrix metalloproteinases (MMPs) and increased levels of their tissue inhibitors (TIMPs), which hinders normal collagen degradation [3, pp. 6–7]. Fibrosis exacerbation is promoted by chronic inflammation: cytokines IL-1β, IL-6, TNF-α, and reactive oxygen species (ROS) activate TGF-β-dependent pathways, enhancing fibroblast proliferation and contributing to the formation of a dense scar matrix [3, pp. 5–8; 7, pp. 333–335]. Consequently, pharmacological prevention of pathological scarring represents a crucial area of modern biochemistry and clinical pharmacology.
Antifibrotic agents represent one of the most promising directions in current research. Pirfenidone, known as a treatment for idiopathic pulmonary fibrosis, demonstrates a significant ability to inhibit TGF-β1 expression and the Smad-2/3 signaling cascade, reduce collagen synthesis, limit fibroblast-to-myofibroblast differentiation, and decrease α-SMA expression [2, pp. 82–84; 4, pp. 6–7]. Experimental data indicate pirfenidone’s capacity to reduce scar tissue thickness and improve collagen fiber structure [2, pp. 85–86]. Topical formulations of pirfenidone, particularly gels and creams, show high potential due to minimal systemic toxicity and the possibility of targeted action directly within the postoperative wound zone [2, pp. 86–88].
Statins, despite their traditional application in cardiology, also exhibit significant antifibrotic activity. Their mechanism involves the inhibition of the Rho/ROCK signaling pathway, which participates in myofibroblast differentiation, as well as the reduction of connective tissue growth factor (CTGF) synthesis — a key mediator of fibrogenesis [5, pp. 3004–3006]. In vitro studies show that simvastatin attenuates TGF-β-induced collagen synthesis and downregulates fibrosis-related gene expression, providing a rationale for the further development of topical statin formulations in dermatology and plastic surgery [5, pp. 3006–3008].
Retinoids, specifically tretinoin and isotretinoin, possess the ability to modulate fibroblast differentiation, reduce collagen synthesis, and increase MMP activity [6, pp. NP358–NP360]. Biochemically, retinoids promote the normalization of the balance between ECM synthesis and degradation, making them beneficial for the prevention of hypertrophic scars, particularly following superficial plastic surgeries [6, pp. NP360–NP362].
The group of innovative agents includes TGF-β inhibitors, Smad modulators, angiotensin II antagonists (e.g., losartan), lysyl oxidase inhibitors, and galectin-3 inhibitors. These agents demonstrate high antifibrotic potential in preclinical models, although their clinical application remains limited at present [4, pp. 8–10].
Anti-inflammatory agents play a vital role in the early phase of scar formation. Non-steroidal anti-inflammatory drugs (NSAIDs) lower the levels of prostaglandins and pro-inflammatory cytokines, thereby reducing fibroblast activation [7, pp. 332–334]. Corticosteroids, particularly triamcinolone, are effective in treating established keloids; however, their prophylactic use is limited due to the risk of tissue atrophy and pigmentation changes [7, pp. 335–337]. Melatonin exhibits antioxidant and anti-inflammatory properties, suppresses TGF-β-dependent reactions, and may potentially potentiate the effects of antifibrotic therapy [3, pp. 8–9].
The most promising direction is considered to be the application of combined approaches. Strategies that combine pharmacological agents with physical modalities, such as compression, silicone gels, laser remodeling, and phototherapy, have proven effective [9, p. 4]. Drug delivery technologies are developing intensively, specifically nanoparticles, liposomes, and polymer matrices, which ensure prolonged, localized release of antifibrotic agents in the surgical wound area [8, pp. 118–121].
Thus, the pharmacological prevention of pathological scarring is based on targeted action on the key links of fibrogenesis and inflammation. Antifibrotic agents, particularly pirfenidone, statins, and retinoids, demonstrate significant potential for clinical application. Anti-inflammatory drugs potentiate their action by reducing fibroblast activation and oxidative stress. The combination of various methods yields the best results and forms the basis of modern approaches to preventing pathological scars in plastic surgery. Further research should focus on the development of highly selective topical preparations and delivery technologies capable of minimizing fibrosis risks and ensuring optimal surgical outcomes.
Список літератури:
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2. Saito A. Pirfenidone in fibrosis treatment: molecular mechanisms and clinical perspectives // Journal of Dermatological Science. 2021. Vol. 104, no. 2. P. 80–88.
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