Comparative in vitro evaluation of elastogenic compounds for pharmacological modulation of extracellular matrix...

The balance of collagen and elastic fibers is crucial for skin structure, appearance, and function. As interest in skin regeneration and anti-aging grows, identifying compounds that stimulate elastogenesis remains a significant challenge. Many current treatments offer limited effectiveness, underscoring the need for advanced approaches in wound healing and regenerative medicine. Modulating extracellular matrix (ECM) production in dermal fibroblasts is a promising strategy for developing pharmacological therapies aimed at skin regeneration, wound healing, and anti-aging. In this study, a panel of pharmacologically active compounds was evaluated for their effects on primary human dermal fibroblasts. The tested compounds - retinoic acid (RA), dexamethasone (DXM), minoxidil sulfate (MNX), transforming growth factor beta 1 (TGF-β1), insulin-like growth factor 1 (IGF-1), copper sulfate (CuSO₄), dill extract (DE), magnesium ascorbyl phosphate (MAP, a stable vitamin C derivative), heparin (HEP), and γ-aminobutyric acid (GABA) - represent diverse biochemical classes and mechanisms of action. Pharmacological profiling enabled a comparative evaluation and ranking of compounds based on their ECM-modulating efficacy, viz. DXM, DE, IGF-1, HEP, RA, and TGF-β1 emerging as the most promising candidates. Moreover, scarring potential, safety, and cytotoxicity were evaluated in vitro. Notably, HEP, IGF-1, RA, and DXM also induced transient morphological changes in fibroblasts, which resolved at later time points. While these effects may reflect adaptive responses, potential long-term consequences cannot be excluded and need further investigation. These findings support further preclinical development of selected compounds as candidates for dermal therapeutics and skin regeneration strategies.