Regeneration in Aesthetic Medicine: Mechanisms, Evidence, and Clinical Boundaries.

BACKGROUND

Regeneration has emerged as a key concept in aesthetic medicine as the field evolves from predominantly volumetric correction toward biologically oriented strategies aimed at improving tissue quality, function, and long-term structural integrity. However, the widespread use of the term "regenerative" has often been used without biological precision, leading to conceptual overlap with repair, remodeling, and biostimulation. A critical evaluation of the biological basis and clinical evidence supporting regenerative claims is needed.

OBJECTIVE

To critically synthesize current biological, translational, and clinical evidence related to skin regeneration in aesthetic medicine, with emphasis on extracellular matrix remodeling, immune modulation, mechanotransduction, and dermal-hypodermal integration, and to contextualize the regenerative potential and limitations of commonly used biomaterials.

METHODS

A narrative review was conducted based on experimental studies, translational research, narrative and systematic reviews, and clinical investigations cited in the reference set. Evidence was qualitatively analyzed focusing on mechanisms of action, tissue-level interactions, immune responses, extracellular matrix dynamics, involvement of subcutaneous adipose compartments, and durability of clinical outcomes.

RESULTS

Cutaneous regeneration is a multilevel functional process driven by coordinated extracellular matrix reorganization, controlled inflammation, mechanotransduction, angiogenesis, and dermal-hypodermal crosstalk. Particulate collagen biostimulators (poly-l-lactic acid, poly-d,l-lactic acid, calcium hydroxyapatite, and polycaprolactone) demonstrate the most consistent evidence for sustained functional remodeling, with poly-l-lactic acid showing the strongest longitudinal and histological support. Hyaluronic acid-based fillers and skinboosters primarily act as microenvironmental modulators with limited regenerative depth. Polydioxanone threads induce localized mechanobiological remodeling that is highly technique dependent. Biological bioregenerators, including polynucleotides, polydeoxyribonucleotides, and extracellular vesicles, show strong mechanistic plausibility but limited and heterogeneous clinical evidence.

CONCLUSION

Regeneration in aesthetic medicine should be defined by biological mechanism, functional integration, and durability rather than by transient morphological change. A biologically accountable and evidence-based framework is essential for responsible clinical application.