Repositioning Non‐Ablative Fractional Lasers ‐ Molecular and Histological Insights from a scoping review

Near-infrared non-ablative fractional lasers (NAFL) are established for skin rejuvenation and scar treatment and have attracted interest for their expanding therapeutic potential. This scoping review aims to revisit and reposition NAFL within a fluence-dependent continuum of tissue modulation, based on evidence from 27 studies of lasers operating at 1540-1570 nanometers, comprising ten molecular biology studies and 17 histological analyses. Histological data demonstrated a fluence-dependent tissue response: lower fluences preserved the stratum corneum, whereas higher fluences produced marked epidermal damage with subepidermal clefting, indicating a semi-ablative pattern. Both histological and molecular findings supported parallel spatiotemporal remodeling cascade, consisting of an initial inflammatory phase dominated by neutrophil infiltration and upregulation of heat shock proteins, interleukins, and matrix metalloproteinases; followed by a proliferative phase within 24 hours, characterized by keratinocyte bridging, re-epithelialization, and increased mitochondrial activity; and culminate in a prolonged remodeling phase (weeks 2-12), marked by collagen and elastin fibers synthesis and reorganization. By integrating evidence from molecular and histological studies, this review repositions NAFL within a fluence-dependent continuum of tissue modulation, ranging from non-ablative photothermal interactions to progressively barrier-disruptive treatment modalities. This framework holds perspectives for broadening the clinical scope, particularly for applications in laser-assisted drug delivery and skin cancer prevention.