ArticleClinical, cosmetic and investigational dermatology2026
Temporal Pulse Structure of a 1550-nm Nonablative Fractional Laser Differentially Modulates Fibroblast Transcriptional Programs and Dermal Biomechanics.
Article in Clinical, cosmetic and investigational dermatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Purpose: Nonablative fractional laser (NAFL) therapy is a widely used energy-based device (EBD) modality for dermal remodeling and photorejuvenation. Pulse temporal structure-the combination of peak power and pulse duration at constant total fluence-represents an underexplored determinant of cellular response. Type-N (normal mode) and Type-T (thermal mode) pulse configurations of a 1550-nm NAFL system induce distinct pathway-level transcriptional responses in human dermal fibroblasts. The fibroblast subpopulation-level correlates and functional tissue consequences of these differences remain unknown. Methods: Bulk RNA sequencing (n = 3 per group) was performed on human dermal fibroblasts at three days post-irradiation. Transcriptome-wide correlation scores were calculated against four reference fibroblast subpopulation clusters: secretory-reticular (cluster 1), pro-inflammatory (cluster 2), secretory-papillary (cluster 3), and mesenchymal (cluster 9). Subpopulation marker gene expression and collagen family profiles were visualized using z-score-normalized heat maps. Bioprinted three-dimensional (3D) dermal constructs were irradiated in Type-N or Type-T mode under matched parameters and assessed by uniaxial compression testing on Day 8. Results: Control fibroblasts showed transcriptional resemblance to the secretory-reticular subpopulation, consistent with a stable homeostatic baseline. Type-N mode-irradiated fibroblasts showed a broad, non-specific transcriptional activation pattern with signals consistent with pro-inflammatory, mesenchymal, and secretory-reticular subpopulation programs, without a single dominant subpopulation tendency, accompanied by broad induction across all collagen structural classes and, most prominently, fibrillar collagens. Type-T mode-irradiated fibroblasts showed preferential transcriptional resemblance to the pro-inflammatory subpopulation, consistently supported across replicates and marker gene analysis, with overall attenuation of fibrillar collagen expression and selective enrichment of basement membrane-associated collagens. Type-N mode-irradiated constructs showed directionally higher compressive modulus than Type-T mode and controls. Conclusion: Pulse temporal structure is associated with distinct transcriptional tendencies in human dermal fibroblasts at equivalent total fluence. Type-T mode irradiation was associated with a robustly supported pro-inflammatory transcriptional tendency, while Type-N mode irradiation engaged a broad, non-specific activation pattern without preferential enrichment of a single subpopulation state. These molecular differences are directionally reflected in early biomechanical responses in the 3D dermal model and provide a framework for the mechanistic optimization of NAFL pulse parameters.
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