Laser-Induced Optical Breakdown for Melasma and Photoaging: Molecular Mechanisms, Optical Biopsy Assessment, and Emerging Nanozyme-Based Adjuncts; A Systematic Review

Background: Picosecond laser-induced optical breakdown (LIOB), particularly when generated using a diffractive lens array, creates spatially confined photomechanical microinjury with limited nonspecific thermal damage. This review evaluates the role of LIOB in melasma and photoaging, with emphasis on the distinction between pigment fragmentation and regenerative tissue re-sponses. Preclinical and translational studies indicate that LIOB may promote extracellular matrix remodeling through TGF-β/Smad signaling while attenuating matrix-degrading and inflamma-tory pathways, including MMP-9 and NF-κB. Cellular-resolution full-field optical coherence to-mography (CRFF-OCT), coupled with computer-aided image analysis, offers a non-invasive ap-proach for longitudinal assessment of melanin morphology, the dermal–epidermal junction, col-lagen architecture, and treatment-related structural change. Hyperbranched polymer dots (HPDs) are additionally considered as experimental nanozyme-based adjuncts because of their antioxidant and regenerative properties; however, their relevance to melasma remains preclinical. Collec-tively, LIOB, quantitative optical biopsy, and bioactive nanomaterials provide a conceptual preci-sion-medicine framework for treating melasma as a chronic photoaging-associated disorder, alt-hough further prospective validation is required before these components can be integrated into routine care. Objectives: To critically synthesize the available clinical and preclinical evidence on LIOB for melasma and photoaging, evaluate CRFF-OCT as a potential tool for structural assess-ment and treatment monitoring, and describe the current translational evidence for HPDs as ex-perimental adjuncts. Methods: A structured literature search was conducted using PubMed, Sco-pus, ScienceDirect, and Google Scholar, supplemented by manual screening of reference lists. The principal search period covered January 2015 to May 2026, with earlier landmark publications considered when relevant. Eligible publications addressed the clinical applications, biological mechanisms, imaging assessment, or potential adjunctive approaches related to picosecond LIOB, melasma, photoaging, and skin remodeling. Clinical, translational, and experimental evidence was considered. Findings were synthesized qualitatively because of the heterogeneity of the in-cluded evidence, and no meta-analysis was performed. The last search date for this study was February 23, 2026. Results: A total of 37 studies are included in this review, and they emcompass experimental studies, cohorts, and literature reviews. Available data suggests that LIOB may promote extracellular matrix remodeling through transforming growth factor-β (TGF-β)/Smad signaling while modulating matrix-degrading and inflammatory pathways, including matrix metalloproteinase-9 (MMP-9) and nuclear factor kappa B (NF-κB), which are key pathways to treating melasma and photoaging. Computer aided optical confluence tomography, combined with computer-aided image analysis, offers a noninvasive approach for longitudinal assessment of melanin morphology, the dermal–epidermal junction, collagen architecture, and treatment-related structural changes. Hyperbranched polymer dots (HPDs) demonstrate experimental antioxidant and regenerative properties, although their application as adjuncts in melasma remains at the preclinical stage. Limitations: The studies included in this review may demonstrate heterogeneity, as a formal risk-of-bias assessment was not conducted. Further prospective clinical studies may be required to establish the efficacy and safety of nanozyme-based approaches to treatment. Con-clusion: LIOB is a promising approach for addressing melasma and photoaging in terms of uti-lizing pigment fragmentation and triggering regenerative tissue responses in melasma. To moni-tor treatment results non-invasively, CRFF-OCT may provide valuable structural biomarkers as a reference. HPDs are an emerging adjunct to treatment monitoring as well. Protocol registration: The review protocol was not prospectively registered in a publicly accessible systematic review registry. Funding: No specific funding was provided for this systemati review.