Background: Skin scarring can occur after punch biopsies, prohibiting their routine utilization, especially in the central face. Objectives: This paper describes a scarless, 0.33-mm-diameter skin microbiopsy for molecular analysis of skin. Methods: This is was single-center, randomized, prospective study with 15 patients receiving no biopsy or biopsy on the left or right nasolabial fold. Six blinded raters assessed participant photos at baseline, 1 month, and 3 months post biopsy to evaluate for a visualized scar. Patient and Observer Scar Assessment Scale was completed. Additionally, biopsies from various skin regions of body along with arm skin after treatment with a single Erbium-YAG laser were processed for molecular analysis. Results: No patients exhibited scar formation based on evaluation of photographs and patient feedback. There was no mark at the biopsy site 7 days post-procedure. Optical coherence tomography showed a complete closing of the biopsy-punch wound 48 hours post-biopsy. One month post-biopsy, photography reviewers were unable to identify a scar, on average, 90% of the time at 3-month follow-up. Microbiopsies from various anatomical regions were successfully extracted for histology, electron microscopy, and gene expression analysis. Selected skin rejuvenation markers in the biopsies from Erbium-YAG-Treated forearm skin resulted in significant gene upregulation in extracellular matrix molecules at 1 month posttreatment compared with untreated skin. Conclusions: A core microbiopsy of 0.33 mm can be extracted reproducibly for histological, ultrastructural, and gene expression analysis without scarring. This allows repeated sampling for assessment of skin treatments and diseases, including aesthetics and wound-healing progress.
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