Abstract
Introduction: Atrophic acne scarring affects a substantial majority of patients with inflammatory acne and remains one of the most refractory indications in aesthetic and reconstructive dermatology. Mesenchymal stromal cell-derived and plant-derived exosomes are 30–150 nm extracellular vesicles that carry microRNA, growth-factor, and lipid cargo capable of suppressing transforming growth factor-beta 1 (TGF-β1)/SMAD2-3 signalling, reprogramming macrophages towards an M2 phenotype, and restoring organised type I and type III collagen deposition. Their clinical translation, however, is constrained less by intrinsic bioactivity than by the physics of cutaneous delivery: the 15–20 μm stratum corneum is an efficient exclusion filter for nanoscale vesicles. No previous synthesis has interrogated the delivery system itself as the principal determinant of clinical effect, nor mapped the completeness of dose reporting across the human evidence base.
Methods: The study strictly adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines. Eligible designs included randomised controlled trials, cohort studies, case-control studies, cross-sectional studies, and other observational designs reporting exosome or exosome-like extracellular-vesicle therapy delivered to human skin for scar, post-acne, or dermal-remodelling indications. Two reviewers independently screened, extracted, and appraised.
Results: Eighteen primary studies enrolling 472 participants met the eligibility criteria: ten randomised controlled trials (seven split-face, three parallel-group), five prospective observational studies, and three case series. Six randomised comparisons provided extractable data for the primary outcome. The pooled standardised mean difference for global clinical improvement with exosome-augmented delivery versus the identical platform without exosomes was 0.82 (95% CI 0.50–1.13; Z = 5.00; p < 0.000001; I² = 62.1%). The ablative fractional CO₂ laser subgroup yielded a pooled estimate of 0.64 (95% CI 0.40–0.87) with complete homogeneity (I² = 0%). Every comparison in which the delivery platform transiently breached the stratum corneum favoured the exosome arm, whereas the only randomised comparison of topical application to an intact barrier produced a limited and time-decaying effect. Only 16.7% of studies reported any quantitative dose metric, and no study reported dose per unit treated area.
Conclusion: Exosome therapy delivers a clinically meaningful and statistically significant incremental improvement in scar and dermal-remodelling outcomes when—and, on present evidence, only when—it is administered through a delivery platform that transiently breaches the stratum corneum. Device-assisted delivery should therefore be regarded as an obligate component of the intervention. An optimal dose cannot be defined from the existing literature; the field requires a mandatory minimum reporting dataset specifying particle concentration, total particle dose, protein content, treated surface area, characterisation against MISEV criteria, and potency assay results before dose-response modelling becomes possible.