SUMMARY Flap necrosis and graft failure remain significant sources of morbidity in reconstructive and aesthetic surgery, yet no cell-free biological adjunct has been established to improve tissue survival after transfer. Exosomes are nano-sized extracellular vesicles capable of simultaneously modulating angiogenesis, inflammation, apoptosis, and oxidative stress, and have been investigated as candidate regenerative adjuncts in plastic surgery. This PROSPERO-registered systematic review and meta-analysis (CRD420251146650), conducted per PRISMA 2020, searched PubMed, OVID, Scopus, Web of Science, and Google Scholar through September 2025 and included 24 animal studies (19 flap; 5 skin graft). Flap and graft studies were analysed as separate populations. Random-effects meta-analysis suggested increased flap survival (k=19; MD 35.54%; 95% CI 25.11–45.97; p<0.0001) and angiogenesis (k=19; SMD 3.60; 95% CI 2.66–4.54; p<0.00001). However, heterogeneity was extreme (I² 76–97%), and funnel plot asymmetry with significant Egger's tests (both p<0.001) indicated substantial small-study effects; the true effect is likely considerably smaller than these pooled estimates suggest, which should therefore be interpreted with caution. Perfusion, VEGF expression, and apoptosis generally favoured exosomes in narrative synthesis. In skin graft models, 4 of 5 studies reported improved graft take by days 10–14, but certainty was low. Allocation concealment was unreported in all studies and blinding unclear in most, representing a major methodological limitation that may further inflate observed effects. Preclinical evidence provides a biological rationale, but findings remain exploratory and hypothesis-generating. Standardised preclinical replication is required before clinical translation can be considered.
Perkasa-Hendropriyono et al. (Mon,) studied this question.