This systematic review evaluated the effects of Aloe vera on fibroblast activity and the underlying mechanisms involved in wound healing. The review was conducted in accordance with the PRISMA 2020 guidelines. Literature searches were performed in PubMed, Scopus, and ScienceDirect using the keywords “Aloe vera,” “fibroblast,” and “wound healing.” Original studies published in English or Indonesian were included if they investigated the effects of Aloe vera on fibroblasts or wound-healing processes using in vitro, in vivo, or topical formulation models. Twenty studies met the eligibility criteria. The included studies suggested that Aloe vera supports fibroblast proliferation, migration, viability, and collagen synthesis. In vitro studies further demonstrated increased extracellular matrix production, reduced levels of pro-inflammatory mediators, and enhanced antioxidant defenses. In vivo studies reported accelerated wound closure and enhanced angiogenesis, accompanied by increased expression of VEGF, TGF-β, and PDGF-BB, as well as antimicrobial activity. In addition, Aloe vera-based biomaterials, including hydrogels, scaffolds, bioactive films, and nanomembranes, provided structural support and sustained-release properties that may facilitate tissue regeneration. Overall, the current literature provides promising preclinical evidence that Aloe vera may support multiple mechanisms involved in wound healing. However, high-quality clinical studies are still required to establish its efficacy, safety, optimal formulation, and translational applicability in humans.
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