Anna Calabrò, Giulia Accardi, Alexander Batista-Duharte, Mattia Emanuela Ligotti, Alejandra Pera, Chiara Puleo, M. Soresi, G Candore, Anna Aiello
Tissue repair is a finely organized process that progresses via a series of phases, including hemostasis, inflammation, proliferation, and remodeling, which are coordinated by immune-stromal interactions. Aging profoundly dysregulates these processes through mechanisms such as immunosenescence and inflammaging, cellular senescence, chronic inflammation, and extracellular matrix alterations, ultimately contributing to typical age-related progression. This review discusses the immune mechanisms that govern physiological tissue healing, as well as the age-related perturbations that lead to ulcerative and fibrotic diseases. It also highlights the potential application of extracellular vesicles (EVs), both mammalian and plant-derived, as a stable and low-immunogenicity mediator to modulate and re-establish repair homeostasis. Translational hurdles such as EV standardization, dosing, safety assessment, and manufacturing are critically discussed to promote their use in geroscience, regenerative medicine, and dermatology.