Introduction
Oral and ocular dryness are frequent consequences of autoimmune diseases such as Sjögren’s syndrome, endocrinological pathologies, head and neck radiotherapy and age related atrophy.
Conventional therapies are mainly symptomatic. In recent years, however, regenerative approaches based on PRP, stem cells, exosomes, tissue engineering and mechanobiology have emerged as promising alternatives.
Platelet-Rich Plasma (PRP)
PRP, through the release of growth factors such as PDGF, TGF-β, VEGF, IGF-1 and EGF, showed positive effects in the regeneration of irradiated or autoimmune-damaged tissues. Intraductal PRP injections improved salivary flow in irradiated patients (Alves, 2020), while PRP eye drops reduced dry eye symptoms (Rao, 2021; Lopez-Plandolit, 2021).
Pietro Gentile contributed with key studies on optimizing platelet concentration to maximize regenerative potential (Gentile, 2020).
Mesenchymal Stem Cell (MSC) Therapies
MSCs have demonstrated a key role in glandular regeneration, both in animal models and in clinical studies in patients with Sjögren’s syndrome or radiation-induced xerostomia. They act through differentiation into acinar-like cells and mainly via paracrine effects, releasing immunomodulatory and trophic factors (Li, 2023; Zhang, 2025; Marinković, 2023).
Exosome-Based Therapies
Exosomes derived from MSCs and other stem cells carry miRNAs, proteins and growth factors that reduce inflammation and stimulate gland regeneration. Studies in animal models (Hu, 2023; Du, 2025) and clinical trials (Habibi, 2025) reported improved salivary and lacrimal secretion and reduction of inflammatory markers.Tissue Engineering ApproachesSalivary and lacrimal organoids represent an innovative approach for gland replacement. Organoids derived from progenitor cells or from iPSCs have shown the ability to reproduce gland structure and function and, once transplanted, partially restored secretion in animal models (Yoon, 2022; Asal, 2022; Jeon, 2024).
Mechanobiology
Mechanobiology plays a fundamental role:composizione e consistenza della matrice, stimoli meccanici di tensione, pressione idrostatica, trazione, come anche stimoli ultrasonici e segnali elettrici modulano la differenziazione cellulare e la secrezione (Rizzo, 2025): soft massage, matrix stiffness, ultrasonic stimuli, and electrical signals modulate cell differentiation and secretion. Recent studies highlighted the role of Piezo1 channels in gland morphogenesis (Pokharel, 2023), the importance of controlled hydrogel stiffness (Pillai, 2022), and the efficacy of pulsed ultrasound in restoring secretion (Xu, 2015).
Conclusions
Current regenerative strategies pave the way for a future in which xerostomia and dry eye can be treated with integrated biological, bioengineering, and mechanobiological approaches.
The combination of PRp, MSCs, exosomes, organoids and physical stimuli, represents the new paradigm of glandular regeneration.
References
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