Synergistic effects of laminin-1 peptides, VEGF and FGF9 on salivary gland regeneration

• Published in: Acta biomaterialia 2019-06, Vol.91, p.186-194
• Main Authors: Nam, Kihoon, Dean, Spencer M., Brown, Callie T., Smith, Randall J., Lei, Pedro, Andreadis, Stelios T., Baker, Olga J.
• Format: Article
• Language: English
• Subjects: Aging; Angiogenesis; Animals; Biomaterial; Extracellular matrix; Female; Fibrin; Fibroblast growth factor 9; Fibroblast Growth Factor 9 - chemistry; Fibroblast Growth Factor 9 - pharmacology; Fibroblast growth factor receptor 9; Growth factors; Humans; Hydrogel; Hydrogels; Hydrogels - chemistry; Hydrogels - pharmacology; Laminin; Laminin - chemistry; Laminin - pharmacology; Mice; Neovascularization, Physiologic - drug effects; Neurogenesis; Neurogenesis - drug effects; Peptides; Peptides - chemistry; Peptides - pharmacology; Radiation; Radiation therapy; Recovery of function; Regeneration; Regeneration - drug effects; Saliva; Salivary gland; Salivary glands; Salivary Glands - injuries; Salivary Glands - physiology; Scaffold; Secretion; Sjogren's syndrome; Synergistic effect; Tissue engineering; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - chemistry; Vascular Endothelial Growth Factor A - pharmacology
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2019.04.049

[Display omitted] Hyposalivation is associated with radiation therapy, Sjögren’s syndrome and/or aging, and is a significant clinical problem that decreases oral health and overall health in many patients and currently lacks effective treatment. Hence, methods to regenerate salivary glands and restore saliva secretion are urgently needed. To this end, this study describes the modification of fibrin hydrogels with a combination of laminin-1 peptides (YIGSR and A99) and human growth factors (vascular endothelial growth factor and fibroblast growth factor 9) to enhance regeneration in a salivary gland injury mouse model. Our results indicate that these fortified hydrogels enhanced angiogenesis and neurogenesis while promoting formation of acinar structures, thereby leading to enhanced saliva secretion. Such functional recovery indicates salivary gland regeneration and suggests that our technology may be useful in promoting gland regeneration and reversing hyposalivation in a clinical setting. We engineered Fibrin Hydrogels (FH) to contain multiple regenerative cues including laminin-1 peptides (L1p) and growth factors (GFs). L1p and GF modified FH were used to induce salivary gland regeneration in a wounded mouse model. Treatment with L1p and GF modified FH promoted salivary epithelial tissue regeneration, vascularization, neurogenesis and healing as compared to L1p-FH or FH alone. Results indicate that L1p and GF modified FH can be used for future therapeutic applications.