Laminin-1 Peptides Conjugated to Fibrin Hydrogels Promote Salivary Gland Regeneration in Irradiated Mouse Submandibular Glands

Abstract

Previous studies demonstrated that salivary gland morphogenesis and differentiation are enhanced by modification of fibrin hydrogels chemically conjugated to Laminin-1 peptides. Specifically, Laminin-1 peptides (A99: CGGALRGDN-amide and YIGSR: CGGADPGYIGSRGAA-amide) chemically conjugated to fibrin promoted formation of newly organized salivary epithelium both in vitro (e.g., using organoids) and in vivo (e.g., in a wounded mouse model). While these studies were successful, the model’s usefulness for inducing regenerative patterns after radiation therapy remains unknown. Therefore, the goal of the current study was to determine whether transdermal injection with the Laminin-1 peptides A99 and YIGSR chemically conjugated to fibrin hydrogels promotes tissue regeneration in irradiated salivary glands. Results indicate that A99 and YIGSR chemically conjugated to fibrin hydrogels promote formation of functional salivary tissue when transdermally injected to irradiated salivary glands. In contrast, when left untreated, irradiated salivary glands display a loss in structure and functionality. Together, these studies indicate that fibrin hydrogel-based implantable scaffolds containing Laminin-1 peptides promote secretory function of irradiated salivary glands.

Hydrogels for the treatment of oral and maxillofacial diseases: current research, challenges, and future directions

“…Moreover, MG originated from rat sarcoma which is rich in extracellular matrix protein, thus performs significant variability between different batches and tumorigenicity, limiting its application for salivary gland reconstruction 206,215 . Aiming at developing safer hydrogel scaffolds, researchers fabricated hydrogels composed of different polymer molecules, including natural hydrogels (e.g., Matrigel ® , decellularized ECM, laminin I/IV) and synthetic hydrogels (e.g., PEG, PLGA) 206,217,221,222 .…”

“…Hydrogel scaffolds can also promote secretory function of irradiated salivary glands in vivo. A laminin-1 peptides (A99, YIGSR) modified fibrin hydrogel was injected into irradiated salivary glands, exhibiting promotion to formation of functional salivary tissue 221 . Therefore, the in vitro culture and drug testing of hydrogel in salivary gland tissue, and transplantation in vivo to promote the regeneration of salivary gland tissue may provide a novel and prospective approach for the treatment of irradiation salivary gland damage.…”

“…206,215 Aiming at developing safer hydrogel scaffolds, researchers fabricated hydrogels composed of different polymer molecules, including natural hydrogels (e.g., Matrigel®, decellularized ECM, laminin I/IV) and synthetic hydrogels (e.g., PEG, PLGA). 206,217,221,222 Moreover, the addition of regulators in hydrogels such as laminin-1 peptides (e.g., YIGSR, A99), human growth factors (e.g., VEGF, FGF9), matrix metalloproteinase (MMP) and integrin resulted in synergistic effects on salivary gland proliferation and differentiation. 223,224 Recent evidence suggests that the growth of salivary gland tissue can be regulated in vitro through modifying hydrogel with peptide.…”

“…, PEG, PLGA). 206,217,221,222 Moreover, the addition of regulators in hydrogels such as laminin-1 peptides ( e.g. , YIGSR, A99), human growth factors ( e.g.…”

Radioprotective drug screening in a salivary gland tissue chip

“…Current treatment options, including sialogogues, mouthwashes, and chewing gum, only provide temporary relief and there is no cure [2]. Several strategies have been proposed to alleviate this damage, including cell/hydrogel transplantation [4][5][6][7] and gene therapy [8][9][10][11]. Despite promising results, these methods have remained experimental and are targeted toward patients already experiencing xerostomia.…”