title: L1 Peptide-Conjugated Fibrin Hydrogels Promote Salivary Gland Regeneration.
abstract: Hyposalivation contributes to dental caries, periodontitis, and microbial infections. Additionally, it impairs activities of daily living (e.g., speaking, chewing, and swallowing). Treatments for hyposalivation are currently limited to medications (e.g., the muscarinic receptor agonists pilocarpine and cevimeline) that induce saliva secretion from residual acinar cells and the use of saliva substitutes. However, given that these therapies provide only temporary relief, the development of alternative treatments to restore gland function is essential. Previous studies demonstrated that laminin 1 (L1) is critical for intact salivary cell cluster formation and organization. However, the full L1 sequence is not suitable for clinical applications, as each protein domain may contribute to unwanted effects, such as degradation, tumorigenesis, and immune responses that, when compounded, outweigh the potential benefits provided by their sum. Although the L1 peptides YIGSR and A99 linked to fibrin hydrogels (FHs) promote intact salivary epithelial formation in vitro, little is known about their role during salivary gland regeneration in vivo. Therefore, the goal of this study was to demonstrate whether L1 peptides conjugated to FHs promote tissue regeneration in a wound-healing model of mouse submandibular glands (mSMGs). Our results suggest that YIGSR-A99 peptides, chemically conjugated to FHs and applied to wounded mSMGs in vivo, formed new organized salivary tissue. In contrast, wounded mSMGs treated with FHs alone or in the absence of a scaffold showed disorganized collagen formation and poor tissue healing. Together these studies indicate that damaged salivary gland tissue can grow and differentiate when treated with FHs containing L1 peptides.
authors.affiliation: 1 School of Dentistry, The University of Utah, Salt Lake City, UT, USA.
authors.forename: K
authors.initials: K
authors.lastname: Nam
authors.affiliation: 1 School of Dentistry, The University of Utah, Salt Lake City, UT, USA.
authors.forename: C-S
authors.initials: CS
authors.lastname: Wang
authors.affiliation: 1 School of Dentistry, The University of Utah, Salt Lake City, UT, USA.
authors.forename: C L M
authors.initials: CLM
authors.lastname: Maruyama
authors.affiliation: 2 Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY, USA.
authors.forename: P
authors.initials: P
authors.lastname: Lei
authors.affiliation: 2 Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY, USA.|3 Department of Biomedical Engineering, School of Engineering and Applied Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA.|4 Center of Bioinformatics and Life Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA.
authors.forename: S T
authors.initials: ST
authors.lastname: Andreadis
authors.affiliation: 1 School of Dentistry, The University of Utah, Salt Lake City, UT, USA.
authors.forename: O J
authors.initials: OJ
authors.lastname: Baker
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000494:pharmacology; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000502:physiology; D005337:Fibrin / Q000494:pharmacology*; D020100:Hydrogels / Q000138:chemical synthesis / Q000494:pharmacology*; D007797:Laminin / Q000494:pharmacology*; D051379:Mice; D018613:Microscopy, Confocal; D012038:Regeneration; D013194:Staining and Labeling; D013363:Submandibular Gland / Q000187:drug effects* / Q000502:physiology*; D054457:Tissue Scaffolds; D014945:Wound Healing / Q000187:drug effects
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D007797:Laminin; C121346:laminin 1; D005337:Fibrin
keywords: biocompatible materials; bioengineering; extracellular matrix; laminin; saliva; wound healing