title: Development of poly(ethylene glycol) hydrogels for salivary gland tissue engineering applications.
abstract: More than 40,000 patients are diagnosed with head and neck cancers annually in the United States with the vast majority receiving radiation therapy. Salivary glands are irreparably damaged by radiation therapy resulting in xerostomia, which severely affects patient quality of life. Cell-based therapies have shown some promise in mouse models of radiation-induced xerostomia, but they suffer from insufficient and inconsistent gland regeneration and accompanying secretory function. To aid in the development of regenerative therapies, poly(ethylene glycol) hydrogels were investigated for the encapsulation of primary submandibular gland (SMG) cells for tissue engineering applications. Different methods of hydrogel formation and cell preparation were examined to identify cytocompatible encapsulation conditions for SMG cells. Cell viability was much higher after thiol-ene polymerizations compared with conventional methacrylate polymerizations due to reduced membrane peroxidation and intracellular reactive oxygen species formation. In addition, the formation of multicellular microspheres before encapsulation maximized cell-cell contacts and increased viability of SMG cells over 14-day culture periods. Thiol-ene hydrogel-encapsulated microspheres also promoted SMG proliferation. Lineage tracing was employed to determine the cellular composition of hydrogel-encapsulated microspheres using markers for acinar (Mist1) and duct (Keratin5) cells. Our findings indicate that both acinar and duct cell phenotypes are present throughout the 14 day culture period. However, the acinar:duct cell ratios are reduced over time, likely due to duct cell proliferation. Altogether, permissive encapsulation methods for primary SMG cells have been identified that promote cell viability, proliferation, and maintenance of differentiated salivary gland cell phenotypes, which allows for translation of this approach for salivary gland tissue engineering applications.
authors.affiliation: 1Department of Biomedical Engineering, University of Rochester, Rochester, New York.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Shubin
authors.affiliation: 1Department of Biomedical Engineering, University of Rochester, Rochester, New York.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Felong
authors.affiliation: 1Department of Biomedical Engineering, University of Rochester, Rochester, New York.
authors.forename: Dean
authors.initials: D
authors.lastname: Graunke
authors.affiliation: 2Center for Oral Biology, University of Rochester, Rochester, New York.|3Department of Biomedical Genetics, University of Rochester, Rochester, New York.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Ovitt
authors.affiliation: 1Department of Biomedical Engineering, University of Rochester, Rochester, New York.|2Center for Oral Biology, University of Rochester, Rochester, New York.|4Department of Chemical Engineering, University of Rochester, Rochester, New York.|5Center for Musculoskeletal Research, Rochester, New York.
authors.forename: Danielle S W
authors.initials: DS
authors.lastname: Benoit
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods; D003094:Collagen / Q000737:chemistry; D005260:Female; D020100:Hydrogels / Q000138:chemical synthesis* / Q000627:therapeutic use; D015227:Lipid Peroxidation; D008689:Methacrylates / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D015394:Molecular Structure; D018384:Oxidative Stress; D010455:Peptides / Q000138:chemical synthesis; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D058105:Polymerization; D017382:Reactive Oxygen Species / Q000378:metabolism; D013363:Submandibular Gland / Q000166:cytology*; D013438:Sulfhydryl Compounds / Q000737:chemistry; D023822:Tissue Engineering / Q000379:methods*; D014987:Xerostomia / Q000628:therapy
chemical_list: D020100:Hydrogels; D008689:Methacrylates; D010455:Peptides; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; C524499:polyethylene glycol methacrylate; D011092:Polyethylene Glycols; D003094:Collagen