title: Surgical sealants with tunable swelling, burst pressures, and biodegradation rates.
abstract: We developed two types of polyethylene glycol (PEG)-based surgical sealants, which we have termed the PER and PRO series. In one, the PRO series, an 8-arm PEG containing activated carbonyl end-groups was reacted with a 4-armed amino-PEG. In the second, the PER series, a 4-arm PEG containing bi-functional end groups with four azides and four activated esters was reacted by strain-promoted alkyne-azide cycloaddition with a 4-arm cyclooctyne-PEG to give a near-ideal Tetra-PEG hydrogel. The sealants showed predictably tunable strength, swelling, adhesion, and gelation properties. The gels were compared to commercially available PEG-based sealants and exhibit physical properties equivalent to or better than the standards. Variants of each gel-format were prepared that contained a β-eliminative cleavable linker in the crosslinks to control degradation rate. Linkers of this type self-cleave with half-lives spanning from hours to years, and offer the unique ability to precisely tune the degradation to match the healing process. In addition, these linkers could serve as cleavable tethers for controlled drug release. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1602-1611, 2017.
authors.affiliation: ProLynx, 455 Mission Bay Blvd. South, Suite 145, San Francisco, California, 94158.
authors.forename: Jeff
authors.initials: J
authors.lastname: Henise
authors.affiliation: ProLynx, 455 Mission Bay Blvd. South, Suite 145, San Francisco, California, 94158.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Hearn
authors.affiliation: ProLynx, 455 Mission Bay Blvd. South, Suite 145, San Francisco, California, 94158.
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Santi
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kamata
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Sakai
authors.affiliation: ProLynx, 455 Mission Bay Blvd. South, Suite 145, San Francisco, California, 94158.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Ashley
mesh_terms: D063566:Biodegradable Plastics / Q000737:chemistry*; D006801:Humans; D008422:Materials Testing; D011092:Polyethylene Glycols / Q000737:chemistry*; D011312:Pressure; D014014:Tissue Adhesives / Q000737:chemistry*
chemical_list: D063566:Biodegradable Plastics; D014014:Tissue Adhesives; D011092:Polyethylene Glycols
keywords: cleavable linkers; controlled degradation; hydrogel; surgical sealants; tetra-PEG hydrogels