title: Enzymatically degradable mussel-inspired adhesive hydrogel.
abstract: Mussel-inspired adhesive hydrogels represent innovative candidate medical sealants or glues. In the present work, we describe an enzyme-degradable mussel-inspired adhesive hydrogel formulation, achieved by incorporating minimal elastase substrate peptide Ala-Ala into the branched poly(ethylene glycol) (PEG) macromonomer structure. The system takes advantage of neutrophil elastase expression upregulation and secretion from neutrophils upon recruitment to wounded or inflamed tissue. By integrating adhesive degradation behaviors that respond to cellular cues, we expand the functional range of our mussel-inspired adhesive hydrogel platforms. Rapid (<1 min) and simultaneous gelation and adhesion of the proteolytically active, catechol-terminated precursor macromonomer was achieved by addition of sodium periodate oxidant. Rheological analysis and equilibrium swelling studies demonstrated that the hydrogel is appropriate for soft tissue-contacting applications. Notably, hydrogel storage modulus (G') achieved values on the order of 10 kPa, and strain at failure exceeded 200% strain. Lap shear testing confirmed the material's adhesive behavior (shear strength: 30.4 ± 3.39 kPa). Although adhesive hydrogel degradation was not observed during short-term (27 h) in vitro treatment with neutrophil elastase, in vivo degradation proceeded over several months following dorsal subcutaneous implantation in mice. This work represents the first example of an enzymatically degradable mussel-inspired adhesive and expands the potential biomedical applications of this family of materials.
authors: Biomedical Engineering Department, Northwestern University, Evanston, Illinois 60208, United States.
authors: Carrie E
authors: CE
authors: Brubaker
authors: Phillip B
authors: PB
authors: Messersmith
mesh_terms: D000409:Alanine / Q000737:chemistry; D000818:Animals; D049872:Bivalvia / Q000378:metabolism; D002448:Cell Adhesion; D020100:Hydrogels / Q000138:chemical synthesis* / Q000737:chemistry; D019272:Leukocyte Elastase / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D011092:Polyethylene Glycols / Q000737:chemistry; D012212:Rheology; D014014:Tissue Adhesives / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D020100:Hydrogels; D014014:Tissue Adhesives; D011092:Polyethylene Glycols; D019272:Leukocyte Elastase; D000409:Alanine