title: Collagenase-labile polyurethane urea synthesis and processing into hollow fiber membranes.
abstract: As a means to stimulate wound healing, a hollow fiber membrane system might be placed within a wound bed to provide local and externally regulated controlled delivery of regenerative factors. After sufficient healing, it would be desirable to triggerably degrade these fibers as opposed to pulling them out. Accordingly, a series of enzymatically degradable thermoplastic elastomers was developed as potential hollow fiber base material. Polyurethane ureas (PUUs) were synthesized based on 1, 4-diisocyanatobutane, polycaprolactone (PCL) diol and polyethylene glycol (PEG) at different molar fractions as soft segments, and collagenase-sensitive peptide GGGLGPAGGK-NH2 as a chain extender (defined as PUU-CLxEGy-peptide, where x and y are the respective molar percents). In these polymers, PEG in the polymer backbone decreased tensile strengths and initial moduli of solvent-cast films in the wet state, while increasing water absorption. Collagenase degradation was observed at 75% relative PEG content in the soft segment. Control PUUs with putrescine or nonsense peptide chain extenders did not degrade acutely in collagenase. Conduits electrospun from PUU-CL25EG75-peptide and PUU-CL50EG50-peptide exhibited appropriate mechanical strength and sustained release of a model protein from the tube lumen for 7 days. Collapse of PUU-CL25EG75-peptide tubes occurred after collagenase degradation for 3 days. In conclusion, through molecular design, synthesis and characterization, a collagenase-labile PUU-CL25EG75-peptide polymer was identified that exhibited the desired traits of triggerable lability, processability, and the capacity to act as a membrane to facilitate controlled protein release.
authors.affiliation: McGowan Institute for Regenerative Medicine, ‡Department of Surgery, §Department of Chemical & Petroleum Engineering, and ∥Department of Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania 15219, United States.
authors.forename: Hui-Li
authors.initials: HL
authors.lastname: Fu
authors.forename: Yi
authors.initials: Y
authors.lastname: Hong
authors.forename: Steven R
authors.initials: SR
authors.lastname: Little
authors.forename: William R
authors.initials: WR
authors.lastname: Wagner
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D047009:Hathewaya histolytica / Q000201:enzymology*; D008567:Membranes, Artificial; D003012:Microbial Collagenase / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011140:Polyurethanes / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D008567:Membranes, Artificial; D010455:Peptides; D011140:Polyurethanes; D003012:Microbial Collagenase