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.

Rational design of biodegradable thermoplastic polyurethanes for tissue repair

“…4 D) [ 67 ]. Furthermore, a collagenase-sensitive peptide, GGGLGPAGGK-NH 2 , was introduced into the PU backbone as a chain extender to obtain a collagenase labile biodegradable polymer for wound healing [ 145 ]. A dipeptide of Gly–Leu linkage is the cleavage site of various matrix metalloproteinases (MMPs), and a Gly–Leu-based chain extender was introduced into a PU to support mouse embryonic fibroblasts growth [ 146 ].…”

Engineering Biomaterials for Enhanced Tissue Regeneration

“…In this approach, labile chemical groups are conjugated into the backbone of polymers that can be degraded by physical or chemical signals, such as nearinfrared light [35], ultraviolet light [36•], ultrasound [37,38], redox [4], various enzymes [39,40], and pH changes [41]. As an example, a peptide-conjugated polymer was generated, which underwent degradation when it was exposed to collagenase [39]. When designing these systems, the physical or chemical cue must be carefully designed to avoid off target effects.…”

Rapidly Biodegrading PLGA-Polyurethane Fibers for Sustained Release of Physicochemically Diverse Drugs

“…10 A subclass of segmented, linear, biodegradable PU elastomers incorporate hard and soft segments in which backbone chain bonds can be hydrolyzed to biocompatible degradation products. 11 Various strategies have been employed to alter the degradation profiles and mechanical properties of biodegradable polyurethanes, including varying the soft 12–15 or hard 16 segment composition, incorporation of acid-cleavable hydrazone 17,18 or collagenase-labile 19 linkers, and varying the hard to soft segment ratio. 20–23 Synthesis of segmented biodegradable PUs allows for engineering the polymer structure, such as the hard to soft segment ratio, or incorporation of pendant groups in order to exert control of the release mechanisms of physicochemically diverse drugs.…”