title: Effects of crosslinking on the mechanical properties, drug release and cytocompatibility of protein polymers.
abstract: Recombinant elastin-like protein polymers are increasingly being investigated as component materials of a variety of implantable medical devices. This is chiefly a result of their favorable biological properties and the ability to tailor their physical and mechanical properties. In this report, we explore the potential of modulating the water content, mechanical properties, and drug release profiles of protein films through the selection of different crosslinking schemes and processing strategies. We find that the selection of crosslinking scheme and processing strategy has a significant influence on all aspects of protein polymer films. Significantly, utilization of a confined, fixed volume, as well as vapor-phase crosslinking strategies, decreased protein polymer equilibrium water content. Specifically, as compared to uncrosslinked protein gels, water content was reduced for genipin (15.5%), glutaraldehyde (GTA, 24.5%), GTA vapor crosslinking (31.6%), disulfide (SS, 18.2%) and SS vapor crosslinking (25.5%) (P<0.05). Distinct crosslinking strategies modulated protein polymer stiffness, strain at failure and ultimate tensile strength (UTS). In all cases, vapor-phase crosslinking produced the stiffest films with the highest UTS. Moreover, both confined, fixed volume and vapor-phase approaches influenced drug delivery rates, resulting in decreased initial drug burst and release rates as compared to solution phase crosslinking. Tailored crosslinking strategies provide an important option for modulating the physical, mechanical and drug delivery properties of protein polymers.
authors.affiliation: Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, GA 30332, USA.
authors.forename: Adam W
authors.initials: AW
authors.lastname: Martinez
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Caves
authors.forename: Swathi
authors.initials: S
authors.lastname: Ravi
authors.forename: Wehnsheng
authors.initials: W
authors.lastname: Li
authors.forename: Elliot L
authors.initials: EL
authors.lastname: Chaikof
mesh_terms: D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004220:Disulfides / Q000494:pharmacology; D016503:Drug Delivery Systems; D004549:Elastin / Q000494:pharmacology*; D005353:Fibronectins / Q000494:pharmacology; D005976:Glutaral / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D039823:Iridoids / Q000494:pharmacology; D055595:Mechanical Phenomena / Q000187:drug effects*; D020123:Sirolimus / Q000494:pharmacology*; D014867:Water / Q000737:chemistry
chemical_list: D003432:Cross-Linking Reagents; D004220:Disulfides; D005353:Fibronectins; D039823:Iridoids; D014867:Water; D004549:Elastin; C007834:genipin; D005976:Glutaral; D020123:Sirolimus
keywords: Crosslinking; Drug release; Mechanical properties; Protein polymer