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      A Highly Elastic and Rapidly Crosslinkable Elastin-Like Polypeptide-Based Hydrogel for Biomedical Applications

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          Abstract

          Elastin-like polypeptides (ELPs) are promising for biomedical applications due to their unique thermoresponsive and elastic properties. ELP-based hydrogels have been produced through chemical and enzymatic crosslinking or photocrosslinking of modified ELPs. Herein, a photocrosslinked ELP gel using only canonical amino acids is presented. The inclusion of thiols from a pair of cysteine residues in the ELP sequence allows disulfide bond formation upon exposure to UV light, leading to the formation of a highly elastic hydrogel. The physical properties of the resulting hydrogel such as mechanical properties and swelling behavior can be easily tuned by controlling ELP concentrations. The biocompatibility of the engineered ELP hydrogels is shown in vitro as well as corroborated in vivo with subcutaneous implantation of hydrogels in rats. ELP constructs demonstrate long-term structural stability in vivo, and early and progressive host integration with no immune response, suggesting their potential for supporting wound repair. Ultimately, functionalized ELPs demonstrate the ability to function as an in vivo hemostatic material over bleeding wounds.

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          Most cited references67

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          Hydrogels for tissue engineering.

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            Highly stretchable and tough hydrogels.

            Hydrogels are used as scaffolds for tissue engineering, vehicles for drug delivery, actuators for optics and fluidics, and model extracellular matrices for biological studies. The scope of hydrogel applications, however, is often severely limited by their mechanical behaviour. Most hydrogels do not exhibit high stretchability; for example, an alginate hydrogel ruptures when stretched to about 1.2 times its original length. Some synthetic elastic hydrogels have achieved stretches in the range 10-20, but these values are markedly reduced in samples containing notches. Most hydrogels are brittle, with fracture energies of about 10 J m(-2) (ref. 8), as compared with ∼1,000 J m(-2) for cartilage and ∼10,000 J m(-2) for natural rubbers. Intense efforts are devoted to synthesizing hydrogels with improved mechanical properties; certain synthetic gels have reached fracture energies of 100-1,000 J m(-2) (refs 11, 14, 17). Here we report the synthesis of hydrogels from polymers forming ionically and covalently crosslinked networks. Although such gels contain ∼90% water, they can be stretched beyond 20 times their initial length, and have fracture energies of ∼9,000 J m(-2). Even for samples containing notches, a stretch of 17 is demonstrated. We attribute the gels' toughness to the synergy of two mechanisms: crack bridging by the network of covalent crosslinks, and hysteresis by unzipping the network of ionic crosslinks. Furthermore, the network of covalent crosslinks preserves the memory of the initial state, so that much of the large deformation is removed on unloading. The unzipped ionic crosslinks cause internal damage, which heals by re-zipping. These gels may serve as model systems to explore mechanisms of deformation and energy dissipation, and expand the scope of hydrogel applications.
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              Principles of Polymerization

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                Author and article information

                Journal
                Advanced Functional Materials
                Adv. Funct. Mater.
                Wiley
                1616301X
                August 2015
                August 2015
                July 01 2015
                : 25
                : 30
                : 4814-4826
                Affiliations
                [1 ]Biomaterials Innovation Research Center; Department of Medicine; Brigham and Women's Hospital; Harvard Medical School; Boston MA 02139 USA
                [2 ]Harvard-MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology; Cambridge MA 02139 USA
                [3 ]Department of Biological Engineering; Massachusetts Institute of Technology; Cambridge MA 02139 USA
                [4 ]Laboratory for Cell and Tissue Engineering; Department of Obstetrics; University Hospital Zurich; Zürich CH-8091 Switzerland
                [5 ]Wyss Institute for Biologically Inspired Engineering; Harvard University; Boston MA 02115 USA
                [6 ]Department of Cardiovascular Surgery; Heinrich Heine University; 40225 Duesseldorf Germany
                [7 ]Department of Materials Science and Engineering; University of Toronto; Toronto Ontario M5S1A4 Canada
                [8 ]Center of Nanotechnology; King Abdulaziz University; Jeddah 21589 Saudi Arabia
                [9 ]Department of Chemical Engineering; Massachusetts Institute of Technology; Cambridge MA 02139 USA
                [10 ]Department of Chemical Engineering; Northeastern University; Boston MA 02115-5000 USA
                [11 ]Department of Physics; King Abdulaziz University; Jeddah 21569 Saudi Arabia
                Article
                10.1002/adfm.201501489
                4623594
                26523134
                20b28303-9255-4e87-9ddd-52e41fdf4f40
                © 2015

                http://doi.wiley.com/10.1002/tdm_license_1.1

                http://onlinelibrary.wiley.com/termsAndConditions#vor

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