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

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.

A highly adhesive and naturally derived sealant

“…Subcutaneous implantation of GelMA in rats (n=6) was conducted as recently published [36, 41]. After induction of general anesthesia, small separated subcutaneous pockets were bluntly prepared through short dorsal skin incisions (10 mm in length), and 25% (w/v) GelMA samples (n=18) were implanted.…”

Advances in engineering hydrogels

“…For example, elastin is a widely distributed structural protein required to maintain tissue integrity and confer elasticity and is present in tissues such as blood vessels, heart, bladder, and skin. To this end, recombinant tropoelastin, and its enzymatically cross-linked form termed elastin-like polypeptides (ELPs), have been engineered (46, 47). These engineered elastin-based hydrogels typically possess strong elasticity by using a pentapeptide repeat, VPGXG, where X is any amino acid except proline (46).…”

“…To this end, recombinant tropoelastin, and its enzymatically cross-linked form termed elastin-like polypeptides (ELPs), have been engineered (46, 47). These engineered elastin-based hydrogels typically possess strong elasticity by using a pentapeptide repeat, VPGXG, where X is any amino acid except proline (46). They can achieve stretchability of up to ~400% their original lengths (47), which is much higher than most existing naturally derived hydrogels.…”

In vitro and in vivo analysis of visible light crosslinkable gelatin methacryloyl (GelMA) hydrogels

“…Ultraviolet (UV) light is commonly used for photocrosslinking of such materials, as well as commercial products for dental applications. We have recently reported the engineering of highly elastic hydrogels via UV light-mediated crosslinking of chemically modified tropoelastin or elastin-like polypeptides for wound healing and cardiac tissue engineering 9–12 . These UV crosslinked hydrogels exhibited high cytocompatibility for three-dimensional (3D) encapsulated cells in vitro , as well as a negligible immune responses after subcutaneous implantation in rats 13 .…”