Biocompatibility of injectable resilin-based hydrogels

Vocal folds are connective tissues housed in the larynx, which can be subjected to various injuries and traumatic stimuli that lead to aberrant tissue structural alterations and fibrotic-induced biomechanical stiffening observed in patients with voice disorders. Much effort has been devoted to generate soft biomaterials that are injectable directly to sites of injury. To date, materials applied toward these applications have been largely focused on natural extracellular matrix-derived materials such as collagen, fibrin or hyaluronic acid; these approaches have suffered from the fact that materials are not sufficiently robust mechanically nor offer sufficient flexibility to modulate material properties for targeted injection. We have recently developed multiple resilin-inspired elastomeric hydrogels that possess similar mechanical properties as those reported for vocal fold tissues, and that also show promising in vitro cytocompatibility and in vivo biocompatibility. Here we report studies that test the delivery of resilin-based hydrogels through injection to the subcutaneous tissue in a wild-type mice model; histological and genetic expression outcomes were monitored. The rapid kinetics of crosslinking enabled facile injection and ensured the rapid transition of the viscous resilin precursor solution to a solid-like hydrogel in the subcutaneous space in vivo; the materials exhibited storage shear moduli in the range of 1000-2000 Pa when characterized through oscillatory rheology. Histological staining and gene expression profiles suggested minimal inflammatory profiles three weeks after injection, thereby demonstrating the potential suitability for site-specific in vivo injection of these elastomeric materials. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2229-2242, 2018.