Three-dimensional (3D) bioprinting has attracted considerable attention for producing 3D engineered cellular microenvironments that replicate complex and sophisticated native extracellular matrices (ECM) as well as the spatiotemporal gradients of numerous physicochemical and biological cues. Although various hydrogel-based bioinks have been reported, the development of advanced bioink materials that can reproduce the complexity of ECM accurately and mimic the intrinsic property of laden cells is still a challenge. This paper reports 3D printable bioinks composed of phenol-rich gelatin (GHPA) and graphene oxide (GO) as a component for a myogenesis-inducing material, which can form a hydrogel network in situ by a dual enzyme-mediated cross-linking reaction. The in situ curable GO/GHPA hydrogel can be utilized successfully as 3D-printable bioinks to provide suitable cellular microenvironments with facilitated myogenic differentiation of C2C12 skeletal myoblasts. Overall, we suggest that functional bioinks may be useful in muscle tissue engineering and regenerative medicine.
Reactive oxygen species (ROS) have been implicated as a critical modulator for various therapeutic applications such as treatment of vascular disorders, wound healing, and cancer treatment. Specifically, growing evidence has recently demonstrated that transient or low levels of hydrogen peroxide (HO) facilitates tissue regeneration and wound repair through acute oxidative stress that can evaluate intracellular ROS levels in cells or tissues. Herein, we report a gelatin-based HO-releasing hydrogel formed by dual enzyme-mediated reaction using horseradish peroxidase and glucose oxidase (GO ). The release behavior of HO from the hydrogel matrices can be precisely controlled by varying the GO concentrations. We demonstrate that HO-releasing hydrogels with the optimal condition increase transient upregulation of intracellular ROS levels in the endothelial cells (ECs), enhance proliferative activities of ECs in vitro, and facilitate neovascularization in ovo. We suggest that our HO-releasing hydrogels hold great potential as an injectable and dynamic matrix for the treatment of vascular disorders as well as in tissue regenerative medicine.
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