Three-Dimensional-Printable Thermo/Photo-Cross-Linked Methacrylated Chitosan–Gelatin Hydrogel Composites for Tissue Engineering

Biomimetic constructs imitating the functions, structures, and compositions of normal tissues are of great importance for tissue repair and regeneration. Three-dimensional (3D) printing is an innovative method to construct intricate biomimetic 3D tissue engineering scaffolds with spatiotemporal deposition of materials to control the intrinsic architectural organization and functional performance of the scaffold. However, due to the lack of bioinks with suitable printability, high structural integrity, and biological compatibility, producing constructs that mimic the anisotropic 3D extracellular environments remains a challenge. Here, we present a printable hydrogel ink based on methylacrylate-modified chitosan (ChMA) and gelatin (GelMA) embedding nanohydroxyapatite (nano-Hap). This polymer composite is first physically cross-linked by thermal gelation for postprinting structural stability, followed by covalent photo-cross-linking of ChMA and GelMA to form a long-term stable structure. The rheological behavior of the hydrogels and the mechanical strengths of the printed constructs are tuned by adjusting the content of GelMA, which in turn enhances the shape retention after printing and enables the precise deposition of multilayered 3D scaffolds. Moreover, the formulated biomaterial inks exhibit biological characteristics that effectively support the spreading and proliferation of stem cells seeded on the scaffolds after 7 days of in vitro culture. Adding Hap has minor influences on the mechanical rigidity and cytocompatibility of the hydrogels compared with the group free of Hap. Together, the printable biomaterial inks with shear thinning and good structural integrity, along with biological cues, are promising for tissue engineering application.