Advantages of photo-curable collagen-based cell-laden bioinks compared to methacrylated gelatin (GelMA) in digital light processing (DLP) and extrusion bioprinting

The development of cell-laden bioinks that possess high biocompatibility and printability is crucial in the field of bioprinting for the creation of cell embedded tissue engineering scaffolds. As widely known, methacrylated gelatin (GelMA) is one of the most commonly used photo-crosslinkable bioink for cell-laden bioprinting with different printing methods, but GelMA is the derivative of gelatin, so it loses the unique triple-helix molecular structure of collagen and may not be able to successfully activate the cellular pathways or facilitate cell-matrix interaction as effectively as collagen. Recently, methacrylated collagen (CMA) was developed to be an alternative photocrosslinkable bioink with a good bioactivity, but its low printability and biocompatibility limited that application in tissue engineering. In this study, the synthetic process for CMA was improved by synthesizing under 4 °C and using acidic aqueous solution as solvent. Our CMA bioinks were demonstrated a similar printability as GelMA in extrusion bioprinting, while a better formability in digital light processing (DLP). To further analyze the bioactive properties, CMA bioinks were encapsulated with Schwann cells (SCs) and bone mesenchymal stem cells (BMSCs) for printing. SCs-laden CMA bioinks had a significantly higher proliferation rate and expression of neural stem cell-associated genes than GelMA in DLP bioprinting. While, BMSCs-laden CMA bioinks demonstrated >95% cellular viability, better cell spreading and higher expression of osteogenesis-related genes than that of GelMA. Overall, we speculate that the CMA-based bioink developed in this study could be potential bioinks for 3D cell-laden bioprinting in the future.