Polysaccharide Derivative for High-Precision Stereolithography 3D Hydrogel Bio-Printing

Light based 3D bioprinting has become a rapidly emerging technology to engineer living cellular constructs towards functional tissues and organs. However, there is still an urgent need to improve the printing resolution, mechanical properties and biocompatibility of current printed cell-laden hydrogels. Here, we developed a novel bioink additive by grafting a light-triggering molecule hydroxyl ortho-nitrobenzyl (NB) to chondroitin sulfate (CS). This new biomacromolecule, called CSNB, can efficiently improve the photo resolution of commonly used bioinks, such as gelatin methacrylate (GelMA) and poly (ethylene glycol) diacrylate (PEGDA), mainly by inhibiting the free radical polymerization at unexposed area during patterned photo-initiation. Fine and clear structure can be manufactured by both digital light processing (DLP) 3D printing or photolithography and the resolution can be increased to 10μm level. Moreover, in contrast to current photoabsorbers used to improve printing resolution, the new biomacromolecule CSNB can increases compressive modulus four-fold compared to pure GelMA hydrogel. In addition, CSNB reduces cytotoxicity due to avoiding burst release of small molecule additives and shows excellent biocompatibility both in vitro and in vivo. Importantly, GelMA/CSNB bioink was successfully used to print multicell-laden hydrogels with complex patterns and supported the proliferation of encapsulated human adipose derived mesenchymal stem cells and HepG2 liver cells in culture for at least one week. CSNB thus represents a biocompatible bioink additive that provides an easy approach to improve printing resolution and increase the mechanical properties of amino containing hydrogels like GelMA. The application of CSNB has important implications for tissue and organ reconstruction as well as for the development of improved in vivo biomimetic research models.