Novel bioinks from UV-responsive norbornene-functionalized carboxymethyl cellulose macromers

Abstract

3D printing has significantly progressed in the past decade and become a potentially powerful biomanufacturing approach for tissue and organ printing. Availability of diverse hydrogel-based bioink formulations, particularly bioinks allowing biochemical functionalization, stimuli responsiveness, and control over mechanical and degradation properties are crucial for bioprinting to reach its full potential. In this study, we report two novel bioink platforms from norbornene modified cellulose-based macromers, either with an amide, norbornene CMC (NorCMC), or an ester linker, carbic (norbornene) functionalized CMC (cCMC). Both of the bioink formulations show autogelation in the absence of UV light, which allow us to adjust the viscosity of the ink formulation. Bioinks rapidly form cell-laden hydrogels when exposed to UV light due to photoinduced thiol-ene crosslinking mechanism. Bioink viscosity and printability as well as bioprinted construct mechanics are controlled by bioink concentration and thiol to norbornene (T:NB) ratio. Human mesenchymal stem cells (hMSCs), NIH 3T3 fibroblasts, and human umbilical vein endothelial cells (HUVECs) are successfully bioprinted using our novel bioink formulations. Considering the high abundance, low cost, ability to selectively tether molecules or control crosslinking properties, norbornene modified cellulose-based bioink platforms have a significant potential to enable 3D bioprinted constructs with increased complexity.