Optimized Photoclick (Bio)Resins for Fast Volumetric Bioprinting

Abstract

Volumetric printing (VP) is a light‐mediated technique enabling printing of complex, low‐defect 3D objects within seconds, overcoming major drawbacks of layer‐by‐layer additive manufacturing. An optimized photoresin is presented for VP in the presence of cells (volumetric bioprinting) based on fast thiol–ene step‐growth photoclick crosslinking. Gelatin‐norbornene (Gel‐NB) photoresin shows superior performance, both in physicochemical and biocompatibility aspects, compared to (meth‐)acryloyl resins. The extremely efficient thiol–norbornene reaction produces the fastest VP reported to date (≈10 s), with significantly lower polymer content, degree of substitution (DS), and radical species, making it more suitable for cell encapsulation. This approach enables the generation of cellular free‐form constructs with excellent cell viability (≈100%) and tissue maturation potential, demonstrated by development of contractile myotubes. Varying the DS, polymer content, thiol–ene ratio, and thiolated crosslinker allows fine‐tuning of mechanical properties over a broad stiffness range (≈40 Pa to ≈15 kPa). These properties are achieved through fast and scalable methods for producing Gel‐NB with inexpensive, off‐the‐shelf reagents that can help establish it as the gold standard for light‐mediated biofabrication techniques. With potential applications from high‐throughput bioprinting of tissue models to soft robotics and regenerative medicine, this work paves the way for exploitation of VPs unprecedented capabilities.

Volumetric Bioprinting of Organoids and Optically Tuned Hydrogels to Build Liver‐Like Metabolic Biofactories

“…This specific size was selected to generate filaments that could completely embed the produced organoids, even though finer printing resolution are possible as shown before in Figure 1B,C, in which resolution superior to what is shown with volumetric printing up to date has been demonstrated. [15,16,24,25] In an ideal print, both the thick border of the disc and the thinner filament, herein used as a benchmark to quantify the printing resolution, should solidify at the same time after receiving the same, optimal light dose. Exceeding this optimal dose will cause overcuring of the fine feature, thickening of the filament wall, and eventually clogging of the disc.…”

Stem Cell-Laden Hydrogel-Based 3D Bioprinting for Bone and Cartilage Tissue Engineering

“…For example, biphasic calcium phosphate (BCP) and matrigel/alginate hydrogel composites were synthesized by EBB to induce osteogenesis of incorporated MSCs as an osteoinductive bone filler at the area of bone defects ( Fedorovich et al, 2011 ). In addition, volumetric 3D bioprinting is a light-mediated technique, which enables excellent cell viability, structural fidelity, and tissue maturation potential ( Rizzo et al, 2021 ). It has been reported that volumetric tomographic bioprinting of a bone model could promote osteocytic differentiation, which would be a powerful tool for biofabrication of 3D bone-like tissues ( Gehlen et al, 2021 ).…”

Next Evolution in Organ‐Scale Biofabrication: Bioresin Design for Rapid High‐Resolution Vat Polymerization

“…Interestingly, there was a need for postprinting processing when GelMA was used as the bioresin for volumetric tomographic printing, where the printed constructs were further immersed into a secondary photoinitiator bath, followed by additional photoirradiation. By contrast, a recent publication by Rizzo et al [200] showed that when gelatin-norbornene (GelNB) was used for volumetric tomographic printing, there was no need for postprinting crosslinking. Although both GelMA and Reproduced with permission.…”