Poly(ethylene glycol)–Norbornene as a Photoclick Bioink for Digital Light Processing 3D Bioprinting

Abstract

Digital light processing (DLP) bioprinting is an emerging technology for three-dimensional bioprinting (3DBP) owing to its high printing fidelity, fast fabrication speed, and higher printing resolution. Low-viscosity bioinks such as poly(ethylene glycol) diacrylate (PEGDA) are commonly used for DLP-based bioprinting. However, the cross-linking of PEGDA proceeds via chain-growth photopolymerization that displays significant heterogeneity in cross-linking density. In contrast, step-growth thiol–norbornene photopolymerization is not oxygen inhibited and produces hydrogels with an ideal network structure. The high cytocompatibility and rapid gelation of thiol–norbornene photopolymerization have lent itself to the cross-linking of cell-laden hydrogels but have not been extensively used for DLP bioprinting. In this study, we explored eight-arm PEG–norbornene (PEG8NB) as a bioink/resin for visible light-initiated DLP-based 3DBP. The PEG8NB-based DLP resin showed high printing fidelity and cytocompatibility even without the use of any bioactive motifs and high initial stiffness. In addition, we demonstrated the versatility of the PEGNB resin by printing solid structures as cell culture devices, hollow channels for endothelialization, and microwells for generating cell spheroids. This work not only expands the selection of bioinks for DLP-based 3DBP but also provides a platform for dynamic modification of the bioprinted constructs.

Transformative Materials to Create 3D Functional Human Tissue Models In Vitro in a Reproducible Manner

“…Therefore, synthetic bioinks are under development to overcome these limitations. For example, PEG‐based bioinks that crosslink via photopolymerization [ 180 ] or Michael‐type addition [ 181 ] are printed into complex shapes that can be biofunctionalized to support cell culture.…”

Digital Light Processing 3D Bioprinting of Gelatin‐Norbornene Hydrogel for Enhanced Vascularization

“…Increasingly, GelNB has been used in 3D bioprinting space. [8,36,37] For example, Soliman et al used Gel-NOR (same as our GelNB) as a bioink for DLP bioprinting, [38] where the cross-linking was initiated by a ruthenium/sodium persulfate (Ru/SPS) photoinitiating system. While this work presented convincing evidence that DLP-printed GelNB hydrogels support vascular network formation, no postgelation modification of DLP-printed hydrogel was conducted.…”

“…[3] A variety of approaches have been developed to fabricate vascularized 3D constructs, including endothelial cells-laden bioactive and degradable hydrogels, [4,5] porous polymeric scaffolds, [6,7] and matrices/scaffolds with perfusable channels. [8][9][10] 3D bioprinting techniques, including extrusion-based bioprinting, digital light processing (DLP), and tomographic light projections (volumetric) bioprinting, are particularly useful in creating complex 3D scaffolds with embedded perfusable channels. Among these biofabrication techniques, DLP bioprinting is an attractive platform for rapidly creating 3D cell-laden constructs with biologically relevant resolution and structural complexity.…”

“…[ 24,25 ] For example, our group has previously reported the development of synthetic 8‐arm PEG‐norbornene (PEGNB) as a bioink for DLP bioprinting. [ 8 ] Various 3D structures, including perfusable channels, were printed with high printing fidelity. We also demonstrated that the DLP‐printed bioinert PEGNB hydrogels could be conjugated with cell‐adhesive peptide (e.g., CRGDS) post‐printing to increase cell attachment on the surface of the hydrogels.…”

Trends in Photopolymerizable Bioinks for 3D Bioprinting of Tumor Models

“…The utility of PBs in vat-based bioprinting involving biomaterials such as alginate, gelatin, and hyaluronic acid can avoid filler materials such as rheological modifiers needed in extrusion-based bioprinting to render them printable and minimize undesired cellular response . We and others have introduced novel and improved polymeric bioink formulations for vat-based bioprinting for various tissue engineering applications. − Even though certain limitations exist, such as cellular-level toxicity due to exposure to far ultraviolet (UV) light and free radicals produced by PI and unreacted polymers, exist. These can be minimized by using optimal concentrations of the polymers and PIs with visible light sensitivity to avoid genetic alterations …”