Tuning Superfast Curing Thiol‐Norbornene‐Functionalized Gelatin Hydrogels for 3D Bioprinting

Abstract

Photocurable gelatin-based hydrogels have established themselves as powerful bioinks in tissue engineering due to their excellent biocompatibility, biodegradability, light responsiveness, thermosensitivity and bioprinting properties. While gelatin methacryloyl (GelMA) has been the gold standard for many years, thiol-ene hydrogel systems based on norbornene-functionalized gelatin (GelNB) and a thiolated crosslinker have recently gained increasing importance. In this paper, a highly reproducible water-based synthesis of GelNB is presented, avoiding the use of dimethyl sulfoxide (DMSO) as organic solvent and covering a broad range of degrees of functionalization (DoF: 20% to 97%). Mixing with thiolated gelatin (GelS) results in the superfast curing photoclick hydrogel GelNB/GelS. Its superior properties over GelMA, such as substantially reduced amounts of photoinitiator (0.03% (w/v)), superfast curing (1-2 s), higher network homogeneity, post-polymerization functionalization ability, minimal cross-reactivity with cellular components, and improved biocompatibility of hydrogel precursors and degradation products lead to increased survival of primary cells in 3D bioprinting. Post-printing viability analysis revealed excellent survival rates of > 84% for GelNB/GelS bioinks of varying crosslinking density, while cell survival for GelMA bioinks is strongly dependent on the DoF. Hence, the semisynthetic and easily accessible GelNB/GelS hydrogel is a highly promising bioink for future medical applications and other light-based biofabrication techniques.

Bioinspired Multifunctional Black Phosphorus Hydrogel with Antibacterial and Antioxidant Properties: A Stepwise Countermeasure for Diabetic Skin Wound Healing

“…[ 34,35 ] It is a lightresponsive composite hydrogel with high porosity and predominant biocompatibility which were prepared by the method described in previous studies. [ 36,37 ]…”

“…[34,35] It is a lightresponsive composite hydrogel with high porosity and predominant biocompatibility which were prepared by the method described in previous studies. [36,37] In the gelatin process, shown in Figure 1H, the GelMA prepolymer was modified to a hydrogel via UV light at 365 nm for 30 Seconds. [38] The 4OI-BP@Gel can also easily form hydrogel under the same UV light.…”

Progress in Gelatin as Biomaterial for Tissue Engineering

“…The adding of methacrylol groups has resulted in important progress, but recent studies suggest a new trend in the use thiol-ene photocrosslinked hydrogels [64][65][66]. Unlike gelatin metachrylol, thiol-ene-and norbornene-modified gelatin hydrogels use a lower photoinitiator concentration.…”

“…Unlike gelatin metachrylol, thiol-ene-and norbornene-modified gelatin hydrogels use a lower photoinitiator concentration. Furthermore, norbornen's high selectivity towards thiols significantly improves cell survival [64]. One interesting example is the norbornene-and thiol-ene-based gelatin system designed by Göckler et al, which demonstrated a fast photocrosslinking process with barely any side reaction, and it enabled a cell survival rate above 80% regardless of the degree of cross-linking.…”

“…One interesting example is the norbornene-and thiol-ene-based gelatin system designed by Göckler et al, which demonstrated a fast photocrosslinking process with barely any side reaction, and it enabled a cell survival rate above 80% regardless of the degree of cross-linking. This is particularly important as methacrylate-gelatin-based hydrogels are totally dependent on the level of functionalization [64]. Another interesting approach is the fabrication of active gelatin scaffolds with tailored RGD motifs employing a site-specific enzymatic reaction.…”