<b>Microwave-Assisted Aqueous synthesis of Norbornene-functionalized macromers for hydrogel crosslinking</b>

<p dir="ltr">Radical initiated thiol-norbornene (thiol-ene) click chemistry has been widely used in fabricating hydrogels for biomedical applications owing to its efficiency, modularity, and cytocompatibility. However, previously reported methods of norbornene conjugation to natural and synthetic polymers require long reaction times and large quantities of various organic solvents. Improving norbornene conjugation efficiency could allow greater adoption of this chemistry for hydrogel synthesis. To this end, microwave-assisted synthesis can accelerate reactions while maintaining consistency. The current microwave-assisted methods for synthesizing macromers for hydrogel crosslinking are limited and this work demonstrates the adaptation of norbornene conjugation methods to a microwave reactor for rapid synthesis of highly substituted macromers. Conjugation of norbornene to multi-arm poly(ethylene glycol)-amine using microwave methods reduced reaction time from 48 hours to 90 minutes while improving the conversion from 83.1% to 98.3%. Macromers with higher conversion produced hydrogels with increased elastic moduli (G’). On the other hand, microwave-assisted synthesis of gelatin norbornene (μwGelNB) provided a robust and efficient synthesis route, where norbornene substitution was controlled from ~60-90% by adjusting reaction time between 7.5 and 45 minutes. Longer microwave heating rendered the gelatin less viscous while increased functionalization, allowing hydrogel fabrication with higher G’ than conventionally synthesized material. Additionally, μwGelNB was used to fabricate small positive and negative architectures using a digital light processing (DLP) bioprinter. Lastly, compared with conventional GelNB, μwGelNB hydrogels supported superior endothelial cell network formation</p>