Hydrolytically Degradable PEG-Based Inverse Electron Demand Diels-Alder Click Hydrogels

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Chemical Engineering

Background:

• Inverse electron demand Diels-Alder (iEDDA) click chemistry is widely used for hydrogel formation in biomedical applications.
• Existing synthetic iEDDA hydrogels lack tunable and accelerated hydrolytic degradation, limiting their utility.
• Previously developed norbornene (NB)-functionalized poly(ethylene glycol) (PEG) macromers with carbic anhydride (CA) showed tunable degradation.

Purpose of the Study:

• To develop the first synthetic iEDDA click hydrogels with tunable hydrolytic degradation kinetics.
• To investigate the use of PEGNB_CA macromers in iEDDA hydrogel formation.
• To assess the cytocompatibility and biocompatibility of these novel hydrogels.

Main Methods:

• Synthesized PEGNB_CA macromers for iEDDA click hydrogel formation.
• Utilized [methyl]tetrazine ([m]Tz)-modified macromers for cross-linking.
• Exploited dual conjugation of tetrazine (Tz) and mTz for degradation control.
• Evaluated in vitro degradation kinetics and cytocompatibility.
• Assessed in vivo biocompatibility.

Main Results:

• Developed the first synthetic iEDDA click hydrogels exhibiting highly tunable hydrolytic degradation.
• Achieved degradation times ranging from 2 weeks to 3 months by exploiting dual Tz and mTz conjugation.
• Demonstrated excellent in vitro cytocompatibility.
• Confirmed excellent in vivo biocompatibility of the injectable hydrogels.

Conclusions:

• PEGNB_CA-based iEDDA click hydrogels offer a novel platform for tunable degradation in biomedical applications.
• The developed hydrogels exhibit a wide range of controllable degradation rates.
• These injectable hydrogels show promising biocompatibility for in vivo use.