Injectable and redox-responsive hydrogel with adaptive degradation rate for bone regeneration

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Polymer Chemistry

Background:

• Hydrogels are crucial for tissue regeneration, but controlling their degradation and release profiles remains challenging.
• Injectable scaffolds offer minimally invasive delivery for tissue engineering applications.

Purpose of the Study:

• To develop an in situ crosslinkable poly(ethylene glycol) (PEG) hydrogel with adaptive degradation for tissue regeneration.
• To investigate the hydrogel's properties, including gelation, degradation kinetics, and cell interactions.
• To evaluate the hydrogel's potential for delivering osteoinductive growth factors for bone formation.

Main Methods:

• Synthesized thiolated PEG precursors for rapid hydrogel formation via oxidation.
• Controlled gelation time and storage modulus by adjusting precursor concentrations.
• Modulated degradation and protein release by varying reduced glutathione (GSH) concentration.
• Assessed cell spreading and migration within the hydrogel.
• Loaded recombinant human bone morphogenetic protein-2 (rhBMP-2) for ectopic bone formation studies.

Main Results:

• Achieved rapid in situ gelation under physiological conditions with tunable mechanical properties.
• Demonstrated redox-responsive degradation, allowing modulation of degradation time from 2 to 32 days.
• Showcased controlled protein release kinetics synchronized with degradation.
• Observed significant cell spreading and migration within the hydrogel matrix.
• Successfully induced ectopic bone formation via rhBMP-2 delivery, correlating with gel degradation.

Conclusions:

• Developed a disulfide-crosslinked hydrogel with tunable, redox-responsive gelation and degradation.
• The injectable hydrogel supports cell infiltration and controlled release of therapeutic proteins.
• This advanced hydrogel carrier shows significant promise for non-invasive tissue regeneration and cytokine delivery strategies.