Injectable hydrogels for bone regeneration with tunable degradability via peptide chirality modification

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Hydrogel degradability is crucial for bone regeneration but poorly understood.
• Previous studies lacked sufficient variation in hydrogel degradation properties for comparison.

Purpose of the Study:

• To engineer matrix metalloproteinase (MMP)-responsive hydrogels with tunable degradation rates for bone regeneration.
• To investigate the impact of hydrogel degradation kinetics on bone repair processes.

Main Methods:

• Synthesized norbornene (NB)-modified 8-arm polyethylene glycol (PEG) macromers with MMP-sensitive peptides containing chirality-transferred amino acids.
• Tuned hydrogel degradation rates by altering peptide chirality (L, LD, D hydrogels).
• Evaluated hydrogel degradation in vitro and in vivo, assessing effects on cell migration and osteogenic gene expression.

Main Results:

• Developed MMP-responsive hydrogels with controllable degradation rates based on peptide chirality.
• The L-hydrogel variant exhibited significantly accelerated degradation in vitro and in vivo.
• Enhanced degradation of the L-hydrogel promoted cell migration and upregulated osteogenic gene expression, facilitating bone regeneration.

Conclusions:

• Hydrogel degradability is a fundamental factor influencing bone repair outcomes.
• Tunable degradation rates of MMP-responsive hydrogels offer a promising strategy for advancing bone regeneration therapies.
• This research provides insights for developing next-generation degradable biomaterials for bone tissue engineering.