Evaluation of enzymatically crosslinked injectable glycol chitosan hydrogel

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Glycol chitosan is a biocompatible polymer with potential for biomedical applications.
• Developing injectable and cross-linkable hydrogels is crucial for effective drug delivery and tissue regeneration.
• Enhancing the osteoinductivity of biomaterials can accelerate bone healing processes.

Purpose of the Study:

• To synthesize and characterize enzymatically cross-linkable phenol-conjugated glycol chitosan hydrogels.
• To evaluate the hydrogel's potential for controlled release of recombinant human bone morphogenetic protein-2 (rhBMP-2).
• To assess the in vivo osteoinductivity and bone regeneration capacity of the rhBMP-2 loaded hydrogel in a calvarial defect model.

Main Methods:

• Glycol chitosan was conjugated with 3-(4-hydroxyphenyl)propionic acid (HPP).
• Hydrogels (HPP-GC) were formed via enzymatic oxidative coupling of phenol groups.
• Characterization included rheology, porosity, and in vitro release studies.
• In vivo efficacy was tested using a critical size calvarial bone defect in mice, assessing mineralization and defect closure.

Main Results:

• Successful synthesis and confirmation of phenol-conjugated glycol chitosan.
• HPP-GC hydrogels exhibited tunable rheological properties and a microporous structure.
• Non-toxicity of gelation conditions was confirmed by osteoblast viability.
• In vitro release of rhBMP-2 was sustained over 360 hours (∼11%).
• In vivo studies demonstrated active mineralization, remodeling, and complete defect closure within 8 weeks.

Conclusions:

• Phenol-conjugated glycol chitosan hydrogels are a promising platform for rhBMP-2 delivery.
• The hydrogel system supports cell viability and promotes significant bone regeneration.
• These findings highlight the potential of HPP-GC hydrogels for enhancing osteoinductivity in bone defect repair.