Dexime: A Selectively Enzyme-Degradable Hydrogel for Protein Therapeutic Release

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Hydrogels are valuable for protein therapeutic delivery, avoiding harsh conditions.
• Dextrin, a biodegradable polysaccharide, has potential for hydrogel design but is underutilized.
• Click-crosslinking enables in situ gelation for injectable systems.

Purpose of the Study:

• To develop novel dextrin-based hydrogels (dexime) for injectable drug delivery.
• To investigate the tunable properties and degradation profiles of dexime hydrogels.
• To evaluate dexime hydrogels for the local delivery of chondroitinase ABC (ChASE) for CNS injury repair.

Main Methods:

• Dextrin was modified with ketone or aldehyde groups.
• Click-crosslinking with poly(ethylene glycol)-tetraoxyamine formed dextrin-oxime hydrogels.
• Rheological, mechanical, injectability, and degradation properties were assessed.
• Cytocompatibility and in vivo enzyme release were evaluated.

Main Results:

• Dexime hydrogels exhibited tunable rheological and mechanical properties based on formulation.
• Hydrogels were injectable through a 30G needle and selectively degraded by α-amylase.
• Dexime hydrogels showed stability in the presence of other enzymes and minimal swelling.
• In vitro and in vivo studies demonstrated successful delivery and activity of ChASE for scar degradation in the spinal cord.

Conclusions:

• Dexime hydrogels represent a promising, tunable, and injectable platform for localized therapeutic enzyme delivery.
• The selective degradation by α-amylase allows for controlled release in physiological environments.
• This system shows potential for treating central nervous system injuries by degrading scar tissue.