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An injectable PEG hydrogel controlling neurotrophin-3 release by affinity peptides
Jing Wang1, Richard Youngblood1, Luis Cassinotti2
1Department of Biomedical Engineering, University of Michigan, 48105 Ann Arbor, MI, USA.
Summary
This study developed an injectable hydrogel for sustained delivery of neurotrophin-3 to treat sensorineural hearing loss. The novel PEG hydrogel offers controlled release, improving upon existing methods for cochlear neuron survival.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Otolaryngology
Background:
- Sensorineural hearing loss is a significant health concern.
- Neurotrophin-3 (NT-3) shows potential for promoting cochlear neuron survival.
- Current delivery methods for therapeutic proteins to the inner ear face challenges in sustained and localized release.
Purpose of the Study:
- To develop an injectable hydrogel system for controlled and sustained localized delivery of neurotrophin-3.
- To create a delivery vehicle that enhances therapeutic protein residence time and efficacy for hearing loss treatment.
Main Methods:
- Formulation of a polyethylene glycol (PEG) hydrogel using thiol-vinyl sulfone Michael addition for crosslinking.
- Evaluation of hydrogel properties including mechanical rigidity, bio-adhesion, and residence time compared to Poloxamer hydrogels.
- Development of an affinity-based release system by conjugating NT-3 specific peptides to the PEG hydrogel.
- In vivo assessment of hydrogel biocompatibility and payload release kinetics.
Main Results:
- The developed PEG hydrogel formulation demonstrated superior mechanical rigidity, bio-adhesion, and residence time compared to Poloxamer hydrogels.
- PEG hydrogels exhibited comparable local immune responses to Poloxamer hydrogels but released payloads approximately 5-fold slower.
- The affinity-based system achieved sustained release of neurotrophin-3 through reversible peptide-protein interactions.
- Release rate was tunable based on polymer concentration, peptide affinity, and peptide-to-protein ratios.
Conclusions:
- An injectable PEG hydrogel system for localized, sustained delivery of neurotrophin-3 was successfully developed.
- This hydrogel platform offers an improved delivery mechanism for treating sensorineural hearing loss compared to current clinical approaches.
- The affinity-controlled release system provides a promising strategy for long-term therapeutic protein delivery in the ear.
