A Combined Conduit-Bioactive Hydrogel Approach for Regeneration of Transected Sciatic Nerves
Cheuk Sun Edwin Lai1, Viridiana Leyva-Aranda2, Victoria H Kong1
1Department of Bioengineering, Rice University, Houston, Texas 77005, United States.
ACS Applied Bio Materials
|April 21, 2022
Summary
Anionic multidomain peptide (MDP) hydrogels within poly(ε-caprolactone) (PCL) conduits improved functional recovery in peripheral nerve injury (PNI) models. This suggests PCL conduits with anionic MDPs are a promising strategy for nerve tissue engineering.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Neuroscience
Background:
- Peripheral nerve injury (PNI) significantly impacts patient quality of life and incurs socioeconomic costs.
- Current treatments like autografts and nerve guidance conduits (NGCs) have limitations, necessitating advancements in bioengineered solutions for nerve regeneration.
- Developing effective nerve guidance conduits is crucial for improving surgical outcomes in treating PNI.
Purpose of the Study:
- To investigate the efficacy of multidomain peptide (MDP) hydrogels as intraluminal fillers in electrospun poly(ε-caprolactone) (PCL) conduits for bridging peripheral nerve defects.
- To evaluate the functional, electrical, and motor recovery following PNI treatment using PCL conduits filled with anionic or cationic MDPs.
- To assess the histomorphometric changes and myelination status to understand the mechanisms underlying nerve regeneration.
Main Methods:
- Fabrication of electrospun PCL conduits and their intraluminal filling with anionic or cationic MDP hydrogels.
- Bridging a 10 mm rat sciatic nerve defect model with the prepared PCL conduits.
- Evaluation of functional recovery through electromyography and gait analysis, alongside histomorphometric analysis including immunofluorescence staining and automatic axon quantification.
Main Results:
- PCL conduits filled with anionic MDP demonstrated improved functional recovery 16 weeks postoperation compared to the negative control.
- Treatment with anionic MDP-filled conduits resulted in higher compound muscle action potential amplitude, better gastrocnemius muscle weight retention, and earlier flexion contracture.
- Conversely, PCL conduits filled with cationic MDP exhibited poor functional recovery and minimal myelination, potentially due to differences in degradation rates.
Conclusions:
- Electrospun PCL conduits incorporating anionic MDP hydrogels show potential as a viable tissue engineering strategy for treating transected peripheral nerve injuries.
- The differential degradation times of anionic and cationic MDPs may explain the observed variations in nerve regeneration and functional recovery.
- Supplementing PCL conduits with anionic MDPs, potentially with additional bioactive modifications, represents an attractive approach for enhancing peripheral nerve regeneration outcomes.
