A Combined Conduit-Bioactive Hydrogel Approach for Regeneration of Transected Sciatic Nerves

Transected peripheral nerve injury (PNI) affects the quality of life of patients, which leads to socioeconomic burden. Despite the existence of autografts and commercially available nerve guidance conduits (NGCs), the complexity of peripheral nerve regeneration requires further research in bioengine...

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Bibliographic Details
Published inACS applied bio materials Vol. 5; no. 10; pp. 4611 - 4624
Main Authors Lai, Cheuk Sun Edwin, Leyva-Aranda, Viridiana, Kong, Victoria H., Lopez-Silva, Tania L., Farsheed, Adam C., Cristobal, Carlo D., Swain, Joseph W. R., Lee, Hyun Kyoung, Hartgerink, Jeffrey D.
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 17.10.2022
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Summary:Transected peripheral nerve injury (PNI) affects the quality of life of patients, which leads to socioeconomic burden. Despite the existence of autografts and commercially available nerve guidance conduits (NGCs), the complexity of peripheral nerve regeneration requires further research in bioengineered NGCs to improve surgical outcomes. In this work, we introduce multidomain peptide (MDP) hydrogels, as intraluminal fillers, into electrospun poly­(ε-caprolactone) (PCL) conduits to bridge 10 mm rat sciatic nerve defects. The efficacy of treatment groups was evaluated by electro­myography and gait analysis to determine their electrical and motor recovery. We then studied the samples’ histo­morphometry with immuno­fluorescence staining and automatic axon counting/measurement software. Comparison with negative control group shows that PCL conduits filled with an anionic MDP may improve functional recovery 16 weeks postoperation, displaying higher amplitude of compound muscle action potential, greater gastrocnemius muscle weight retention, and earlier occurrence of flexion contracture. In contrast, PCL conduits filled with a cationic MDP showed the least degree of myelination and poor functional recovery. This phenomenon may be attributed to MDPs’ difference in degradation time. Electrospun PCL conduits filled with an anionic MDP may become an attractive tissue engineering strategy for treating transected PNI when supplemented with other bioactive modifications.
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Author Contributions
C.S.E.L., J.D.H., T.L.L.-S., and H.K.L. designed this study. C.S.E.L., V.L.-A., and V.H.K. synthesized and characterized the peptides. C.S.E.L. fabricated the conduits, performed surgeries, conducted gait analysis, and performed electromyography. V.L.-A., V.H.K., T.L.L.-S., A.C.F., and J.W.R.S. assisted in surgeries and electromyography. C.S.E.L. processed, imaged, and analyzed nerve tissues. C.S.E.L., V.H.K., C.D.C., and J.D.H. performed data processing. C.S.E.L., V.L.-A., V.H.K., and J.D.H. wrote the manuscript. J.D.H. supervised the entire study. All authors have read and approved the manuscript.
ISSN:2576-6422
2576-6422
DOI:10.1021/acsabm.2c00132