Decellularized Biohybrid Nerve Promotes Motor Axon Projections

Abijeet Singh Mehta; Sophia L. Zhang; Xinran Xie; Shreyaa Khanna; Joshua Tropp; Xudong Ji; Rachel E. Daso; Colin K. Franz; Sumannas W. Jordan; Jonathan Rivnay

doi:10.1002/adhm.202401875

Decellularized Biohybrid Nerve Promotes Motor Axon Projections

Abijeet Singh Mehta, Sophia L. Zhang, Xinran Xie, Shreyaa Khanna, Joshua Tropp, Xudong Ji, Rachel E. Daso, Colin K. Franz, Sumannas W. Jordan, Jonathan Rivnay^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Developing nerve grafts with intact mesostructures, superior conductivity, minimal immunogenicity, and improved tissue integration is essential for the treatment and restoration of neurological dysfunctions. A key factor is promoting directed axon growth into the grafts. To achieve this, biohybrid nerves are developed using decellularized rat sciatic nerve modified by in situ polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT). Nine biohybrid nerves are compared with varying polymerization conditions and cycles, selecting the best candidate through material characterization. These results show that a 1:1 ratio of FeCl₃ oxidant to ethylenedioxythiophene (EDOT) monomer, cycled twice, provides superior conductivity (>0.2 mS cm⁻¹), mechanical alignment, intact mesostructures, and high compatibility with cells and blood. To test the biohybrid nerve's effectiveness in promoting motor axon growth, human Spinal Cord Spheroids (hSCSs) derived from HUES 3 Hb9:GFP cells are used, with motor axons labeled with green fluorescent protein (GFP). Seeding hSCS onto one end of the conduit allows motor axon outgrowth into the biohybrid nerve. The construct effectively promotes directed motor axon growth, which improves significantly after seeding the grafts with Schwann cells. This study presents a promising approach for reconstructing axonal tracts in humans.

Original language	English (US)
Article number	2401875
Journal	Advanced Healthcare Materials
Volume	13
Issue number	30
DOIs	https://doi.org/10.1002/adhm.202401875
State	Published - Dec 4 2024

Funding

A.S.M., C.K.F., and J.R. acknowledge funding from NSF ASCENT (NSF ECCS 2023849). J.T., R.D., and J.R. acknowledge support from the Office of Naval Research (ONR) Young Investigator Program (YIP) Award No. N00014-20-1-2777. C.K.F. acknowledges funding from the Belle Carnell Regenerative Neurorehabilitation. This work utilized the Analytical bioNanoTechnology Equipment Core (ANTEC) and the Center for Advanced Microscopy/Nikon Imaging Center (CAM). Imaging work was also performed at the Northwestern University Center for Advanced Microscopy generously supported by CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. This work also utilized the Keck-II facility of Northwestern University's NUANCE Center and the Northwestern University Micro/Nano Fabrication Facility (NUFAB), both of which receive partial support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633), the Materials Research Science and Engineering Center (NSF DMR-2308691), the State of Illinois, and Northwestern University. Additionally, the Keck-II facility is partially supported by the International Institute for Nanotechnology (IIN), the Keck Foundation, and the State of Illinois, through the IIN. A.S.M., C.K.F., and J.R. acknowledge funding from NSF ASCENT (NSF ECCS 2023849). J.T., R.D., and J.R. acknowledge support from the Office of Naval Research (ONR) Young Investigator Program (YIP) Award No. N00014\u201020\u20101\u20102777. C.K.F. acknowledges funding from the Belle Carnell Regenerative Neurorehabilitation. This work utilized the Analytical bioNanoTechnology Equipment Core (ANTEC) and the Center for Advanced Microscopy/Nikon Imaging Center (CAM). Imaging work was also performed at the Northwestern University Center for Advanced Microscopy generously supported by CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. This work also utilized the Keck\u2010II facility of Northwestern University's NUANCE Center and the Northwestern University Micro/Nano Fabrication Facility (NUFAB), both of which receive partial support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS\u20102025633), the Materials Research Science and Engineering Center (NSF DMR\u20102308691), the State of Illinois, and Northwestern University. Additionally, the Keck\u2010II facility is partially supported by the International Institute for Nanotechnology (IIN), the Keck Foundation, and the State of Illinois, through the IIN.

Keywords

bioelectronics
conducting polymers
motor axons
pedot
spinal spheroids

ASJC Scopus subject areas

Biomaterials
Biomedical Engineering
Pharmaceutical Science

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10.1002/adhm.202401875

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abstract = "Developing nerve grafts with intact mesostructures, superior conductivity, minimal immunogenicity, and improved tissue integration is essential for the treatment and restoration of neurological dysfunctions. A key factor is promoting directed axon growth into the grafts. To achieve this, biohybrid nerves are developed using decellularized rat sciatic nerve modified by in situ polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT). Nine biohybrid nerves are compared with varying polymerization conditions and cycles, selecting the best candidate through material characterization. These results show that a 1:1 ratio of FeCl3 oxidant to ethylenedioxythiophene (EDOT) monomer, cycled twice, provides superior conductivity (>0.2 mS cm−1), mechanical alignment, intact mesostructures, and high compatibility with cells and blood. To test the biohybrid nerve's effectiveness in promoting motor axon growth, human Spinal Cord Spheroids (hSCSs) derived from HUES 3 Hb9:GFP cells are used, with motor axons labeled with green fluorescent protein (GFP). Seeding hSCS onto one end of the conduit allows motor axon outgrowth into the biohybrid nerve. The construct effectively promotes directed motor axon growth, which improves significantly after seeding the grafts with Schwann cells. This study presents a promising approach for reconstructing axonal tracts in humans.",

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AU - Ji, Xudong

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AU - Jordan, Sumannas W.

AU - Rivnay, Jonathan

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Decellularized Biohybrid Nerve Promotes Motor Axon Projections

Abstract

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Keywords

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