Decellularized Biohybrid Nerve Promotes Motor Axon Projections

• Published in: Advanced healthcare materials 2024-12, Vol.13 (30), p.e2401875-n/a
• Main Authors: Mehta, Abijeet Singh, Zhang, Sophia L., Xie, Xinran, Khanna, Shreyaa, Tropp, Joshua, Ji, Xudong, Daso, Rachel E., Franz, Colin K., Jordan, Sumannas W., Rivnay, Jonathan
• Format: Article
• Language: English
• Subjects: Alignment; Allografts; Animals; Axonogenesis; Axons; Axons - metabolism; Axons - physiology; bioelectronics; Bridged Bicyclo Compounds, Heterocyclic - chemistry; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; conducting polymers; Cycle ratio; Ferric chloride; Fluorescence; Grafting; Grafts; Green fluorescent protein; Humans; Immunogenicity; motor axons; Motor Neurons; Nerve Regeneration - physiology; Nerves; Neurological diseases; Oxidants; Oxidizing agents; pedot; Polymerization; Polymers - chemistry; Protein seeding; Rats; Rats, Sprague-Dawley; Schwann cells; Sciatic nerve; Sciatic Nerve - physiology; Spheroids; Spheroids, Cellular - cytology; Spinal cord; Spinal Cord - physiology; spinal spheroids; Tissue Engineering - methods; Tissue Scaffolds - chemistry
• ISSN: 2192-2640; 2192-2659; 2192-2659
• DOI: 10.1002/adhm.202401875

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. Developing nerve grafts promoting axonal ingrowth is vital for treating neurological dysfunctions. This study creates biohybrid nerves using decellularized rat sciatic nerve modified with PEDOT. These biohybrid nerves effectively promote motor axon ingrowth, especially when seeded with Schwann cells, showing promise for human axonal tract reconstruction.