3D Printed Conductive Multiscale Nerve Guidance Conduit with Hierarchical Fibers for Peripheral Nerve Regeneration

Abstract

Nerve guidance conduits (NGCs) have become a promising alternative for peripheral nerve regeneration; however, the outcome of nerve regeneration and functional recovery is greatly affected by the physical, chemical, and electrical properties of NGCs. In this study, a conductive multiscale filled NGC (MF-NGC) consisting of electrospun poly(lactide-co-caprolactone) (PCL)/collagen nanofibers as the sheath, reduced graphene oxide /PCL microfibers as the backbone, and PCL microfibers as the internal structure for peripheral nerve regeneration is developed. The printed MF-NGCs presented good permeability, mechanical stability, and electrical conductivity, which further promoted the elongation and growth of Schwann cells and neurite outgrowth of PC12 neuronal cells. Animal studies using a rat sciatic nerve injury model reveal that the MF-NGCs promote neovascularization and M2 transition through the rapid recruitment of vascular cells and macrophages. Histological and functional assessments of the regenerated nerves confirm that the conductive MF-NGCs significantly enhance peripheral nerve regeneration, as indicated by improved axon myelination, muscle weight increase, and sciatic nerve function index. This study demonstrates the feasibility of using 3D-printed conductive MF-NGCs with hierarchically oriented fibers as functional conduits that can significantly enhance peripheral nerve regeneration.

An Adaptable Drug Delivery System Facilitates Peripheral Nerve Repair by Remodeling the Microenvironment

“…The commonly recognized designs within nerve guides include hollow architectures, groove formations, multichannel arrangements, and internally filled structures utilizing fibers, sponges, hydrogels, − etc. The hydrogel, which emulates the extracellular matrix, exhibits high water content, creates a three-dimensional (3D) microenvironment for cellular activities, and allows for the incorporation of chemical molecules.…”

Developing conductive hydrogels for biomedical applications

“…114 It was reported that a conductive multiscale NGC (MF-NGC) had a positive effect on neurite outgrowth of neuronal cells, and hierarchically arranged fibers promoted the regeneration of peripheral nerve tissues (Figure 7A). 115 In contrast, electrical stimulation has demonstrated to enhance cell proliferation and growth. Jiang et al fabricated a conductive composite conduit with alignment structure for nerve regeneration.…”

“…(iii) H&E staining. Source: Reproduced under terms of the CC-BY license 115. Copyright 2023, The Authors, published by John Wiley and Sons.…”

Advancing Peripheral Nerve Regeneration: 3D Bioprinting of GelMA-Based Cell-Laden Electroactive Bioinks for Nerve Conduits

“…Despite the occurrence of direct-current electric fields in developing and regenerating nerve tissue, the potential significance of these electric fields has been largely overlooked in many of the hydrogel-based nerve regeneration reports. , Nevertheless, some studies have highlighted the significance of the bioink’s electroactivity as the key factor in developing NGC-specific bioinks for bioprinting purposes. , An electrically conductive hydrogel was developed by incorporating reduced graphene oxide (rGO) into GelMA for the production of NGCs . The composite bioink (GelMA/rGO) demonstrated enhanced neuritogenesis of PC12 cells in vitro and significantly enhanced sciatic nerve regeneration in rat models, compared to the pure GelMA due to the improved conductivity.…”