G-2205

Fabrication of CNT–PCL/PLGA Nerve Conduit Filled with a Bioactive Hydrogel: A Novel Approach with Promising Features

 Alireza Bahrami Samani ¹, Fateme Karimzade ¹ ℗, Niloofar Nazeri ² ©   

 
Abstract

Introduction: Peripheral nerve injuries with critical-length gaps often struggle to restore full function due to insufficient axonal regrowth. Clinically, two main approaches exist for nerve reconstruction:autografts and synthetic nerve implants. While autografts remain the gold standard due to their native cellular and molecular composition, they are limited by donor site morbidity, additional iatrogenic trauma, and limited tissue availability.On the other hand, synthetic implants avoid these complications but often suffer from poor axonal guidance, limited growth factor content, and insufficient structural integrity. Furthermore, in both approaches mechanical weakness frequently prevents surgeons from applying secure sutures without risking damage or conduit collapse. To address these challenges we aim to pioneer a novel hybrid nerve guide, the ACRC (Aligned-core/random-cuff) conduit, which features a centrally aligned electrospun fiber core for directional neurite extension and randomly oriented cuffs for enhanced suture retention and improved structural integrity. Methods and Materials:Multiwalled Carbon nanotubes (CNTs) (0.25% w/v) were dispersed in hexafluoro‐2‐propanol (HFIP) and blended with poly(ε‐caprolactone) (PCL) and Poly(lactic-co-glycolic acid) (PLGA) to create an electrospinning solution.Using our novel airgap-modified electrospinning technique, fibers were electrospun into a conduit with a 16 mm length featuring a 10 mm aligned core and 3 mm random cuffs. The Au-ResNPs hydrogel prepared with collagen type I and stored in a sterile syringes. Both conduit and hydrogel characterized by SEM and TEM.Suture retention strength of conduit was measured, and PC12 cell viability was assessed on conduit segments with or without the hydrogel. In vivo, 20 male Wistar rats underwent unilateral transection of the sciatic nerve. They were divided into four groups: negative control, autograft, random-fiber CNT–PCL/PLGA conduit, and aligned-core/random-cuff (ACRC) CNT–PCL/PLGA conduit. All conduits were filled with 2 mL of a prepared hydrogel. Nerve segments and functional tests were harvested after 12 weeks for axon density, myelination, and functional recovery. (Ethical Code:IR.QUMS.REC.1402.036) Results: SEM revealed a more porous inner lumen and interwoven fibers on the outer surfaces with a parallel alignment in the central core. At the same time, TEM confirmed CNTs running along the fiber axes. The novel ACRC conduit demonstrated remarkable strength, withstanding a peak suture force of 3.3 N at 22.3 mm elongation, far exceeding the random-fiber conduit (3.2 N at 6.1 mm) and the fully aligned conduit (0.8 N at 3 mm). This superior mechanical robustness and suture retention, coupled with95% viability of PC12 cells after 7 days and the alignment of cells through the length of the conduit.In vivo, the ACRC group exhibited the highest axon density, significantly surpassing other groups. Functional assessments revealed improved hot-plate latencies, muscle volume, and compound action muscle potential in the ACRC group (P-value0.01). Conclusion: The ACRC conduit significantly enhanced axonal regeneration, mechanical strength, and functional recovery, offering a promising alternative to current research.

Keywords: Peripheral nerve injury (PNI); Nerve conduit; Electrospinning; Hydrogel; Nanomedicine