Degradation characteristics and biotoxicity of new domestic polyglycolic acid neural catheter

Abstract

BACKGROUND: Neural catheterization repair of peripheral nerve defects is a research hotspot in the field of biomedical engineering, but the autologous nerve graft repair method as the gold standard has limitations, so there is an urgent need for a method that can replace autologous nerve grafting to repair peripheral nerve defects. OBJECTIVE: To observe the degradation characteristics and biological toxicity of the new domestic polyglycolic acid neural catheters. METHODS: (1) Degradation performance: PBS was added to the test tubes of the blank control group. PBS and new domestic polyglycolic acid neural catheter were added to the test tubes of the fluid exchange group, with PBS changed every 3 days. PBS and the new domestic polyglycolic acid neural catheter were added to the test tubes of the non-fluid exchange group, without changing the fluid. All three groups of test tubes were placed in a 37℃ incubator, and the pH value of the liquid in each test tube was measured weekly. (2) Cell experiment: Human fibroblasts were divided into two groups: the control group was added with pure medium, and the experimental group was added with medium containing the extract of the new domestic polyglycolic acid neural catheter. The cytocompatibility of the neural catheter was evaluated by cell morphology, CCK-8 assay, scratch test, and Transwell assay. (3) In vivo histocompatibility: The new domestic polyglycolic acid neural catheter and an imported neural catheter were implanted between the biceps femoris and gluteus maximus muscles of SD rats to evaluate the degradation characteristics and biotoxicity of the neural catheters. RESULTS AND CONCLUSION: (1) In vitro degradation experiments showed that under fluid exchange conditions, the degradation of the new domestic polyglycolic acid neural catheter had little effect on the pH value of the surrounding fluid; under non-fluid exchange conditions, the degradation of the new domestic polyglycolic acid neural catheter could reduce the pH value of the surrounding fluid. (2) The growth state of cells in both groups was good, and the cell morphology and volume were normal. CCK-8 assay showed that the new domestic polyglycolic acid neural catheter did not affect the proliferation of human fibroblasts. Scratch test and Transwell assay showed that the new domestic polyglycolic acid neural catheter did not affect the migration of human fibroblasts. (3) The degradation of the new domestic polyglycolic acid neural catheter was similar to that of the imported neural catheter. Hematoxylin-eosin staining showed that the new domestic polyglycolic acid neural catheter had no obvious effect on the main organs of rats. Masson staining showed that the tissue around the neural catheter in both groups was normal, and no inflammatory cell infiltration was observed. (4) The results indicate that the new domestic polyglycolic acid neural catheter has good degradability and no biotoxicity.

1. Introduction

Peripheral nerve defects are a significant clinical condition [1-2], often caused by crush injuries, blast injuries, and lacerations [3-4], leading to motor and sensory loss. Due to the high degree of differentiation and stability of nerve cells, if not treated promptly, regeneration is typically slow and functional recovery incomplete, potentially resulting in permanent loss of function [5-6]. Therefore, nerve grafts are required to repair nerve defects that cannot be directly sutured. Currently, autologous nerve grafting remains the gold standard for treating peripheral nerve defects [7-8], but this method has limitations such as poor donor site wound healing, dysfunction, neuroma formation, and size/structure mismatch [9]. In contrast, artificial biodegradable nerve conduits can avoid these limitations [10-11].

Polyglycolic acid (PGA) is one of the commonly used materials for fabricating nerve conduits, with degradation products of CO2 and H2O [12]. PGA possesses three key characteristics: biodegradability, porosity, and flexibility [13]. Biodegradability eliminates the need for a second surgery, porosity facilitates material exchange between tissue and the environment, and flexibility allows the conduit to not impede limb movement. Additionally, PGA provides good mechanical integrity, ensuring the product does not undergo structural fracture or length reduction during in vivo degradation [14]. In 1999, the first nerve conduit approved for clinical use was made of PGA, produced by Synovis Micro as Neurotube®, which has been approved by the FDA [15]. This product is currently the main nerve conduit used clinically in China, but it is expensive. If the new domestic PGA neural catheter exhibits comparable performance to Neurotube®, it could be applied clinically, reducing the economic burden on patients and allowing for further improvements and innovations. This study conducted a series of experiments on the new domestic PGA neural catheter to observe its degradation characteristics and biotoxicity.