Speakers - NWC 2023

Abstract

Peripheral nerve injury is a common clinical issue and challenge to human health that can result from natural disasters, industrial injuries, traffic jams, war wounds, and even some systemic diseases. Grafts such as acellular allogeneic or xenogeneic tissues and artificial conduits must often be implanted when the nerve lesion has a long gap or defect. Among various grafts, autografts are still regarded as the clinical gold standard to repair nerve injury. However, the limited sources of donor tissue, extra incisions, and the need to sacrifice normal nerve tissue, which leads to the risk of neuroma, limit the use of autografts. Thus, artificial nerve conduits were developed in the 1980s. Initially, these conduits were non-degradable, thereby inducing chronic inflammatory responses and leading to poor functional recovery in the regenerated nerve, often requiring a second surgery to remove these materials. Therefore, improvement using biodegradable materials has been carried out subsequently. Considering the unique properties of zein, such as its biocompatibility, biodegradability, and ease of fabrication, we report the use of zein conduits to repair injured rat sciatic nerves, firstly with a 10-mm defect rat model. Three-dimensional zein conduits were designed with/without pores, and with/without microtubes including in the lumen of conduits. Zein conduit with microtubes yielded satisfactory results in sciatic function index (SFI), proximal compound muscle action potentials, the density of myelinated nerve fibers, and myelin thickness, which were not inferior to autograft but slightly superior to the hollow conduit at the 4th-month post-implantation. The conduits degraded almost completely within two months, which was shorter than the suggested period of four months. Thus, the use of a porous conduit with microtubes inside as guidance may play important role in successful repair. Next, we challenged the repairment of the 15 mm defect rat model as it is much more difficult to regenerate than the 10 mm defect rat model when no addition of cells and growth factors. Considering the possible body's immune response to this plant protein material, we focused on the design of pore structured conduit and/or encapsulating an antiflammary drug dexamethasone. Zein triggered an early inflammatory response, but this response decreased to the level of the safe materials ALG and PLGA with degradation. Pore structure inhibited neutrophil recruitment and promoted macrophages polarizing towards the M2 phenotype. Thus, porous zein conduits with high and low porosity are further fabricated for the 15 mm sciatic nerve defect repair in rats. The conduits with high porosity induced more M2 macrophages to accelerate nerve regeneration with a shorter degradation period and better nerve repair efficacy.