Abstract
Nerve guidance conduits (NGCs) are tubular scaffolds that act as a bridge between the proximal and distal ends of the native nerve to facilitate the nerve regeneration. The application of NGCs is mostly limited to nerve defects less than 3 mm due to the lack of sufficient cells in the lumen. The development of drug-release-system-embedded NGCs has the potential to improve the nerve regeneration performance by providing long-term release of growth factors. However, most of the past works only focused on one type of drug release system, limiting the variation in drug release system types and features. Therefore, in this study, computer-aided design (CAD) models were constructed and Computational Fluid Dynamics (CFD) simulations were carried out to investigate the effect of growth factor transporting efficiency on different drug release systems. To overcome the challenges posed by the current NGCs in treating long nerve gap injuries (>4 cm), a novel ‘relay’ NGC design is first proposed in this paper and has the potential to improve the nerve regeneration performance to next level. The intermediate cavities introduced along the length of the multi-channel NGCs act as a relay to further enhance the cell concentrations or growth factor delivery as well as the regeneration performance. Four different drug release systems, namely, a single-layer microsphere system, a double-layer microsphere system, bulk hydrogel, and hydrogel film, were chosen for the simulation. The results show that the double-layer microsphere system achieves the highest growth factor volume fraction among all the drug release systems. For the single-layer microsphere system, growth factor concentration can be significantly improved by increasing the microsphere quantities and decreasing the diameter and adjacent distance of microspheres. Bulk hydrogel systems hold the lowest growth factor release performance, and the growth factor concentration monotonically increased with the increase of film thickness in the hydrogel film system. Owing to the easy fabrication of hydrogel film and the even distribution of growth factors, the hydrogel film system can be regarded as a strong candidate in drug-eluting NGCs. The use of computational simulations can be regarded as a guideline for the design and application of drug release systems, as well as a promising tool for further nerve tissue engineering study.
Highlights
IntroductionPeripheral nerve injuries can result from either systemic disease (e.g., diabetes, Guilain–Barre syndrome, carpal tunnel syndrome) or localized damage (e.g., trauma, sports-related stretching/compression, tumor extirpation)
Peripheral nerve injuries can result from either systemic disease or localized damage
Autograft suffers from donor site morbidity, considering its excellent regeneration performance, it remains the first choice for long-gap nerve injuries (>4 cm) and is treated as the gold standard among all the clinical methods [6]
Summary
Peripheral nerve injuries can result from either systemic disease (e.g., diabetes, Guilain–Barre syndrome, carpal tunnel syndrome) or localized damage (e.g., trauma, sports-related stretching/compression, tumor extirpation). Peripheral nerve injuries can be classified into five stages with increasing severity, starting from a self-restorable local conduction block to a complete transection of the nerve. It is hard for the nerve to self-regenerate when it experiences a complete transection; an external treatment is required to promote the nerve regeneration. Pharmaceutics 2022, 14, 230 groups: direct coaptation, grafts, and nerve guidance conduits (NGC). Grafts are more suitable for long-gap nerve injuries rather than direct coaptation. Autograft involves harvesting a section of the nerve from the patient and transplanting it directly to the injury site. Autograft suffers from donor site morbidity, considering its excellent regeneration performance, it remains the first choice for long-gap nerve injuries (>4 cm) and is treated as the gold standard among all the clinical methods [6]
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