Evaluation of peripheral nerve regeneration through biomaterial conduits via micro‐CT imaging

Abstract

ObjectiveHollow nerve conduits made of natural or synthetic biomaterials are used clinically to aid regeneration of peripheral nerves damaged by trauma or disease. To support healing, conduit lumen patency must be maintained until recovery occurs. New methods to study conduit structural integrity would provide an important means to optimize conduits in preclinical studies. We explored a novel combined technique to examine structural integrity of two types of nerve conduits after in vivo healing.Study DesignMicro‐CT imaging with iodine contrast was combined with histological analysis to examine two different nerve conduits after in vivo nerve reconstruction in rats.Materials and MethodsSciatic nerve gaps in adult Lewis rats were reconstructed with poly(caprolactone) (PCL, 1.6 cm gap, 14‐week survival) or silicone (1 cm gap, 6‐week survival) conduits (N = 12 total). Conduits with regenerating tissues were imaged by micro‐CT with iodine contrast and compared to the histology (hematoxylin and eosin, immunostaining for axons) of regenerated tissues after iodine removal.ResultsPCL nerve conduits showed extensive breakage throughout their length, but all showed successful nerve growth through the conduits. The silicone conduits remained intact, although significant constriction was uniquely detected by micro‐CT, with 1 of 6 animals showing incomplete tissue regeneration.ConclusionsMicro‐CT with iodine contrast offers a unique and valuable means to determine 3D structural integrity of nerve conduits and nerve healing following reconstruction. Furthermore, this paper shows that even if conduit compression and degradation occur, nerve regeneration can still take place.

Biomimetic neural scaffolds: a crucial step towards optimal peripheral nerve regeneration

“…35 The association between increased conduit wall thickness and decreased nerve regeneration is likely mediated by decreased nutrient diffusion and wall porosity. 36 In vitro , it has been shown using a material degradation and diffusion study that the optimal conditions for peripheral nerve repair are achieved with a conduit wall thickness of 0.6 mm, a porosity of 80%, and a pore size range of ~10–40 µm. 37 In a rodent model, it has also been shown that biodegradable nerve guides optimally aid nerve regeneration when featuring an internal diameter of 1.5 mm and a wall thickness of 0.3 mm.…”

Smart Hydrogels in Tissue Engineering and Regenerative Medicine

“…This application of hydrogels in skin tissue engineering has been mainly developed because of the drawbacks associated with the use of autografts and allografts where the donor site suffers from pain, recurrent infections, scarring over a while. Tissue-engineered skin replacements have found widespread applications in wound healing, especially in the case of burns, where the major limiting factor is the availability of autologous skin [131,132].…”

The advances in nerve tissue engineering: From fabrication of nerve conduit toin vivonerve regeneration assays

“…Also, it has been shown that a PCL conduit can improve motor functional recovery by increase in sciatic functional index (SFI) values, recovery in muscle atrophy, and increase in number of regenerated axons in the sciatic nerve gaps due to creating proper porosity and increase of vascularization in the implanted site (Pixley et al, ; Zhu et al, ). Therefore, this polymer can be considered as one of the most suitable candidates for fabricating the neural conduit.…”