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Objective To analyze the characteristics of menicus microstructure and to reconstruct a microstructure‐mimicing 3D model of the menicus. Methods Human and sheep meniscus were collected and prepared for this study. Hematoxylin–eosin staining (HE) and Masson staining were conducted for histological analysis of the meniscus. For submicroscopic structure analysis, the meniscus was first freeze‐dried and then scanned by scanning electron microscopy (SEM). The porosity of the meniscus was determined according to SEM images. A micro‐MRI was used to scan each meniscus, immersed in distilled water, and a 3D digital model was reconstructed afterwards. A three‐dimensional (3D) resin model was printed out based on the digital model. Before high‐resolution micro‐CT scanning, each meniscus was freeze‐dried. Then, micro‐scale two‐dimensional (2D) CT projection images were obtained. The porosity of the meniscus was calculated according to micro‐CT images. With micro‐CT, multiple 2D projection images were collected. A 3D digital model based on 2D CT pictures was also reconstructed. The 3D digital model was exported as STL format. A 3D resin model was printed by 3D printer based on the 3D digital model. Results As revealed in the HE and Masson images, a meniscus is mostly composed of collagen, with a few cells disseminated between the collagen fiber bundles at the micro‐scale. The SEM image clearly shows the path of highly cross‐linked collagen fibers, and massive pores exist between the fibers. According to the SEM images, the porosity of the meniscus was 34.1% (34.1% ± 0.032%) and the diameters of the collagen fibers were varied. In addition, the cross‐linking pattern of the fibers was irregular. The scanning accuracy of micro‐MRI was 50 μm. The micro‐MRI demonstrated the outline of the meniscus, but the microstructure was obscure. The micro‐CT clearly displayed microfibers in the meniscus with a voxel size of 11.4 μm. The surface layer, lamellar layer, circumferential fibers, and radial fibers could be identified. The mean porosity of the meniscus according to micro‐CT images was 33.92% (33.92% ± 0.03%). Moreover, a 3D model of the microstructure based on the micro‐CT images was built. The microscale fibers could be displayed in the micro‐CT image and the reconstructed 3D digital model. In addition, a 3D resin model was printed out based on the 3D digital model. Conclusion It is extremely difficult to artificially simulate the microstructure of the meniscus because of the irregularity of the diameter and cross‐linking pattern of fibers. The micro‐MRI images failed to demonstrate the meniscus microstructure. Freeze‐drying and micro‐CT scanning are effective methods for 3D microstructure reconstruction of the meniscus, which is an important step towards mechanically functional 3D‐printed meniscus grafts., Three‐dimensional microstructure reconstruction of the meniscus can be achieved with the method of freeze‐drying and high resolution micro‐CT scanning.

Introduction Previously published articles have suggested that BDNF rs6265 G>A polymorphism is a potential risk factor for epilepsy. However, the results were not consistent. Methods We conducted a meta-analysis to explore the association between BDNF rs6265 G>A polymorphism and epilepsy risk. Four online databases were searched, and related studies were reviewed from their inception up to June 20, 2017. ORs and corresponding 95% CIs were used to calculate the associations of each genetic model. Overall, 10 case-control publications involving 9,512 subjects were included in this meta-analysis. Results Significant associations were found between BDNF rs6265 G>A polymorphism and epilepsy (A vs G: OR=0.88, 95% CI=0.83-0.94, P A polymorphism might be involved in epilepsy susceptibility, especially in the Asian population.

Studies have suggested that phosphatase and tensin homolog (PTEN) plays an important role in neuroprotection and neuronal regeneration. To better understand the potential role of PTEN with respect to peripheral nerve development and injury, we investigated the expression pattern of PTEN at different stages of rat peripheral nerve development and injury and subsequently assessed the effect of pharmacological inhibition of PTEN using bpV(pic) on axonal regeneration in a rat sciatic nerve crush injury model. During the early stages of development, PTEN exhibits low expression in neuronal cell bodies and axons. From embryonic day (E) 18.5 and postnatal day (P)5 to adult, PTEN protein becomes more detectable, with high expression in the dorsal root ganglia (DRG) and axons. PTEN expression is inhibited in peripheral nerves, preceding myelination during neuronal development and remyelination after acute nerve injury. Low PTEN expression after nerve injury promotes Akt/mammalian target of rapamycin (mTOR) signaling pathway activity. In vivo pharmacological inhibition of PTEN using bpV(pic) promoted axonal regrowth, increased the number of myelinated nerve fibers, improved locomotive recovery and enhanced the amplitude response and nerve conduction velocity following stimulation in a rat sciatic nerve crush injury model. Thus, we suggest that PTEN may play potential roles in peripheral nerve development and regeneration and that inhibition of PTEN expression is beneficial for nerve regeneration and functional recovery after peripheral nerve injury.

Acellular nerve allografts can help preserve normal nerve structure and extracellular matrix composition. These allografts have low immunogenicity and are more readily available than autologous nerves for the repair of long-segment peripheral nerve defects. In this study, we repaired a 40-mm ulnar nerve defect in rhesus monkeys with tissue-engineered peripheral nerve, and compared the outcome with that of autograft. The graft was prepared using a chemical extract from adult rhesus monkeys and seeded with allogeneic Schwann cells. Pathomorphology, electromyogram and immunohistochemistry findings revealed the absence of palmar erosion or ulcers, and that the morphology and elasticity of the hypothenar eminence were normal 5 months postoperatively. There were no significant differences in the mean peak compound muscle action potential, the mean nerve conduction velocity, or the number of neurofilaments between the experimental and control groups. However, outcome was significantly better in the experimental group than in the blank group. These findings suggest that chemically extracted allogeneic nerve seeded with autologous Schwann cells can repair 40-mm ulnar nerve defects in the rhesus monkey. The outcomes are similar to those obtained with autologous nerve graft.

The exact inner 3D microstructure of the human peripheral nerve has been a mystery for decades. Therefore, it has been difficult to solve several problems regarding peripheral nerve injury and repair. We used high-resolution X-ray computed microtomography (microCT) to scan a freeze-dried human acellular nerve allograft (hANA). The microCT images were then used to reconstruct a 3D digital model, which was used to print a 3D resin model of the nerve graft. The 3D digital model of the hANA allowed visualization of all planes. The magnified 3D resin model clearly showed the nerve bundles and basement membrane tubes of the hANA. Scanning electron microscopy (SEM) was used to analyse the microstructure of the hANA. Compared to the SEM images, the microCT image clearly demonstrated the microstructure of the hANA cross section at a resolution of up to 1.2 μm. The 3D digital model of the hANA facilitates a clear and easy understanding of peripheral nerve microstructure. Furthermore, the enlarged 3D resin model duplicates the unique inner structure of each individual hANA. This is a crucial step towards achieving 3D printing of a hANA or nerve that can be used as a nerve graft.