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, 2019, 3845780
eCollection

Customized Scaffold Design Based on Natural Peripheral Nerve Fascicle Characteristics for Biofabrication in Tissue Regeneration

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Customized Scaffold Design Based on Natural Peripheral Nerve Fascicle Characteristics for Biofabrication in Tissue Regeneration

Zhi Yao et al. Biomed Res Int.

Abstract

Objective: The use of a biofabrication nerve scaffold, which mimics the nerve microstructure, as an alternative for autologous nerve transplantation is a promising strategy for treating peripheral nerve defects. This study aimed to design a customized biofabrication scaffold model with the characteristics of human peripheral nerve fascicles.

Methods: We used Micro-MRI technique to obtain different nerve fascicles. A full-length 28 cm tibial nerve specimen was obtained and was divided into 14 two-centimetre nerve segments. 3D models of the nerve fascicles were obtained by three-dimensional reconstruction after image segmentation. The central line of the nerve fascicles was fitted, and the aggregation of nerve fascicles was analysed quantitatively. The nerve scaffold was designed by simulating the clinical nerve defect and extracting information from the acquired nerve fascicle data; the scaffold design was displayed by 3D printing to verify the accuracy of the model.

Result: The microstructure of the sciatic nerve, tibial nerve, and common peroneal nerve in the nerve fascicles could be obtained by three-dimensional reconstruction. The number of cross fusions of tibial nerve fascicles from proximal end to distal end decreased gradually. By designing the nerve graft in accordance with the microstructure of the nerve fascicles, the 3D printed model demonstrated that the two ends of the nerve defect can be well matched.

Conclusion: The microstructure of the nerve fascicles is complicated and changeable, and the spatial position of each nerve fascicle and the long segment of the nerve fascicle aggregation show great changes at different levels. Under the premise of the stability of the existing imaging techniques, a large number of scanning nerve samples can be used to set up a three-dimensional database of the peripheral nerve fascicle microstructure, integrating the gross imaging information, and provide a template for the design of the downstream nerve graft model.

Conflict of interest statement

All authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
Micro-MRI scanning of the sciatic, tibial, and common peroneal nerves and three-dimensional reconstruction of the nerve fascicles. (a) Sciatic nerve Micro-MRI scan image (A1), two-dimensional image segmentation (A2), and three-dimensional reconstruction of nerve fascicles (A3). (b) Tibial nerve Micro-MRI scan image (B1), two-dimensional image segmentation (B2), and three-dimensional reconstruction of nerve fascicles (B3). (c) Common peroneal nerve Micro-MRI scan image (C1), two-dimensional image segmentation (C2), and three-dimensional reconstruction of nerve fascicles (C3). A2, B2, and C2: scale bar 1 mm; A3, B3, and C3: scale bar 2 mm.
Figure 2
Figure 2
Analysis of morphological cross fusion of long tibial nerve fascicles. A: tibial nerve full-length specimen intercepted. B to O images showed 14 two-centimetre nerve samples taken from proximal end to distal end. In each box from left to right (1–5): Micro-MRI scan images are displayed in each group. In the two-dimensional image, the nerve fascicles were segmented, the nerve fascicles were reconstructed in three dimensions, and the central line was fitted to the three-dimensional reconstruction model. P: the change of the tibial nerve from sciatic nerve branches to the popliteal fossa: cross fusion of the nerve fascicles decreased gradually from proximal to distal. B2 to O2: scale bar 1 mm; B3 to O3, B4 to O4, and B5 to O5: scale bar 2 mm.
Figure 3
Figure 3
Spatial location and distribution change of nerve fascicles in the three-dimensional reconstruction: the distribution of nerve fascicles in the distant, near, and middle segments was intercepted, and the changes of the spatial position of the nerve bundle over a short distance can be observed.
Figure 4
Figure 4
A biofabrication model that mimics the microstructure of peripheral nerve fasciculus was designed based on the three-dimensional database: In scenarios of patients with nerve defects, a nerve graft was designed and customized to the nerve defects. (a) Distal and proximal part of the nerve defect. (b) Differences in the fascicular structure of the distal and proximal part of the nerve defect. (c) The nerve graft was designed according to the three-dimensional database of nerve fasciculus. (d, e, and f) Simulation of the matching between the nerve graft and nerve defect.
Figure 5
Figure 5
The 3D printing model demonstrates the morphological characteristics of the customized nerve graft that mimics the microstructure of the peripheral nerve fasciculus. (a, b) Significant differences in the number and spatial distribution of the nerve fasciculus in the proximal and distal part of the nerve defect. (c) The 3D printing PLA model demonstrates the morphological features of the customized nerve graft, showing the nerve graft and the proximal and distal parts of the nerve defect are well matched. (d, e) The distribution of the two nerve tracts corresponding to the original Micro-MRI scan image. (a, b) Scale bar 1 cm. (c) Scale bar 2 cm. (d, f) Scale bar 1 mm.
Figure 6
Figure 6
The establishment of the database of peripheral nerve microstructure and its application to design a biofabrication nerve graft model according to the morphological characteristics of the nerve bundle. The three-dimensional information database of the peripheral nerve fascicles microstructure was established by scanning peripheral nerve samples using a large number of imaging techniques (Micro-MRI/Micro-CT). When patients with peripheral nerve defects are encountered in the clinic, 3T MRI is used to scan the gross morphology of the nerve trunk of the healthy side and the affected side to locate the damaged area, the size of the defect, and whether the nerve branches were sent out. The model design information was extracted by matching from the database the gross size of the nerve branch and three-dimensional spatial information about the nerve bundle. A biofabrication nerve graft model of the nerve repair material was designed according to the microstructure of the nerve bundle according to the data from clinical MRI nerve trunk scanning.

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