Design and optimization of a biodegradable porous zein conduit using microtubes as a guide for rat sciatic nerve defect repair

Wang, Guowu; Yang, Hui; Wang, Weifeng; Zhang, Ping; Wang, Jin‐Ye

doi:10.1016/j.biomaterials.2017.03.038

Cited by 59 publications

(53 citation statements)

References 48 publications

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“…The rats showed improved gait 2 months after implantation. The porous zein conduit showed significantly increased density of myelinated nerve fibers and increased myelin sheath thickness at 2-and 4-months post-implantation (Wang et al, 2017). The porous nature of these zein NGCs enabled nutrient diffusion and facilitated eventual degradation of the scaffold over the course of 4 months, when nerve regeneration in the conduit with microtubes was comparable to the regeneration observed in autograft controls (Wang et al, 2017).…”

Section: Topographical Cues Drive Alignment and Directionalitymentioning

confidence: 93%

Biomaterials for Enhancing Neuronal Repair

Cangellaris

Gillette

2018

Front. Mater.

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As they differentiate from neuroblasts, nascent neurons become highly polarized and elongate. Neurons extend and elaborate fine and fragile cellular extensions that form circuits enabling long-distance communication and signal integration within the body. While other organ systems are developing, projections of differentiating neurons find paths to distant targets. Subsequent post-developmental neuronal damage is catastrophic because the cues for reinnervation are no longer active. Advances in biomaterials are enabling fabrication of micro-environments that encourage neuronal regrowth and restoration of function by recreating these developmental cues. This mini-review considers new materials that employ topographical, chemical, electrical, and/or mechanical cues for use in neuronal repair. Manipulating and integrating these elements in different combinations will generate new technologies to enhance neural repair.

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Section: Topographical Cues Drive Alignment and Directionalitymentioning

confidence: 93%

Biomaterials for Enhancing Neuronal Repair

Cangellaris

Gillette

2018

Front. Mater.

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“…The grounding pin was plugged to the tail (Wang, Yang, Wu, Zhang, & Wang, 2017;Wu et al, 2016). All animals were analyzed with the use of an electromyograph (Nicolet, United States).…”

Section: Electrophysiological Evaluationmentioning

confidence: 99%

3D‐engineered GelMA conduit filled with ECM promotes regeneration of peripheral nerve

Gong

Fei

et al. 2019

J Biomedical Materials Res

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Autologous transplantation remains the golden standard for peripheral nerve repair.However, many drawbacks, such as the risk of reoperation or nerve injury remain associated with this method. To date, commercially available artificial nerve conduits comprise hollow tubes. By providing physical guiding and biological cues, tissue engineered conduits are promising for bridging peripheral nerve defects. The present study focuses on the preparation of artificial composite nerve conduits by 3D bio-printing. 3D-printed molds with a tubular cavity were filled with an Engelbreth-Holm-Swarm (EHS) Hydrogel mimicking the extracellular matrix (ECM) basement membrane. Chemically cross-linked gelatin methacryloyl (GelMA) was used to form the conduit backbone, while EHS Hydrogels improved nerve fiber growth while shortening repair time. Statistical significant difference had been found between the blank conduit and the composite conduit group on compound muscle action potential after 4 months. On the other hand, results between the composite conduit group and the autograft group were of no statistical differences.All results above showed that the composite conduit filled with EHS Hydrogel can promote the repair of peripheral nerve and may become a promising way to treat peripheral nerve defects.3D bioprint, chemical cross-link, ECM, GelMA, nerve repair Conduits were produced as described earlier (Hu et al., 2016). Briefly, the mold (Figure 1a,b) was modeled with the use of SolidWorks to create a tubular cavity prior to 3D printing. Based on the size of rat sciatic nerves, the inner and outer diameters were 2 and 4 mm, respectively (Zhao et al., 2016). Five percentage of GelMA (SE-3DP-0200, StemEasy Biotech, China) aqueous solution was prepared at 60 C. After complete dissolution, the solution was cooled to 15 C prior to the addition of 0.5% APS and 0.1% TEMED. The mixture was then poured into the mold and rapidly placed at −20 C. After 24 hr of solidification, the conduit was defrosted and unmolded, followed by intensive rinsing and freeze-drying.For EHS Hydrogel (SE-EHS-0100, StemEasy Biotech, China) filling, conduits were placed on precooled petri-dishes and 0.1 ml of EHS Hydrogel was poured into the cavity. Conduits were then immediately placed in an incubator. After 5 min, the EHS Hydrogel displayed a jellylike texture and the composite conduit was considered ready to use.According to the conventional method, the blank GelMA conduit was examined by scanning electron microscopy (SEM, Phenom ProX, Thermo fisher), and the images were analyzed by ImageJ to calculate the porosity. The blank conduits were immersed in saline in 37 C, and the swelling ratio was calculated by weighing before and after at different time points and calculated by the following formula (Zhao et al., 2016):Swelling ratio = wet weight− dry weight dry weight × 100%The mechanical properties of GelMA blank conduits were also evaluated by both compression and tensile tests using universal testing systems (5969, Instron, United States) equipped with a 50 N loa...

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“…The conduits with three‐dimensional structures can mimic the structure of natural extracellular matrix components and provide appropriate condition for nerve regeneration, which have great potential applications in repairing peripheral nerve injury . The zein conduit including intraluminal microtubes has been demonstrated to be able to promote the regeneration and functional recovery of injury nerve successfully, which achieved a comparable repairing efficacy to autograft . The better repairing effect of conduits may be obtained further by designing a three‐dimensional conductive conduit.…”

Section: Disscusionmentioning

confidence: 99%

“…In contrast, the optimal recovery in muscle weight was still presented in autograft. The inconsistent result between electrophysiology and muscle weight recovery in conduit groups may be ascribed to the faster degradation of microtubes, which leads to the incorrect reinnervation of nerve to muscle and slow growth of atrophic muscle …”

Section: Disscusionmentioning

confidence: 99%

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Intact polyaniline coating as a conductive guidance is beneficial to repairing sciatic nerve injury

Wang

Yang

et al. 2019

J Biomed Mater Res

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Endowing the conduit with conductivity has been an effective way to stimulate nerve growth and functional recovery. Here, conducting polyaniline (PANi) was used to construct a conductive guidance by coating on the surface of microtubes inserted in a three‐dimensional zein nerve conduit to study the repairing efficacy on peripheral nerve injury. PANi nanoparticles with a size of 20–30 nm were synthesized and coated on the surface of microtubes through layer‐by‐layer deposition. Then, conduits including microtubes with and without PANi coating were implanted into rats to bridge a 10‐mm sciatic nerve defect and autograft as the control group. After 2 months, the conduit with PANicoating improved the recovery of proximal compound muscle action potential significantly in the regenerated nerve compared to the conduit without PANi coating, which was not inferior to the autograft group. However, the repairing efficacy was changed reversely at the fourth month postimplantation. PANi coating fragmented to form debris within or around the regenerated nerves while microtubes seem to degrade completely as observed by H&E staining. In vitro degradation experiment confirmed this process. The PANi nanoparticles could induce cytotoxicity and reactive oxygen species (ROS) generation of both NIH 3T3 cells and macrophage cell line RAW 264.7. These in vitro and in vivo results implied that the nondegradable PANi may occupy the regeneration space and stimulate the inflammatory response in later implantation in vivo. While there was no such risk if the PANi coating keeps in an intact film. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:128–142, 2020.

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Design and optimization of a biodegradable porous zein conduit using microtubes as a guide for rat sciatic nerve defect repair

Cited by 59 publications

References 48 publications

Biomaterials for Enhancing Neuronal Repair

Biomaterials for Enhancing Neuronal Repair

3D‐engineered GelMA conduit filled with ECM promotes regeneration of peripheral nerve

Intact polyaniline coating as a conductive guidance is beneficial to repairing sciatic nerve injury

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