Novel 3-D helix-flexible nerve guide conduits repair nerve defects

Qi, Qi; Meng, Hui; Chang, Biao; Hong, Lei; Li, Rui; Liu, Guang-Bo; Cheng, Xiaoqing; Tang, He; Liu, Ping; Sun, Yi; Peng, Jiang; Zhao, Qing; Wang, Yu; Lu, Shibi

doi:10.1016/j.biomaterials.2019.03.040

Cited by 43 publications

(50 citation statements)

References 35 publications

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“…Hence, these flexibility and conductivity characteristics of r(GO/GelMA) conduits may provide unconventional performance in potential peripheral nerve regeneration. [ 12,15 ] Mechanical durability of the various conduits was tested by successive compression cycles (Figure 3C). GelMA conduits gradually lost their mechanical strength during compression, displaying ≈37.5% of the initial compressive stress and severe structural damage after 100 cycles of compression.…”

Section: Resultsmentioning

confidence: 99%

“…In practice, NGCs that can withstand dispersive stress and thus maintain their structure are highly desired. [ 15 ] These unique properties appear to be attributed to rGO components, which can strongly interact with gelatin molecules via hydrogen bonding and hydrophobic, van der Waals, and electrostatic interactions. These strong molecular interactions in turn contribute to the elasticity and flexibility of the composite material.…”

Section: Discussionmentioning

confidence: 99%

“…[ 11 ] As NGCs should not collapse and offer a stable mechanical support to growing nerve tissues, NGCs presenting flexibility and kink‐resistance are highly desired. [ 15,16 ] Electrically conductive materials and electrical stimulation through them have been found to promote neurite and axon growth. [ 12,17,18 ] Hence, substantial efforts have been employed to use various electrically conductive materials for the fabrication of NGCs.…”

Section: Introductionmentioning

confidence: 99%

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Electrically Conductive Hydrogel Nerve Guidance Conduits for Peripheral Nerve Regeneration

Park

Jeon

Kim

et al. 2020

Adv Funct Materials

168

111

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Peripheral nerve injuries are serious conditions, and surgical treatment has critical limitations. Therefore, nerve guidance conduits (NGCs) are proposed as an alternative. In this study, multifunctional NGCs are fabricated for the regeneration of injured peripheral nerves. Graphene oxide (GO) and gelatin-methacrylate (GelMA) are polymerized and chemically reduced to form reduced (GO/GelMA) (r(GO/GelMA)). The prepared materials present good electrical conductivity, flexibility, mechanical stability, and permeability, which are suitable for use as NGCs. In vitro studies show 2.1-and 1.4-fold promotion of neuritogenesis of PC12 neuronal cells on r(GO/GelMA) compared to GelMA and unreduced GO/GelMA, respectively. Animal studies using a rat sciatic nerve injury model with a 10 mm gap between the proximal and distal regions of the defect reveal that r(GO/GelMA) NGCs significantly enhance peripheral nerve regeneration, indicated by improved muscle weight increase, electro-conduction velocity, and sciatic nerve function index. Specifically, r(GO/GelMA) NGCs are utilized to potentiate regrowth with myelination in rat sciatic nerves followed by histological, immunohistological, and morphometrical analyses. This study successfully shows the feasibility of electrically conductive hydrogel NGCs as functional conduits for improved nerve regeneration in a preclinical study, where these NGCs can not only mimic nerve tissues but also strongly promote nerve regeneration.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Electrically Conductive Hydrogel Nerve Guidance Conduits for Peripheral Nerve Regeneration

Park

Jeon

Kim

et al. 2020

Adv Funct Materials

168

111

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“…The braided TEX structure encased between the two ES layers is the load-bearing component of the device (Figure 1A). In terms of ultimate tensile strength, SilkBridge TM outperforms not only natural peripheral nerves (Chiono and Tonda-Turo, 2015), but also many other nerve conduit devices made only by electrospun fibers, either based on SF (Dinis et al, 2015) or on other polymers such as PLGA (Hou et al, 2019), PCL (Quan et al, 2019), and PU/gelatin (Salehi et al, 2018). With reference to other nerve conduits with a braided texture made of native SF microfibers (Pillai et al, 2019) or other polymer fibers (PLA/PGA) (Ichihara et al, 2015), the mechanical performance may be similar or better depending on the construction parameter of the textile structure (yarn and fiber size, knit density, etc.).…”

Section: Mechanical Characterizationmentioning

confidence: 99%

Preclinical Validation of SilkBridgeTM for Peripheral Nerve Regeneration

Fregnan

Muratori

Bassani

et al. 2020

Front. Bioeng. Biotechnol.

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Silk fibroin (Bombyx mori) was used to manufacture a nerve conduit (SilkBridge TM) characterized by a novel 3D architecture. The wall of the conduit consists of two electrospun layers (inner and outer) and one textile layer (middle), perfectly integrated at the structural and functional level. The manufacturing technology conferred high compression strength on the device, thus meeting clinical requirements for physiological and pathological compressive stresses. As demonstrated in a previous work, the silk material has proven to be able to provide a valid substrate for cells to grow on, differentiate and start the fundamental cellular regenerative activities in vitro and, in vivo, at the short time point of 2 weeks, to allow the starting of regenerative processes in terms of good integration with the surrounding tissues and colonization of the wall layers and of the lumen with several cell types. In the present study, a 10 mm long gap in the median nerve was repaired with 12 mm SilkBridge TM conduit and evaluated at middle (4 weeks) and at longer time points (12 and 24 weeks). The SilkBridge TM conduit led to a very good functional and morphological recovery of the median nerve, similar to that observed with the reference autograft nerve reconstruction procedure. Taken together, all these results demonstrated that SilkBridge TM has an optimized balance of biomechanical and biological properties, which allowed proceeding with a first-inhuman clinical study aimed at evaluating safety and effectiveness of using the device for the reconstruction of digital nerve defects in humans.

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“…Synthetic NGCs have multiple merits, such as unlimited sources, free of immunogenicity, customizable size and structure, and the potential for incorporating various functions. Therefore, much effort has been dedicated to the development of synthetic NGCs [ [5] , [6] , [7] , [8] , [9] , [10] ]. However, due to the lack of biological factors, satisfying recovery is seldomly achieved with synthetic NGCs alone.…”

Section: Introductionmentioning

confidence: 99%

Polylysine-decorated macroporous microcarriers laden with adipose-derived stem cells promote nerve regeneration in vivo

Sun

Chi

Meng

et al. 2021

Bioactive Materials

Self Cite

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Cell transplantation is an effective strategy to improve the repair effect of nerve guide conduits (NGCs). However, problems such as low loading efficiency and cell anoikis undermine the outcomes. Microcarriers are efficient 3D cell culture scaffolds, which can also prevent cell anoikis by providing substrate for adhesion during transplantation. Here, we demonstrate for the first time microcarrier-based cell transplantation in peripheral nerve repair. We first prepared macroporous chitosan microcarriers (CSMCs) by the emulsion-phase separation method, and then decorated the CSMCs with polylysine (pl-CSMCs) to improve cell affinity. We then loaded the pl-CSMCs with adipose-derived stem cells (ADSCs) and injected them into electrospun polycaprolactone/chitosan NGCs to repair rat sciatic nerve defects. The ADSCs-laden pl-CSMCs effectively improved nerve regeneration as demonstrated by evaluation of histology, motor function recovery, electrophysiology, and gastrocnemius recovery. With efficient cell transplantation, convenient operation, and the multiple merits of ADSCs, the ADSCs-laden pl-CSMCs hold good potential in peripheral nerve repair.

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Novel 3-D helix-flexible nerve guide conduits repair nerve defects

Cited by 43 publications

References 35 publications

Electrically Conductive Hydrogel Nerve Guidance Conduits for Peripheral Nerve Regeneration

Electrically Conductive Hydrogel Nerve Guidance Conduits for Peripheral Nerve Regeneration

Preclinical Validation of SilkBridgeTM for Peripheral Nerve Regeneration

Polylysine-decorated macroporous microcarriers laden with adipose-derived stem cells promote nerve regeneration in vivo

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