XT-type DNA Hydrogels Loaded with VEGF and NGF Promote Peripheral Nerve Regeneration via Biphasic Release Profile

2021 ◽  
Author(s):  
Songyang Liu ◽  
Yijun Liu ◽  
Liping Zhou ◽  
Ci Li ◽  
Meng Zhang ◽  
...  

Peripheral nerve injury (PNI) remains an unresolved challenge in the medicine area. With the development of biomaterial science and tissue engineering, a variety of nerve conduits were widely applied in...

2020 ◽  
Vol 12 (1) ◽  
pp. 56-65 ◽  
Author(s):  
Tianhao Yu ◽  
Yingxi Xu ◽  
Xingya Jia ◽  
Qiang Ao

Peripheral nerve injury that can lead to disability affects millions of people worldwide annually. As the gold standard treatment of peripheral nerve injury, autologous nerve grafts are the most widely used and effective, but the clinical application of the treatment is greatly limited by many disadvantages. Tissue engineering nerve conduits gradually become promising autologous nerve grafts alternatives to promote the regeneration of injured nerves. This review places emphasis on tissue engineering designs of physical and topographic guiding structure inside nerve conduits in order to promote the migration of Schwann cells and directional regrowth of axons towards target organs. Various strategies of intraluminal guiding cues have been described and analyzed, including the incorporation with the tissue with natural basement membrane, collagen, microfilaments, intraluminal multi-channel and grooves in the inner wall. Recently, much progress has been made in the development of tissue engineering nerve conduits, but poor curative effect and deficiencies such as axon dispersion and malposition healing still remain unsolved, many crucial factors need to be considered in further research before clinical practices.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Shimon Rochkind ◽  
Zvi Nevo

Objective. Guiding Regeneration Gel (GRG) was developed in response to the clinical need of improving treatment for peripheral nerve injuries and helping patients regenerate massive regional losses in peripheral nerves. The efficacy of GRG based on tissue engineering technology for the treatment of complete peripheral nerve injury with significant loss defect was investigated.Background. Many severe peripheral nerve injuries can only be treated through surgical reconstructive procedures. Such procedures are challenging, since functional recovery is slow and can be unsatisfactory. One of the most promising solutions already in clinical practice is synthetic nerve conduits connecting the ends of damaged nerve supporting nerve regeneration. However, this solution still does not enable recovery of massive nerve loss defect.The proposed technologyis a biocompatible and biodegradable gel enhancing axonal growth and nerve regeneration. It is composed of a complex of substances comprising transparent, highly viscous gel resembling the extracellular matrix that is almost impermeable to liquids and gasses, flexible, elastic, malleable, and adaptable to various shapes and formats.Preclinical studyon rat model of peripheral nerve injury showed that GRG enhanced nerve regeneration when placed in nerve conduits, enabling recovery of massive nerve loss, previously unbridgeable, and enabled nerve regeneration at least as good as with autologous nerve graft “gold standard” treatment.


2021 ◽  
Vol 9 ◽  
Author(s):  
Shixian Dong ◽  
Sijia Feng ◽  
Yuzhou Chen ◽  
Mo Chen ◽  
Yimeng Yang ◽  
...  

Peripheral nerve injury gives rise to devastating conditions including neural dysfunction, unbearable pain and even paralysis. The therapeutic effect of current treatment for peripheral nerve injury is unsatisfactory, resulting in slow nerve regeneration and incomplete recovery of neural function. In this study, nerve suture combined with ADSCs injection was adopted in rat model of sciatic nerve injury. Under real-time visualization of the injected cells with the guidance of NIR-II fluorescence imaging in vivo, a spatio-temporal map displaying cell migration from the proximal injection site (0 day post-injection) of the nerve to the sutured site (7 days post-injection), and then to the distal section (14 days post-injection) was demonstrated. Furthermore, the results of electromyography and mechanical pain threshold indicated nerve regeneration and functional recovery after the combined therapy. Therefore, in the current study, the observed ADSCs migration in vivo, electrophysiological examination results and pathological changes all provided robust evidence for the efficacy of the applied treatment. Our approach of nerve suture combined with ADSCs injection in treating peripheral nerve injury under real-time NIR-II imaging monitoring in vivo added novel insights into the treatment for peripheral nerve injury, thus further enhancing in-depth understanding of peripheral nerve regeneration and the mechanism behind.


2022 ◽  
Vol 15 ◽  
Author(s):  
Jenica Acheta ◽  
Shannon B. Z. Stephens ◽  
Sophie Belin ◽  
Yannick Poitelon

Peripheral nerve injuries are common conditions that can arise from trauma (e.g., compression, severance) and can lead to neuropathic pain as well as motor and sensory deficits. Although much knowledge exists on the mechanisms of injury and nerve regeneration, treatments that ensure functional recovery following peripheral nerve injury are limited. Schwann cells, the supporting glial cells in peripheral nerves, orchestrate the response to nerve injury, by converting to a “repair” phenotype. However, nerve regeneration is often suboptimal in humans as the repair Schwann cells do not sustain their repair phenotype long enough to support the prolonged regeneration times required for successful nerve regrowth. Thus, numerous strategies are currently focused on promoting and extending the Schwann cells repair phenotype. Low-intensity ultrasound (LIU) is a non-destructive therapeutic approach which has been shown to facilitate peripheral nerve regeneration following nerve injury in rodents. Still, clinical trials in humans are scarce and limited to small population sizes. The benefit of LIU on nerve regeneration could possibly be mediated through the repair Schwann cells. In this review, we discuss the known and possible molecular mechanisms activated in response to LIU in repair Schwann cells to draw support and attention to LIU as a compelling regenerative treatment for peripheral nerve injury.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Hui Liu ◽  
Peizhen Lv ◽  
Yongjia Zhu ◽  
Huayu Wu ◽  
Kun Zhang ◽  
...  

Abstract Salidriside (SDS), a phenylpropanoid glycoside derived from Rhodiola rosea L, has been shown to be neuroprotective in many studies, which may be promising in nerve recovery. In this study, the neuroprotective effects of SDS on engineered nerve constructed by Schwann cells (SCs) and Poly (lactic-co-glycolic acid) (PLGA) were studied in vitro. We further investigated the effect of combinational therapy of SDS and PLGA/SCs based tissue engineering on peripheral nerve regeneration based on the rat model of nerve injury by sciatic transection. The results showed that SDS dramatically enhanced the proliferation and function of SCs. The underlying mechanism may be that SDS affects SCs growth through the modulation of neurotrophic factors (BDNF, GDNF and CNTF). 12 weeks after implantation with a 12 mm gap of sciatic nerve injury, SDS-PLGA/SCs achieved satisfying outcomes of nerve regeneration, as evidenced by morphological and functional improvements upon therapy by SDS, PLGA/SCs or direct suture group assessed by sciatic function index, nerve conduction assay, HE staining and immunohistochemical analysis. Our results demonstrated the significant role of introducing SDS into neural tissue engineering to promote nerve regeneration.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yin Li ◽  
Zhenjiang Ma ◽  
Ya Ren ◽  
Dezhi Lu ◽  
Tao Li ◽  
...  

A peripheral nerve injury (PNI) has severe and profound effects on the life of a patient. The therapeutic approach remains one of the most challenging clinical problems. In recent years, many constructive nerve regeneration schemes are proposed at home and abroad. Nerve tissue engineering plays an important role. It develops an ideal nerve substitute called artificial nerve. Given the complexity of nerve regeneration, this review summarizes the pathophysiology and tissue-engineered repairing strategies of the PNI. Moreover, we discussed the scaffolds and seed cells for neural tissue engineering. Furthermore, we have emphasized the role of 3D printing in tissue engineering.


Author(s):  
Zhiwen Yan ◽  
Cheng Chen ◽  
Gonzalo Rosso ◽  
Yun Qian ◽  
Cunyi Fan

Peripheral nerve tissues possess the ability to regenerate within artificial nerve scaffolds, however, despite the advance of biomaterials that support nerve regeneration, the functional nerve recovery remains unsatisfactory. Importantly, the incorporation of two-dimensional nanomaterials has shown to significantly improve the therapeutic effect of conventional nerve scaffolds. In this review, we examine whether two-dimensional nanomaterials facilitate angiogenesis and thereby promote peripheral nerve regeneration. First, we summarize the major events occurring after peripheral nerve injury. Second, we discuss that the application of two-dimensional nanomaterials for peripheral nerve regeneration strategies by facilitating the formation of new vessels. Then, we analyze the mechanism that the newly-formed capillaries directionally and metabolically support neuronal regeneration. Finally, we prospect that the two-dimensional nanomaterials should be a potential solution to long range peripheral nerve defect. To further enhance the therapeutic effects of two-dimensional nanomaterial, strategies which help remedy the energy deficiency after peripheral nerve injury could be a viable solution.


Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2194
Author(s):  
Yoon-Yen Yow ◽  
Tiong-Keat Goh ◽  
Ke-Ying Nyiew ◽  
Lee-Wei Lim ◽  
Siew-Moi Phang ◽  
...  

Despite the progressive advances, current standards of treatments for peripheral nerve injury do not guarantee complete recovery. Thus, alternative therapeutic interventions should be considered. Complementary and alternative medicines (CAMs) are widely explored for their therapeutic value, but their potential use in peripheral nerve regeneration is underappreciated. The present systematic review, designed according to guidelines of Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols, aims to present and discuss the current literature on the neuroregenerative potential of CAMs, focusing on plants or herbs, mushrooms, decoctions, and their respective natural products. The available literature on CAMs associated with peripheral nerve regeneration published up to 2020 were retrieved from PubMed, Scopus, and Web of Science. According to current literature, the neuroregenerative potential of Achyranthes bidentata, Astragalus membranaceus, Curcuma longa, Panax ginseng, and Hericium erinaceus are the most widely studied. Various CAMs enhanced proliferation and migration of Schwann cells in vitro, primarily through activation of MAPK pathway and FGF-2 signaling, respectively. Animal studies demonstrated the ability of CAMs to promote peripheral nerve regeneration and functional recovery, which are partially associated with modulations of neurotrophic factors, pro-inflammatory cytokines, and anti-apoptotic signaling. This systematic review provides evidence for the potential use of CAMs in the management of peripheral nerve injury.


2012 ◽  
Vol 116 (2) ◽  
pp. 432-444 ◽  
Author(s):  
Meei-Ling Sheu ◽  
Fu-Chou Cheng ◽  
Hong-Lin Su ◽  
Ying-Ju Chen ◽  
Chun-Jung Chen ◽  
...  

Object Increased integration of CD34+ cells in injured nerve significantly promotes nerve regeneration, but this effect can be counteracted by limited migration and short survival of CD34+ cells. SDF-1α and its receptor mediate the recruitment of CD34+ cells involved in the repair mechanism of several neurological diseases. In this study, the authors investigate the potentiation of CD34+ cell recruitment triggered by SDF-1α and the involvement of CD34+ cells in peripheral nerve regeneration. Methods Peripheral nerve injury was induced in 147 Sprague-Dawley rats by crushing the left sciatic nerve with a vessel clamp. The animals were allocated to 3 groups: Group 1, crush injury (controls); Group 2, crush injury and local application of SDF-1α recombinant proteins; and Group 3, crush injury and local application of SDF-1α antibody. Electrophysiological studies and assessment of regeneration markers were conducted at 4 weeks after injury; neurobehavioral studies were conducted at 1, 2, 3, and 4 weeks after injury. The expression of SDF-1α, accumulation of CD34+ cells, immune cells, and angiogenesis factors in injured nerves were evaluated at 1, 3, 7, 10, 14, 21, and 28 days after injury. Results Application of SDF-1α increased the migration of CD34+ cells in vitro, and this effect was dose dependent. Crush injury induced the expression of SDF-1α, with a peak of 10–14 days postinjury, and this increased expression of SDF-1α paralleled the deposition of CD34+ cells, expression of VEGF, and expression of neurofilament. These effects were further enhanced by the administration of SDF-1α recombinant protein and abolished by administration of SDF-1α antibody. Furthermore, these effects were consistent with improvement in measures of neurological function such as sciatic function index, electrophysiological parameters, muscle weight, and myelination of regenerative nerve. Conclusions Expression of SDF-1α facilitates recruitment of CD34+ cells in peripheral nerve injury. The increased deposition of CD34+ cells paralleled significant expression of angiogenesis factors and was consistent with improvement of neurological function. Utilization of SDF-1α for enhancing the recruitment of CD34+ cells involved in peripheral nerve regeneration may be considered as an alternative treatment strategy in peripheral nerve disorders.


2016 ◽  
Vol 80 (1) ◽  
pp. 112-126 ◽  
Author(s):  
J. Michael Hendry ◽  
M. Cecilia Alvarez-Veronesi ◽  
Eva Placheta ◽  
Jennifer J. Zhang ◽  
Tessa Gordon ◽  
...  

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