Preclinical assessment on neuronal regeneration in the injury-related microenvironment of graphene-based scaffolds

Qian, Yun; Wang, Xu; Song, Jialin; Chen, Wei; Chen, Shuai; Jin, Y.; Ouyang, Yuanming; Yuan, Weien; Fan, Cunyi

doi:10.1038/s41536-021-00142-2

Cited by 51 publications

(37 citation statements)

References 58 publications

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“…The results indicated that a low concentration of GBN (4% G in the PCL scaffold) might be biocompatible since it exerts no appreciable toxicity in sensitive tissues such as liver, kidney, lung, heart, and spleen in the long-term repair (18 months) of peripheral nerves in vivo. The manufactured scaffold had biologically regenerative effects on myelination, axonal outgrowth, and locomotor function recovery [ 67 ].…”

Section: Tissue-engineered Scaffolds With Gbm and Neural Tissuesmentioning

confidence: 99%

Graphene-Based Materials Prove to Be a Promising Candidate for Nerve Regeneration Following Peripheral Nerve Injury

et al. 2021

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Peripheral nerve injury is a common medical condition that has a great impact on patient quality of life. Currently, surgical management is considered to be a gold standard first-line treatment; however, is often not successful and requires further surgical procedures. Commercially available FDA- and CE- approved decellularized nerve conduits offer considerable benefits to patients suffering from a completely transected nerve but they fail to support neural regeneration in gaps >30 mm. To address this unmet clinical need, current research is focused on biomaterial-based therapies to regenerate dysfunctional neural tissues, specifically damaged peripheral nerve, and spinal cord. Recently, attention has been paid to the capability of graphene-based materials (GBMs) to develop bifunctional scaffolds for promoting nerve regeneration, often via supporting enhanced neural differentiation. The unique features of GBMs have been applied to fabricate an electroactive conductive surface in order to direct stem cells and improve neural proliferation and differentiation. The use of GBMs for nerve tissue engineering (NTE) is considered an emerging technology bringing hope to peripheral nerve injury repair, with some products already in preclinical stages. This review assesses the last six years of research in the field of GBMs application in NTE, focusing on the fabrication and effects of GBMs for neurogenesis in various scaffold forms, including electrospun fibres, films, hydrogels, foams, 3D printing, and bioprinting.

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Section: Tissue-engineered Scaffolds With Gbm and Neural Tissuesmentioning

confidence: 99%

Graphene-Based Materials Prove to Be a Promising Candidate for Nerve Regeneration Following Peripheral Nerve Injury

et al. 2021

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“…Cell adhesion and morphology will be modulated via the signaling pathways. GO of appropriate concentration can also promote cell growth and differentiation [ 60 ]. Some of the cells will gradually grow into the pores, and GO within the porous structure will be in further contact with these cells.…”

Section: Discussionmentioning

confidence: 99%

Graphene oxide-modified silk fibroin/nanohydroxyapatite scaffold loaded with urine-derived stem cells for immunomodulation and bone regeneration

Sun

Xing

et al. 2021

Stem Cell Res Ther

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Background The invasive and complicated procedures involving the use of traditional stem cells limit their application in bone tissue engineering. Cell-free, tissue-engineered bones often have complex scaffold structures and are usually engineered using several growth factors (GFs), thus leading to costly and difficult preparations. Urine-derived stem cells (USCs), a type of autologous stem cell isolated noninvasively and with minimum cost, are expected to solve the typical problems of using traditional stem cells to engineer bones. In this study, a graphene oxide (GO)-modified silk fibroin (SF)/nanohydroxyapatite (nHA) scaffold loaded with USCs was developed for immunomodulation and bone regeneration. Methods The SF/nHA scaffolds were prepared via lyophilization and cross-linked with GO using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxy succinimide (NHS). Scaffolds containing various concentrations of GO were characterized using scanning electron microscopy (SEM), the elastic modulus test, Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectrometer (XPS). Examinations of cell adhesion, proliferation, viability, morphology, alkaline phosphatase activity, and osteogenesis-related gene expression were performed to compare the osteogenesis-related biological behaviors of USCs cultured on the scaffolds. The effect of USC-laden scaffolds on the differentiation of macrophages was tested using ELISA, qRT-PCR, and immunofluorescence staining. Subcutaneous implantations in rats were performed to evaluate the inflammatory response of the USC-laden scaffolds after implantation. The scaffolds loaded with USCs were implanted into a cranial defect model in rats to repair bone defects. Micro-computed tomography (μCT) analyses and histological evaluation were performed to evaluate the bone repair effects. Results GO modification enhanced the mechanical properties of the scaffolds. Scaffolds containing less than 0.5% GO had good biocompatibility and promoted USC proliferation and osteogenesis. The scaffolds loaded with USCs induced the M2-type differentiation and inhibited the M1-type differentiation of macrophages. The USC-laden scaffolds containing 0.1% GO exhibited the best capacity for promoting the M2-type differentiation of macrophages and accelerating bone regeneration and almost bridged the site of the rat cranial defects at 12 weeks after surgery. Conclusions This composite system has the capacity for immunomodulation and the promotion of bone regeneration and shows promising potential for clinical applications of USC-based, tissue-engineered bones.

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“…The sciatic nerve was clearly exposed and excised. Consistent with previous literatures (Qian et al, 2018b(Qian et al, , 2021b, we carried out measurements on the same portion of each nerve and same distance from the point of injury (5 mm distal to the site of crush lesion site). Cross-sections of each sciatic nerve midpoint were cut into 5-µm thick transverse sections on a cryostat.…”

Section: Histological Evaluation Of Regenerated Sciatic Nerve Following Cell Transplantationmentioning

confidence: 97%

Tacrolimus-Induced Neurotrophic Differentiation of Adipose-Derived Stem Cells as Novel Therapeutic Method for Peripheral Nerve Injury

Yao

Yan²,

Li³

et al. 2021

Front. Cell. Neurosci.

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Peripheral nerve injuries (PNIs) are frequent traumatic injuries across the globe. Severe PNIs result in irreversible loss of axons and myelin sheaths and disability of motor and sensory function. Schwann cells can secrete neurotrophic factors and myelinate the injured axons to repair PNIs. However, Schwann cells are hard to harvest and expand in vitro, which limit their clinical use. Adipose-derived stem cells (ADSCs) are easily accessible and have the potential to acquire neurotrophic phenotype under the induction of an established protocol. It has been noticed that Tacrolimus/FK506 promotes peripheral nerve regeneration, despite the mechanism of its pro-neurogenic capacity remains undefined. Herein, we investigated the neurotrophic capacity of ADSCs under the stimulation of tacrolimus. ADSCs were cultured in the induction medium for 18 days to differentiate along the glial lineage and were subjected to FK506 stimulation for the last 3 days. We discovered that FK506 greatly enhanced the neurotrophic phenotype of ADSCs which potentiated the nerve regeneration in a crush injury model. This work explored the novel application of FK506 synergized with ADSCs and thus shed promising light on the treatment of severe PNIs.

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Preclinical assessment on neuronal regeneration in the injury-related microenvironment of graphene-based scaffolds

Cited by 51 publications

References 58 publications

Graphene-Based Materials Prove to Be a Promising Candidate for Nerve Regeneration Following Peripheral Nerve Injury

Graphene-Based Materials Prove to Be a Promising Candidate for Nerve Regeneration Following Peripheral Nerve Injury

Graphene oxide-modified silk fibroin/nanohydroxyapatite scaffold loaded with urine-derived stem cells for immunomodulation and bone regeneration

Tacrolimus-Induced Neurotrophic Differentiation of Adipose-Derived Stem Cells as Novel Therapeutic Method for Peripheral Nerve Injury

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