ACS Nano
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2024
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IF 15.8
Cewen Hu,Bin Liu,Xinyue Huang,Zhilong Wang,Kaiqi Qin,Luyi Sun,Zengjie Fan
Muscle atrophy resulting from peripheral nerve injury (PNI) poses a threat to a patient’s mobility and sensitivity. However, an effective method to inhibit muscle atrophy following PNI remains elusive. Drawing inspiration from the sea cucumber, we have integrated microneedles (MNs) and microchannel technology into nerve guidance conduits (NGCs) to develop bionic microneedle NGCs (MNGCs) that emulate the structure and piezoelectric function of sea cucumbers. Morphologically, MNGCs feature an outer surface with outward-pointing needle tips capable of applying electrical stimulation to denervated muscles. Simultaneously, the interior contains microchannels designed to guide the migration of Schwann cells (SCs). Physiologically, the incorporation of conductive reduced graphene oxide and piezoelectric zinc oxide nanoparticles into the polycaprolactone scaffold enhances conductivity and piezoelectric properties, facilitating SCs’ migration, myelin regeneration, axon growth, and the restoration of neuromuscular function. These combined effects ultimately lead to the inhibition of muscle atrophy and the restoration of nerve function. Consequently, the concept of the synergistic effect of inhibiting muscle atrophy and promoting nerve regeneration has the capacity to transform the traditional approach to PNI repair and find broad applications in PNI repair.
研究领域:
生物医学工程
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神经科学
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材料科学
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DOI
PubMed
高影响因子
MOLECULES
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2022
·Vol. 27
·期 24
·9039
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IF 4.927
Yijie Zhang,Zhiwen Jiang,Yanting Wang,Lixin Xia,Shuqin Yu,Hongjian Li,Wei Zhang,Wanshun Liu,Kai Shao,Baoqin Han
Chitosan (CTS) has been used as a nerve guidance conduit (NGC) material for bridging peripheral nerve defects due to its biocompatible, biodegradable, and non-toxic properties. However, the nerve regeneration effect of chitosan alone is restricted due to its inadequate biological activity. Herein, a composite, bioactive chitosan based nerve conduit, consisting of outer warp-knitted tube scaffold made from medical-grade chitosan fiber, and inner porous cross linked carboxymethyl chitosan (C-CM-CTS) sponge with radial texture was developed. The inner wall of the scaffold was coated with C-CM-CTS solution. CM-CTS provided favorable bioactivities in the composite chitosan-based nerve conduit. An in vitro study of CM-CTS revealed its satisfying biocompatibility with fibroblast and its inhibition of oxidative damage to Schwann cells. As the internal filler of the NGC, the lyophilized sponge of C-CM-CTS showed a longitudinal guidance effect for nerve reconstruction. After 10 mm defect in rat sciatic nerve was bridged with the composite bioactive chitosan-based nerve conduit, the nerve conduit was able to effectively promote axonal regeneration and played a positive role in inducing nerve regeneration and functional recovery. In addition to the functional advantages, which are equal to those of an autograft; the technology for the preparation of this conduit can be put into mass production.Keywords:chitosan;carboxymethyl chitosan;nerve conduit;biocompatibility
研究领域:
生物医学工程
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神经科学
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DOI
PubMed
高影响因子
Journal of Materials Research and Technology-JMR&T
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2021
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IF 5.039
Yuzhe Chen,Wenxuan Zhao,Honglian Dai
Chitosan (CS) is a type of natural polysaccharide, widely used as a biomaterial on account of its great biocompatibility and the multitudes of functional groups on the long chitosan chain, making it easy for property augmentations. Nevertheless, the lack of workability and mechanical capacity limits the applications. Herein, electrospinning was chosen to fabricate oriented chitosan/polyethylene oxide (PEO) nanofibres decorated by integrin-targeting polypeptides (RGD, Arg-Gly-Asp), which is essential for cell adhesion. At the same time, porous PLGA-PEG membranes were taken as a shell of the composite film, which can provide mechanical support for the scaffold. Adequate topological anisotropic information from oriented nanofibres helps the scaffold simulate the natural axon structure, which can induce accelerated regeneration of neurotmesis. Moreover, β-Tricalcium Phosphate (β-TCP) nanoparticles were brought into nanofibers to neutralize the acidic environment produced by the degeneration of PLGA-PEG. Cell viability tests at the in vitro level and dorsal root ganglion (DRG, 1-day sucking SD rat) co-culture detection proved that the scaffold possesses excellent biocompatibility while guiding oriented regeneration of damaged nerves. In this study, a CS-RGD/PEO/β-TCP/PLGA-PEG porous composite scaffold with low cytotoxicity was fabricated. The scaffold can not only lead to the oriented growth of nerves but also has selectivity, which can help nutrient exchange while inhibiting the invasion of fibrous tissue.
研究领域:
生物医学工程
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材料科学
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神经再生
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DOI
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
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2025
·Vol. 113
·期 2
·e37880
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IF 3.9
Yujie Zhu,Chenchen Song,Dongdong Yao,Fangyu Qiao,Yang Zou,Yonggang Lv
The combination of nerve guide conduits (NGCs) and electrical stimulation (ES) is an effective treatment for peripheral nerve injury (PNI). Flexible conductive materials with mechanical properties similar to those of biological tissues have been shown to have better long-term biointegration and functionality than rigid conductive materials. In this study, liquid metal (LM)-based conductive polycaprolactone/gelatin/polypyrrole/LM (PCL/Gel/PPy/LM, PGPL) NGC was combined with exogenous ES to repair PNI. PGPL membranes had good hydrophilicity, degradability, and mechanical properties, and its conductivity reached 0.66 ± 0.02 S/m. In vitro studies showed that the combination of PGPL membranes and ES (2 Hz, 100 mV/cm, 30 min/d) could significantly increase the expression of neuromarkers and had a better pro-neural differentiation effect. In vivo studies demonstrated that PGPL NGCs in combination with ES (2 Hz, 200 mV/mm, 30 min/d) could effectively promote morphological reconstruction and functional recovery of the sciatic nerve in rats. At 3 months post-surgery, PGPL NGCs combined with ES restored the nerve conduction velocity to 73.85% ± 5.45% of the normal value. The LM-based NGCs prepared in this study could effectively repair long sciatic nerve defects, which may further expand the application of LM in the field of nerve tissue engineering.
研究领域:
生物医学工程
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神经科学
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组织工程
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DOI
PubMed
高影响因子
Materials Today Bio
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2024
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IF 8.7
Shuang Liu,Julia Simińska-Stanny,Lizhao Yan,Lihong Fan,Xiaoyue Ding,Tengda Ma,Wei Guo,Yingsong Zhao,Ming Li,Jianghai Chen,Oseweuba Valentine Okoro,Armin Shavandi,Lei Nie
Extensive research efforts are being directed towards identifying alternatives to autografts for the treatment of peripheral nerve injuries (PNIs) with engineered nerve conduits (NGCs) identified as having potential for PNI patients. These NGCs, however, may not fulfill the necessary criteria for a successful transplant, such as sufficient mechanical structural support and functionalization. To address the aforementioned limitations of NGCs, the present investigation explored the development of double cross-linked hydrogels (o-CSMA-E) that integrate the biocompatibility of porcine tendon extracellular matrix (ECM) with the antimicrobial and conductive properties of methacrylated quaternary chitosan. The hydrogels had matrices that could promote the growth of axons and the transmission of neural signals. The hydrogels were subsequently incorporated into a nanofibrous PLLA-ZnO sheath scaffold (ZnO@PLLA) to emulate the natural nerve structure, guiding cell growth and facilitating nerve regeneration. The collaboration of core and sheath materials in ZnO@PLLA/o-CSMA-E nerve guidance conduits resulted in enhanced migration of Schwann cells, formation of myelin sheaths, and improved locomotion performance in rats with sciatic nerve defects when in vivo studies were undertaken. Notably, the in vivo studies demonstrated the similarity between the newly developed engineered NGCs and autologous transplants, with the newly engineered NGCs possessing the potential to promote functional recovery by mimicking the tubular structure and ECM of nerves.
研究领域:
生物医学工程
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神经科学
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组织工程
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DOI
PubMed
高影响因子
Acta Biomaterialia
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2024
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IF 9.4
Yuye Huang,Kai Ye,Andong He,Shaobo Wan,Miaoben Wu,Donghao Hu,Kailei Xu,Peng Wei,Jun Yin
Peripheral nerve injuries (PNIs) can cause neuropathies and significantly affect the patient's quality of life. Autograft transplantation is the gold standard for conventional treatment; however, its application is limited by nerve unavailability, size mismatch, and local tissue adhesion. Tissue engineering, such as nerve guidance conduits, is an alternative and promising strategy to guide nerve regeneration for peripheral nerve repair; however, only a few conduits could reach the high repair efficiency of autografts. The healing process of PNI is frequently accompanied by not only axonal and myelination regeneration but also angiogenesis, which initializes nerve regeneration through vascular endothelial growth factor A (VEGF-A). In this study, a composite nerve conduit with a poly (lactic-co-glycolic acid) (PLGA) hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with VEGF-A transfected Schwann cells (SCs) as the inner layer was established to evaluate its promising ability for peripheral nerve repair. A rat model of peripheral nerve defect was used to examine the efficiency of PLGA/GelMA-SC (VA) conduits, whereas autograft, PLGA, PLGA/GelMA, and PLGA/GelMA-SC (NC) were used as controls. VEGF-A-transfected SCs can provide a stable source for VEGF-A secretion. Furthermore, encapsulation in GelMA cannot only promote proliferation and tube formation of human umbilical vein endothelial cells but also enhance dorsal root ganglia and neuronal cell extension. Previous animal studies have demonstrated that the regenerative effects of PLGA/GelMA-SC (VA) nerve conduit were similar to those of autografts and much better than those of other conduits. These findings indicate that combination of VEGF-A-overexpressing SCs and PLGA/GelMA conduit-guided peripheral nerve repair provides a promising method that enhances angiogenesis and regeneration during nerve repair. Statement of significance Nerve guidance conduits shows promise for peripheral nerve repair, while achieving the repair efficiency of autografts remains a challenge. In this study, a composite nerve conduit with a PLGA hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with vascular endothelial growth factor A (VEGF-A)-transfected Schwann cells (SCs) as the inner layer was established to evaluate its potential ability for peripheral nerve repair. This approach preserves growth factor bioactivity and enhances material properties. GelMA insertion promotes Schwann cell proliferation and morphology extension. Moreover, transfected SCs serve as a stable VEGF-A source and fostering angiogenesis. This study offers a method preserving growth factor efficacy and safeguarding SCs, providing a comprehensive solution for enhanced angiogenesis and nerve regeneration.
研究领域:
组织工程
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神经科学
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生物医学工程
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DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
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2022
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IF 6.064
Li-Ping Nan,Zeng Lin,Feng Wang,Xue-Han Jin,Jia-Qi Fang,Bo Xu,Shu-Hao Liu,Fan Zhang,Zhong Wu,Zi-Fei Zhou,Feng Chen,Wen-Tao Cao,Jian-Guang Wang,Jun-Jian Liu
An electrical signal is the key basis of normal physiological function of the nerve, and the stimulation of the electric signal also plays a very special role in the repair process of nerve injury. Electric stimulation is shown to be effective in promoting axonal regeneration and myelination, thereby promoting nerve injury repair. At present, it is considered that electric conduction recovery is a key aspect of regeneration and repair of long nerve defects. Conductive neural scaffolds have attracted more and more attention due to their similar electrical properties and good biocompatibility with normal nerves. Herein, PCL and MXene-PCL nerve guidance conduits (NGCs) were prepared; their effect on nerve regeneration was evaluated in vitro and in vivo . The results show that the NGCs have good biocompatibility in vitro . Furthermore, a sciatic nerve defect model (15 mm) of SD rats was made, and then the fabricated NGCs were implanted. MXene-PCL NGCs show similar results with the autograft in the sciatic function index, electrophysiological examination, angiogenesis, and morphological nerve regeneration. It is possible that the conductive MXene-PCL NGC could transmit physiological neural electric signals, induce angiogenesis, and stimulate nerve regeneration. This paper presents a novel design of MXene-PCL NGC that could transmit self-originated electric stimulation. In the future, it can be combined with other features to promote nerve regeneration.
研究领域:
神经科学
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生物材料
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组织工程
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生物医学工程
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DOI
PubMed
高影响因子
Bioactive Materials
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2024
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IF 18
Xinqing Wang,Shuo Chen,Xiaolei Chen,Juan Wu,Zhenhua Huang,Jing Wang,Fangping Chen,Changsheng Liu
Peripheral nervous system (PNS) injuries often lead to significant sensory and motor impairments. Traditional artificial nerve conduits, lacking anisotropic structures, have been associated with prolonged repair time and failures in nerve regeneration. This study aimed to address these challenges by developing a novel approach for rapid repair of peripheral nerve injuries (PNI). A 3D oriented fibers scaffold featuring distinct radial (RFs) and longitudinal (LFs) fibers orientations was engineered using coaxial electrospinning and gas directional foaming techniques. This scaffold was then integrated with a shape memory conduit to form a directional multi-channel nerve conduit with micro/nanostructures. The results revealed that the grooved surface of the fibers significantly improved cellular directional guidance, effectively facilitating the migration of SCs from the periphery towards the center and from the base to the apex of the scaffold. In a rat model with a 10 mm nerve defect, the ND-PLATMC/LF ND-PCL scaffold significantly enhanced nerve regeneration and motor function recovery within 4 weeks. These results suggest the potential of this innovative scaffold for efficient repair of the nerve injuries.
研究领域:
生物医学工程
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神经科学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2023
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IF 15.1
Xu Zhang,Tong Qi,Yu Sun,Xinran Chen,Pengxiang Yang,Shuai Wei,Xiyang Cheng,Xiu Dai
Nerve conduits have shown promise as alternatives to autologous nerves, but their repair effects need to be improved. The topographical guidance and functionalization of scaffolds are crucial in nerve repair. In this work, a chitosan-based nerve graft filled with guiding fibres modified by ZIF-8 nanoparticles (CS@ZIF-8) was fabricated for defective nerve repair. An in vitro study demonstrated that CS@ZIF-8 exhibited excellent cytocompatibility and could significantly promote Schwann cell proliferation. In vivo, nerve conduits filled with CS@ZIF-8 were observed to guide stronger axonal longitudinal elongation. Rats bridged with the conduit filled with CS@ZIF-8 showed significant morphological and functional improvements in terms of regenerated nerve density, the number of myelinated nerve fibres, the number of myelin layers, the thickness of myelin sheath, target muscle recovery and sensory function compared to those transplanted with the hollow conduit and the conduit filled with pure chitosan fibres. The repair effects achieved by using the conduit filled with CS@ZIF-8 were similar to those of autografts. Altogether, the data here show that nerve conduits filled with ZIF-8-loaded guide fibres provide a promising approach for repairing nerve defects.
研究领域:
生物医学工程
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神经科学
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组织工程
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产品关联
DOI
高影响因子
BIOMATERIALS
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2025
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IF 12.9
Zhiqiang Li,Junwei Su,Xianzhen Dong,Xinyue Liang,Yuanfang Huo,Junwei Yang,Lesan Yan,Aixi Yu,Honglian Dai
Following peripheral nerve injury (PNI), the early inflammatory response induces excessive production of reactive oxygen species (ROS), resulting in severe damage to the regenerative microenvironment, which poses a huge challenge to the autonomous regeneration of nerves. Exogenous nerve grafts are often needed to assist and guide nerve regeneration. In recent years, nerve conduits (NGCs) with directional structures and favorable bioactivity have made significant progress, but single-function scaffolds still cannot meet the multiple needs of reconstructing an ideal regenerative microenvironment. In this study, a construction strategy for hydrogen-releasing electroactive nerve conduit scaffolds was proposed. The system uses poly(3S-methylmorpholine-2,5-dione-co-ε-caprolactone) [P(MMD-CL)] conduits coated with helically wound metal magnesium wires as a source of gaseous transmitters that continuously release hydrogen. Under the action of an external alternating magnetic field, the magnesium wire coil can form a closed loop and generate weak electrical stimulation (ES). The conduit is further filled with photo-crosslinked lipoic acid-gelatin (Gel-LA) microgels to synergistically regulate cell behavior and assist tissue regeneration. In vitro studies have shown that the system exhibits multiple biological effects, including reducing ROS levels, regulating inflammatory responses, promoting angiogenesis, and maintaining mitochondrial function, reflecting the potential roles of H 2 , ES, and Mg 2+ in regulating the regenerative microenvironment. In vivo , the establishment of a 15 mm sciatic nerve defect model further verified the significant efficacy of the H 2 delivery system in promoting nerve morphology and functional recovery. In summary, this study constructed a multifunctional nerve conduit scaffold with gaseous transmitter delivery, electrical activity regulation, and injectable microgel filling, which provides a new therapeutic idea for improving the post-injury microenvironment and promoting peripheral nerve regeneration, and provides an experimental basis for gas molecule-guided nerve repair strategies.
研究领域:
生物医学工程
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神经生物学
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组织工程
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再生医学
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生物材料学
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神经修复学
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产品关联
DOI
PubMed
高影响因子
Burns & Trauma
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2022
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IF 5.711
Zhang Jing,Tao Jie,Cheng Hao,Liu Haofan,Wu Wenbi,Dong Yinchu,Liu Xuesong,Gou Maling,Yang Siming,Xu Jianguo
BackgroundNerve transfer is an important clinical surgical procedure for nerve repair by the coaptation of a healthy donor nerve to an injured nerve. Usually, nerve transfer is performed in an end-to-end manner, which will lead to functional loss of the donor nerve. In this study, we aimed to evaluate the efficacy of 3D-printed branch nerve conduits in nerve transfer.MethodsCustomized branch conduits were constructed using gelatine-methacryloyl by 3D printing. The nerve conduits were characterized both in vitro and in vivo. The efficacy of 3D-printed branch nerve conduits in nerve transfer was evaluated in rats through electrophysiology testing and histological evaluation.ResultsThe results obtained showed that a single nerve stump could form a complex nerve network in the 3D-printed multibranch conduit. A two-branch conduit was 3D printed for transferring the tibial nerve to the peroneal nerve in rats. In this process, the two branches were connected to the distal tibial nerve and peroneal nerve. It was found that the two nerves were successfully repaired with functional recovery.ConclusionsIt is implied that the two-branch conduit could not only repair the peroneal nerve but also preserve partial function of the donor tibial nerve. This work demonstrated that 3D-printed branch nerve conduits provide a potential method for nerve transfer.
研究领域:
神经科学
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生物医学工程
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组织工程
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2025
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IF 20.3
Anmin Wang,Wenjing Song,Wentai Guo,Baolei Huang,Xingqiang Zhu,Hailin Zhang,Wei Zhai,Ye Tian,Li Ren
Peripheral nerve injuries remain a clinical challenge due to the limitations of autografts and unstable electrical signals in existing bioelectronic therapies. It is necessary to develop innovative strategies to achieve wireless, controllable peripheral neural regeneration (PNR). In this study, we developed a magneto-electric coupling-driven electroactive nerve guidance conduits (PCLG/AgNF NGCs) with a moving magnetic field (MMF) for PNR with wireless magneto-electric coupling electrical stimulation (MECES). PCLG/AgNF displayed high conductivity (25.48 ± 3.77 S/cm) and wireless controllability of generating electrical pulses (16.67 ± 0.47 μA to 475.7 ± 9.71 μA) with an MMF. The MECES produced by PCLG/AgNF with the MMF significantly promoted cell proliferation, cell migration, and upregulated the expression of β3-tubulin, neurofilament heavy chain and growth-associated protein 43, compared to PCLG/AgNF and MMF used individually. Mechanistically, we identified that PCLG/AgNF with the MMF activated the metabolism of taurine and hypotaurine corroborated by elevated intracellular taurine, which is crucial for MECES mediated repair processes. In a rat peripheral nerve defect model, the PCLG/AgNF NGCs with the MMF showed promising results in nerve regrowth, myelination, and functional recovery, performing comparably to autografts. This strategy offers PCLG/AgNF NGCs as a wireless, controllable, precision-enabled approach and provides novel insights for the effective PNR.
研究领域:
生物医学工程
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神经科学
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生物电子学
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组织工程
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再生医学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）