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Biomaterials and tissue engineering in traumatic brain injury:novel perspectives on promoting neural regeneration

neural regeneration Research 2024年第10期19卷 2157-2174页

作者： Shihong Zhu Xiaoyin Liu Xiyue Lu Qiang Liao Huiyang Luo Yuan Tian Xu Cheng Yaxin Jiang Guangdi Liu Jing Chen Department of Neurosurgery West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina National Engineering Research Center for Biomaterials College of Biomedical EngineeringSichuan UniversityChengduSichuan ProvinceChina Department of Anesthesiology West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina Department of Pharmacy West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina Out-patient Department West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina Department of Respiratory and Critical Care Medicine West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina

Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties

关键词： bioactive materials biomaterials exosomes neural regeneration scaffolds stem cells tissue engineering traumatic brain injury

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3D printing of functional bioengineered constructs for neural regeneration: a review

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International Journal of Extreme Manufacturing 2023年第4期5卷 87-118页

作者： Hui Zhu Cong Yao Boyuan Wei Chenyu Xu Xinxin Huang Yan Liu Jiankang He Jianning Zhang Dichen Li State Key Laboratory for Manufacturing Systems Engineering Xi’an Jiaotong UniversityXi’an 710049People’s Republic of China NMPA Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices Xi’an Jiaotong UniversityXi’an 710049People’s Republic of China Department of Neurosurgery The First Medical CenterChinese PLA General HospitalBeijing 100853People’s Republic of China

Three-dimensional(3D)printing technology has opened a new paradigm to controllably and reproducibly fabricate bioengineered neural constructs for potential applications in repairing injured nervous tissues or producing in vitro nervous tissue ***,the complexity of nervous tissues poses great challenges to 3D-printed bioengineered analogues,which should possess diverse architectural/chemical/electrical functionalities to resemble the native growth microenvironments for functional neural *** this work,we provide a state-of-the-art review of the latest development of 3D printing for bioengineered neural *** 3D printing techniques for neural tissue-engineered scaffolds or living cell-laden constructs are summarized and compared in terms of their unique *** highlight the advanced strategies by integrating topographical,biochemical and electroactive cues inside 3D-printed neural constructs to replicate in vivo-like microenvironment for functional neural *** typical applications of 3D-printed bioengineered constructs for in vivo repair of injured nervous tissues,bio-electronics interfacing with native nervous system,neural-on-chips as well as brain-like tissue models are *** challenges and future outlook associated with 3D printing for functional neural constructs in various categories are discussed.

关键词： 3D printing bioengineered neural constructs neural regeneration nerve tissue engineering nervous tissue models

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Glycogen synthase kinase 3 signaling in neural regeneration in vivo

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Journal of Molecular Cell Biology 2023年第12期15卷 1-11页

作者： Jing Zhang Shu-Guang Yang Feng-Quan Zhou Sir Run Run Shaw Hospital Zhejiang University School of MedicineHangzhou 310016China

Glycogen synthase kinase 3(GSK3)signaling plays important and broad roles in regulating neural development in vitro and in ***,we reviewed recent findings of GSK3-regulated axon regeneration in vivo in both the peripheral and central nervous systems and discussed a few controversial findings in the ***,current evidence indicates that GSK3βsignaling serves as an important downstream mediator of the PI3K–AKT pathway to regulate axon regeneration in parallel with the mTORC1 ***,the mTORC1 pathway supports axon regeneration mainly through its role in regulating cap-dependent protein translation,whereas GSK3βsignaling might be involved in regulating N6-methyladenosine mRNA methylation-mediated,cap-independent protein *** addition,GSK3 signaling also plays a key role in reshaping the neuronal transcriptomic landscape during ***,we proposed some research directions to further elucidate the molecular mechanisms underlying the regulatory function of GSK3 signaling and discover novel GSK3 signaling-related therapeutic ***,we hope to provide an updated and insightful overview of how GSK3 signaling regulates neural regeneration in vivo.

关键词： GSK3 neural regeneration protein translation gene transcription

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Low-temperature 3D-printed collagen/chitosan scaffolds loaded with exosomes derived from neural stem cells pretreated with insulin growth factor-1 enhance neural regeneration after traumatic brain injury

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neural regeneration Research 2023年第9期18卷 1990-1998页

作者： Xiao-Yin Liu Yin-He Feng Qing-Bo Feng Jian-Yong Zhang Lin Zhong Peng Liu Shan Wang Yan-Ruo Huang Xu-Yi Chen Liang-Xue Zhou Department of Neurosurgery West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina Tianjin Key Laboratory of Neurotrauma Repair Pingjin Hospital Brain CenterCharacteristic Medical Center of Chinese People’s Armed Police ForceTianjinChina Department of Respiratory and Critical Care Medicine People’s Hospital of Deyang CityAffiliated Hospital of Chengdu College of MedicineDeyangSichuan ProvinceChina Department of Liver Surgery&Liver Transplantation State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengduProvinceChina Department of General Surgery the Affiliated Hospital of Guizhou Medical UniversityGuiyangGuizhou ProvinceChina The First Affiliated Hospital of Chengdu Medical College ChengduSichuan ProvinceChina Department of Anesthesiology Huashan HospitalFudan UniversityShanghaiChina Institute of Medical Security for Maritime Rights Protection of Characteristic Medical Center of Chinese People’s Armed Police Force TianjinChina

There are various clinical treatments for traumatic brain injury,including surgery,drug therapy,and rehabilitation therapy;howeve r,the therapeutic effects are *** combined with exosomes represent a promising but challenging method for improving the repair of traumatic brain *** this study,we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1(3D-CC-INEXOS) to improve traumatic brain injury repair and functional recove ry after traumatic brain injury in *** scaffolds comprising collagen,chitosan,and exosomes derived from neural stem cells pretreated with insulin-like growth fa ctor-1(INEXOS) continuously released exosomes for *** of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model,as assessed by the Morris water maze test and modified neurological seve rity *** addition,immunofluorescence staining and transmission electron microscopy showed that3D-CC-INExos implantation significantly improved the recove ry of damaged nerve tissue in the injured *** conclusion,this study suggests that transplanted3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.

关键词： 3D printing angiogenesis chitosan collagen exosomes functional recovery insulin-like growth factor-1 neural regeneration neural stem cells traumatic brain injury

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Maggot homogenate is associated with neural regeneration and wound healing in the rat

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neural regeneration Research 2010年第8期5卷 623-629页

作者： Zhen Zhang Shouyu Wang Xiliang Tian Zexu Zhao Jianing Zhang Decheng Lv Department of Orthopedic Surgery First Affiliated Hospital of Dalian Medical UniversityDalian 116000Liaoning ProvinceChina Institute of Glycobiology Department of Biochemistry 'Dalian Medical University Dalian 116000 Liaoning Province China

BACKGROUND：Live delivery limits the clinical application of maggot therapy. To date in China, there are no in vivo reports regarding wound healing mechanisms of maggot therapy or the effects of maggot homogenate on wound nerve ***：To avoid complications due to the use of live maggots, an aseptic maggot homogenate was applied. Substance P （SP） and gene protein product 9.5 expression in a cutaneous wound was analyzed to explore possible mechanisms of neural regeneration and wound healing in the ***, TIME AND SETTING：A random grouping and controlled animal study was performed at the laboratory of the Department of Orthopedic Surgery, First Affiliated Hospital, Dalian Medical University from August 2008 to April ***：Live maggots were cultured and provided by the laboratory of the Department of Orthopedic Surgery of the First Affiliated Hospital, Dalian Medical University, ***：A total of 48 adult rats were selected and two acute, full-thickness wounds （round, 1.5 cm diameter） were created on the back of each rat. The two wounds were randomly assigned to homogenate product and control groups. Following two-step disinfection of maggots, a homogenate was produced from 10 maggots and applied to the wound area in the homogenate product group, while the wounds in the control group were treated with normal saline *** OUTCOME MEASURES：On days 1,3, 7, 10, 14, and 21 following injury, the wound tissue was excised. Histological examination of the wound was observed by hematoxylin and eosin staining or Masson＇s Trichrome staining. SP and protein gene product 9.5 expressions were examined by immunohistochemistry to evaluate wound neural ***：On days 7, 10, and 14, the rate of wound healing was significantly greater in the homogenate product group compared with the control group （P 〈 0.05）, and homogenate healing was better than that seen in the control group. On days 3, 7, and 10, SP expression in cells and regener

关键词： maggot therapy wound healing neuropeptides neural regeneration rats maggots maggot homogenate

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Ursolic acid induces neural regeneration after sciatic nerve injury

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neural regeneration Research 2013年第27期8卷 2510-2519页

作者： Biao Liu Yan Liu Guang Yang Zemin Xu Jiajun Chen Department of Hand Surgery China-Japan Union Hospital of Jilin University Department of Neurology China-Japan Union Hospital of Jilin University

In this study, we aimed to explore the role of ursolic acid in the neural regeneration of the injured sciatic nerve. BALB/c mice were used to establish models of sciatic nerve injury through unilateral sciatic nerve complete transection and microscopic anastomosis at 0.5 cm below the ischial tuber-osity. The successful y generated model mice were treated with 10, 5, or 2.5 mg/kg ursolic acid via intraperitoneal injection. Enzyme-linked immunosorbent assay results showed that serum S100 protein expression level gradual y increased at 1-4 weeks after sciatic nerve injury, and significantly decreased at 8 weeks. As such, ursolic acid has the capacity to significantly increase S100 protein expression levels. Real-time quantitative PCR showed that S100 mRNA expression in the L 4-6 segments on the injury side was increased after ursolic acid treatment. In addition, the muscular mass index in the soleus muscle was also increased in mice treated with ursolic acid. Toluidine blue staining revealed that the quantity and average diameter of myelinated nerve fibers in the injured sciatic nerve were significantly increased after treatment with ursolic acid. 10 and 5 mg/kg of ursolic acid produced stronger effects than 2.5 mg/kg of ursolic acid. Our findings indicate that ursolic acid can dose-dependently increase S100 expression and promote neural regeneration in BALB/c mice fol owing sciatic nerve injury.

关键词： neural regeneration traditional Chinese medicine ursolic acid triterpenoid sciatic nerve peripheralnerve injury S100 muscular atrophy nerve myelin sheath grants-supported paper neuroregeneration

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Scientific progress regarding neural regeneration in the Web of Science A 10-year bibliometric analysis

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neural regeneration Research 2013年第36期8卷 3449-3454页

作者： Yuntao Pan Yuhua Zhang Xiaopei Gao Jia Jia Jiping Gao Zheng Ma Institute of Scientific and Technical Information of China (ISTIC)

BACKGROUND： neural regeneration following nerve injury is an emerging field that attracts ex- tending interests all over the world. OBJECTIVE： To use bibliometric indexes to track studies focusing on neural regeneration, and to investigate the relationships among geographic origin, countries and institutes, keywords in the published articles, and especially focus on the region distribution, institution distribution, as well as collaborations in Chinese papers indexed in the Web of Science. METHODS： A list of neural regeneration studies was generated by searching the database of the Web of Science-Expanded using the term ＂neural Regenera＊＂. Inclusive criteria：（1） articles in the field of neural regeneration; （2） fundamental research on animals, clinical trials and case reports; （3） article types： article, review, proceedings paper, note, letter, editorial material, discussion, book chapter; （4） year of publication： 2003-2012; and （5） citation database： Science Citation Index-Expanded. Exclusive criteria：（1） articles requiring manual searching or with access only by telephone; （2） unpublished articles; and （3） corrections. RESULTS： A total of 4 893 papers were retrieved from the Web of Science published between 2003 and 2012. The papers covered 65 countries or regions, of which the United States ranked first with 1 691 papers. The most relevant papers were in the neurosciences and cell biology, and the key- word ＂stem cell＂ was the most frequent. In recent years, China showed a great increase in the number of papers. Over the entire 10 years, there were 922 Chinese papers, with Jilin University ranking first with 58 articles. Chinese papers were published in connection with many countries, in- cluding the United States, Japan, and the United Kingdom. Among the connections, the papers published by the Chinese and the American are 107, with the highest rate. With regard to funding, 689 articles were funded from various projects, occupying 74.72% of the total amount. I

关键词： neural regeneration bibliometrics neurogenesis neuroplasticity neuroprotective neuromodulatory neurorestoration stem cells neurodegenerative disease grants-supported paper neuroregeneration

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Rhesus monkey neural stem cell transplantation promotes neural regeneration in rats with hippocampal lesions

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neural regeneration Research 2016年第9期11卷 1464-1470页

作者： Li-juan Ye Hui Bian Yao-dong Fan Zheng-bo Wang Hua-lin Yu Yuan-ye Ma Feng Chen Department of Pathology Third Affiliated Hospital of Kunming Medical University Kunming Yunnan Province China Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan Province China Department of Physiology Kunming Medical University Kunming Yunnan Province China Second Department of Neurosurgery First Affiliated Hospital of Kunming Medical University Kunming Yunnan Province China Department of Radiology Hainan General Hospital Haikou Hainan Province China

Rhesus monkey neural stem cells are capable of differentiating into neurons and glial cells. Therefore, neural stem cell transplantation can be used to promote functional recovery of the nervous system. Rhesus monkey neural stem cells （1 ×10^5 cells/μL） were injected into bilateral hippocampi of rats with hippocampal lesions. Confocal laser scanning microscopy demonstrated that green fluorescent protein-la- beled transplanted cells survived and grew well. Transplanted cells were detected at the lesion site, but also in the nerve fiber-rich region of the cerebral cortex and corpus callosum. Some transplanted cells differentiated into neurons and glial cells clustering along the ventricular wall, and integrated into the recipient brain. Behavioral tests revealed that spatial learning and memory ability improved, indicating that rhesus monkey neural stem cells noticeably improve spatial learning and memory abilities in rats with hippocampal lesions.

关键词： nerve regeneration rhesus monkey neural stem cells hippocampal lesion cell transplantation spatial learning and memory abilities neural regeneration

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Translocator protein ligand, YL-IPA08, attenuates lipopolysaccharide-induced depression-like behavior by promoting neural regeneration

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neural regeneration Research 2018年第11期13卷 1937-1944页

作者： Xiao-Ying Zhang Li-Ming Zhang Wei-Dong Mi Yun-Feng Li Anesthesia and Operation Center Chinese PLA General Hospital Beijing China State Key Laboratory of Toxicology and Medical Countermeasures Beijing China

Translocator protein has received attention for its involvement in the pathogenesis of depression. This study assessed the effects of the new translocator protein ligand, YL-IPA08, on alleviating inflammation-induced depression-like behavior in mice and investigated its mechanism of action. Mice were intracerebroventricularly injected with 1, 10, 100 or 1000 ng lipopolysaccharide. The tail-suspension test and the forced swimming test confirmed that 100 ng lipopolysaccharide induced depression-like behavior. A mouse model was then established by intraventricular injection of 100 ng lipopolysaccharide. On days 16-24 after model establishment, mice were intragastrically administered 3 mg/kg YL-IPA08 daily. Immunohistochemistry was used to determine BrdU and NeuN expression in the hippocampus. YL-IPA08 effectively reversed the depression-like behavior of lipopolysaccharide-treated mice, restored body mass, increased the number of BrdU-positive cells, and the number and proportion of BrdU and NeuN double-positive cells. These findings indicate that YL-IPA08 can attenuate lipopolysaccharide-induced depression-like behavior in mice by promoting the formation of hippocampal neurons.

关键词： nerve regeneration YL-IPA08 hippocampus dentate gyrus lipopolysaccharide neuroinflammation depression translocator protein neural regeneration

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Effect of electrical stimulation on neural regeneration via the p38-RhoA and ERK1/2-Bcl-2 pathways in spinal cord-injured rats

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neural regeneration Research 2018年第2期13卷 340-346页

作者： Min Cheol Joo Chul Hwan Jang Jong Tae Park Seung Won Choi Seungil Ro Min Seob Kim Moon Young Lee Department of Rehabilitation Medicine and Institute of Wonkwang Medical Science School of Medicine Wonkwang University Department of Neurosurgery School of Medicine Wonkwang University Department of Anesthesiology and Pain Medicine School of Medicine Wonkwang University Department of Physiology and Cell Biology School of Medicine University of Nevada Department of Physiology and Institute of Wonkwang Medical Science School of Medicine Wonkwang University

Although electrical stimulation is therapeutically applied for neural regeneration in patients, it remains unclear how electrical stimulation exerts its effects at the molecular level on spinal cord injury （SCI）. To identify the signaling pathway involved in electrical stimulation improving the function of injured spinal cord, 21 female Sprague-Dawley rats were randomly assigned to three groups： control （no surgical intervention, n = 6）, SCI （SCI only, n = 5）, and electrical simulation （ES; SCI induction followed by ES treatment, n = 10）. A complete spinal cord transection was performed at the 10^th thoracic level. Electrical stimulation of the injured spinal cord region was applied for 4 hours per day for 7 days. On days 2 and 7 post SCI, the Touch-Test Sensory Evaluators and the Basso-Beattie-Bresnahan locomotor scale were used to evaluate rat sensory and motor function. Somatosensory-evoked potentials of the tibial nerve of a hind paw of the rat were measured to evaluate the electrophysiological function of injured spinal cord. Western blot analysis was performed to measure p38-RhoA and ERK1/2-Bcl-2 pathways related protein levels in the injured spinal cord. Rat sensory and motor functions were similar between SCI and ES groups. Com- pared with the SCI group, in the ES group, the latencies of the somatosensory-evoked potential of the tibial nerve of rats were significantly shortened, the amplitudes were significantly increased, RhoA protein level was significantly decreased, protein gene product 9.5 expression, ERK1/2, p38, and Bcl-2 protein levels in the spinal cord were significantly increased. These data suggest that ES can promote the recovery of electrophysiological function of the injured spinal cord through regulating p38-RhoA and ERK1/2-Bcl-2 pathway-related protein levels in the injured spinal cord.

关键词： Bcl-2 ERKI/2 p38 PGP9.5 RhoA spinal cord injury somatosensory evoked potential muscle contraction electrical impulses neural regeneration

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