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Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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Neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： Carina Hromada Patrick Heimel Markus Kerbl LászlóGál Sylvia Nürnberger Barbara Schaedl James Ferguson Nicole Swiadek Xavier Monforte Johannes C.Heinzel Antal Nógrádi Andreas H.Teuschl-Woller David Hercher department Life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria Ludwig Boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University Clinic of Dentistry Medical University of ViennaViennaAustria department of plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria department of Hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

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Search for microglia-specific peptides:advances in the discovery toolbox

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Neural Regeneration Research 2025年第2期20卷 471-472页

作者： Ivan Sarabia Kyle M.Koss department of surgery University of ArizonaTucsonAZUSA

Uncontrolled and chronic inflammatory states in the central nervous system(CNS)are the hallmark of neurodegenerative pathology and every injury or stroke-related *** key mediators of these neuroinflammatory states are glial cells known as microglia,the resident immune cell at the core of the inflammatory event,and astroglia,which encapsulate inflammatory insults in proteoglycan-rich scar *** gliotic scar blocks significant portions of healthy axonal networking,preventing *** most neuroinflammation is exclusively based on the responses of said microglia,their phenotypes are suggested to follow those of macrophages;M1 and M2 are opposites of pro-and ***,microglial phenotypes have been identified to be on an inflammatory spectrum encompassing developmental,homeostatic,and reparative behaviors as opposed to their ability to affect devastating cell death cascades and scar tissue formation.

关键词： inflammation pathology death

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Regulatory effect and mechanisms of carbon monoxidereleasing molecule Ⅱ on hepatic energy metabolism in septic mice

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World Journal of Gastroenterology 2014年第12期20卷 3301-3311页

作者： Feng Liang Jie Cao Wei-Ting Qin Xu Wang Xue-Feng Qiu Bing-Wei Sun department of burn and plastic surgery Affiliated HospitalJiangsu University

AIM: To investigate the possible mechanisms of exogenous carbon monoxide-releasing molecule II (CORM-2) intervention on hepatic energy metabolism in experimental sepsis.

关键词： Sepsis Carbon monoxide Liver Energy metabolism Regulation

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Promoting axonal regeneration following nerve surgery： a perspective on ultrasound treatment for nerve injuries

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Neural Regeneration Research 2018年第9期13卷 1530-1533页

作者： Konstantin D. Bergmeister Simeon C. Daeschler Patrick Rhodius Philipp Schoenle Arne Bocker Ulrich Kneser Leila Harhaus department of Hand Plastic and Reconstructive Surgery Burn Center Department of Plastic and Hand Surgery University of Heidelberg BG Trauma Hospital Ludwigshafen Ludwigshafen Germany

Nerve injury is often associated with limited axonal regeneration and thus leads to delayed or incomplete axonal *** a consequence of slow nerve regeneration,target muscle function is often insufficient and leads to a lifelong ***,the diagnosis of nerve injuries has been improved and likewise surgical reconstruction has undergone significant ***,the problem of slow nerve regeneration has not been *** a recent meta-analysis,we have shown that the application of low-intensity ultrasound promotes nerve regeneration experimentally and thereby can improve functional *** we want to demonstrate the experimental effect of low intensity ultrasound on nerve regeneration,the current state of investigations and its possible future clinical applications.

关键词： peripheral nerve injuries nerve regeneration reinnervation experimental studies low-intensityultrasound adjunct treatment nerve reconstruction nerve surgery axonal injury

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MicroRNA-451 from Human Umbilical Cord-Derived Mesenchymal Stem Cell Exosomes Inhibits Alveolar Macrophage Autophagy via Tuberous Sclerosis Complex 1/Mammalian Target of Rapamycin Pathway to Attenuate burn-Induced Acute Lung Injury in Rats

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Biomedical and Environmental Sciences 2024年第9期37卷 1030-1043页

作者： Zhigang Jia Lin Li Peng Zhao Guo Fei Shuangru Li Qinqin Song Guangpeng Liu Jisong Liu Affiliated Hospital of Jiang nan University Department of Burn and Plastic SurgeryWuxi 214000JiangsuChina The Third People's Hospital of Bengbu Affiliated to Bengbu Medical University Department of Burn and Plastic SurgeryBengbu 230000AnhuiChina

Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage *** Exosomes were isolated from *** burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 ***-eosin staining evaluated inflammatory ***-linked immunosorbnent assay measured lipopolysaccharide(LPS),tumor necrosis factor-α,and interleukin-1β***-PCR detected miR-451 and tuberous sclerosis complex 1(TSC1)*** regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter *** blotting determined TSC1 and proteins related to the mammalian target of rapamycin(mTOR)pathway and *** analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy *** hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage ***-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted *** miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar *** TSC1 activated mTOR signaling and inhibited autophagy,while TSC1 knockdown reversed the autophagy from the miR-451 *** miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway,providing a potential therapeutic strategy for ALI.

关键词： Acute lung injury Human umbilical cord mesenchymal stem cell-derived exosomes MicroRNA-451 Tuberous sclerosis complex 1 Mammalian target of rapamycin pathway Autophagy

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Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy

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Neural Regeneration Research 2025年第6期20卷 1764-1775页

作者： Zhenzhong Zheng Jialin Chen Jinghong Xu Bin Jiang Lei Li Yawei Li Yuliang Dai Bing Wang department of Spine surgery The Second Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina

Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse *** numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical *** study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic *** analysis identified 128 differentially expressed genes that were enriched in patients with neurological *** least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,*** of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%*** results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

关键词： biomarkers candidate genes degenerative cervical myelopathy gene expression analysis immune cell types neurological disabilities peripheral blood RNA profiles spinal cord injury

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Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders:drug stability,targeting efficiency,and safety

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Neural Regeneration Research 2025年第7期20卷 1883-1899页

作者： Mingyu Zhang Chunyu Xiang Renrui Niu Xiaodong He Wenqi Luo Wanguo Liu Rui Gu department of Orthopedic surgery China-Japan Union Hospital of Jilin UniversityChangchunJilin ProvinceChina

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely ***,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic *** are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and ***,they can potentially treat traumatic and nontraumatic central nervous system *** this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics ***,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain *** studies related to liposomes are still in the laboratory stage and have not yet entered clinical ***,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and ***,we proposed development strategies related to liposomes to further promote their development in neurological disease research.

关键词： Alzheimer's disease amyotrophic lateral sclerosis brain tumors central nervous system Huntington's disease liposome drug delivery neurological disorders Parkinson's disease spinal cord injury traumatic brain injury

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Exosomes originating from neural stem cells undergoing necroptosis participate in cellular communication by inducing TSC2 upregulation of recipient cells following spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3273-3286页

作者： Shiming Li Jianfeng Li Guoliang Chen Tao Lin Penghui Zhang Kuileung Tong Ningning Chen Shaoyu Liu Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research Department of Orthopedic SurgeryThe Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdong ProvinceChina department of Orthopedic surgery The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina department of Orthopedics and Traumatology Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina department of Orthopedic surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina department of Orthopedic surgery The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord *** exosomes are recognized as playing a pivotal role in neural stem cells exocrine function,their precise function in spinal cord injury remains *** investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury,we conducted singlecell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord ***,we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted *** results showed that necroptosis did not significantly impact the fundamental characteristics or number of *** sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs,104 long non-coding RNAs,720 circular RNAs,and 14 microRNAs compared with the control *** of a competing endogenous RNA network identified the following hub genes:tuberous sclerosis 2(Tsc2),solute carrier family 16 member 3(Slc16a3),and forkhead box protein P1(Foxp1).Notably,a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord ***2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury ***,in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other *** assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling *** addition,Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling

关键词： cellular communication competing endogenous RNA exosomes Foxp1 necroptosis neural stem cells Slc16a3 spinal cord injury transcriptome sequencing Tsc2

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Therapeutic effect of autologous concentrated growth factor on lower-extremity chronic refractory wounds:A case report

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World Journal of Clinical Cases 2021年第18期9卷 4797-4802页

作者： Po Liu Yang Liu Chang-Neng Ke Wei-Shan Li Yue-Ming Liu Shi Xu department of burn and plastic surgery Shenzhen Longhua District Central HospitalShenzhen 518110Guangdong ProvinceChina

BACKGROUND Management of chronic refractory wounds is one of the toughest clinical challenges for *** of poor blood supply,less tissue coverage,and easy exposure,the lower leg is a common site for chronic refractory *** current therapeutic regimens often lead to prolonged hospital stay and higher healthcare *** growth factor(CGF)is a novel blood extract that contains various growth factors,platelets,and fibrins to promote wound healing ***,there has been little research reported on the treatment of lower extremity wounds with *** SUMMARY A 37-year-old man,without any past medical history,presented an ulcerated chronic wound on his right lower *** skin defect exhibited clear boundaries,with a size of 2.0 cm×3.5 *** depth of wound was up to the layer of deep *** aureus was detected by bacterial *** final diagnosis was right lower extremity ulcers with ***,silver sulfadiazine,and mupirocin cream were applied to control the *** gel was prepared from the patient’s blood sample,and was used to cover the wound after thorough *** skin wound was successfully healed after three times of CGF *** CGF displays an excellent wound healing promoting effect in patients with lowerextremity chronic refractory wounds.

关键词： Concentrated growth factors Chronic refractory wounds Lower extremity Ulcer Wound healing Case report

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Construction and expression of retroviral vector pLEGFP-N1-TERT in preparation of seed cells for skin tissue engineering

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Asian Pacific Journal of Tropical Medicine 2013年第12期6卷 960-963页

作者： Ting Tan Zhi-Qi Hu Epartment of burn And plastic surgery Fuzhou General Hospital of Nanjing Command.PLA department of plastic surgery Nan fang Hospital of Southern Medical University

Objective:To construct the retroviral vector pLEGFP-N1-telomerase reverse transcriptase(TERT)and to investigate the expression of TERT in neonatal mouse bypodermal ***:The polymerase chain reaction(PCR)-amplified TERT gene was inserted into plasmid *** positive clone was identified by restriction enzyme digestion and sequencing,then was transfected into packaging cells to produce retrovirus *** mouse hypodermal cells were infected with the virus to generate a stable cell *** TERT mRNA expression level,telomerase activity,and enhanced green fluorescent protein(EGFP)expression level were ***:Retroviral vector pLEGFP-N1-TERT was constructed successfully,and a stable cell line of neonatal mouse hypodermal cells expressing EGFP was *** blot and immunohistochemical assay showed that the expression level of TERT was significantly elevated in the neonatal mouse hypodermal ***:A high titer of retrovirus pLEGFP-N1-TERT mediates high-level expression of the exogenous TERT gene in the neonatal mouse hypodermal *** protocol has potential applications for skin tissue engineering and cell transplantation therapy.

关键词： Telomerase reverse transcriptase Retroviral vector Hypodermal cells

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