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Neural Regeneration Research 2025年第7期20卷 2108-2115页

作者： Yuhui Kou Zongxue Jin Yusong Yuan Bo Ma Wenyong Xie Na Han department of trauma and orthopedics Peking University People’s HospitalBeijingChina National Center for trauma Medicine Peking University People’s HospitalBeijingChina Key Laboratory of trauma and Neural Regeneration(Peking University) Ministry of EducationBeijingChina trauma Medicine Center Peking University People’s HospitalBeijingChina department of orthopedics China-Japan Friendship HospitalBeijingChina

FK506(Tacrolimus)is a systemic immunosuppressant approved by the *** and Drug ***506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain *** this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function *** findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.

关键词： FK506 inflammation motor neurons nerve regeneration neuron peripheral nerve injury sensory neurons

Sex-dependent alterations in extracellular vesicles linking chronic spinal cord injury to brain neuroinflammation and neurodegeneration

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Neural Regeneration Research 2025年第2期20卷 483-484页

作者： Yun Li Junfang Wu department of Anesthesiology&Shock Trauma and Anesthesiology Research(STAR)CenterUniversity of Maryland School of MedicineBaltimoreMDUSA

traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability *** in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth *** survival changes have led neurotrauma researchers to examine how SCI interacts with brain *** health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.

关键词： alterations inflammation injury

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

Comparison between direct repair and humana cellular nerve allografting during contralateral C7 transfer to the upper trunk for restoration of shoulder abduction and elbow flexion

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Neural Regeneration Research 2019年第12期14卷 2132-2140页

作者： Liang Li Wen-Ting He Ben-Gang Qin Xiao-Lin Liu Jian-Tao Yang Li-Qiang Gu department of orthopedic trauma and Microsurgery the First Affiliated Hospital of Sun Yat-sen University

Direct coaptation of contralateral C7 to the upper trunk could avoid the interposition of nerve grafts. We have successfully shortened the gap and graft lengths, and even achieved direct coaptation. However, direct repair can only be performed in some selected cases, and partial procedures still require autografts, which are the gold standard for repairing neurologic defects. As symptoms often occur after autografting, human acellular nerve allografts have been used to avoid concomitant symptoms. This study investigated the quality of shoulder abduction and elbow flexion following direct repair and acellular allografting to evaluate issues requiring attention for brachial plexus injury repair. Fifty-one brachial plexus injury patients in the surgical database were eligible for this retrospective study. Patients were divided into two groups according to different surgical methods. Direct repair was performed in 27 patients, while acellular nerve allografts were used to bridge the gap between the contralateral C7 nerve root and upper trunk in 24 patients. The length of the harvested contralateral C7 nerve root was measured intraoperatively. Deltoid and biceps muscle strength, and degrees of shoulder abduction and elbow flexion were examined according to the British Medical Research Council scoring system;meaningful recovery was defined as M3–M5. Lengths of anterior and posterior divisions of the contralateral C7 in the direct repair group were 7.64 ± 0.69 mm and 7.55 ± 0.69 mm, respectively, and in the acellular nerve allografts group were 6.46 ± 0.58 mm and 6.43 ± 0.59 mm, respectively. After a minimum of 4-year follow-up, meaningful recoveries of deltoid and biceps muscles in the direct repair group were 88.89% and 85.19%, respectively, while they were 70.83% and 66.67% in the acellular nerve allografts group. Time to C5/C6 reinnervation was shorter in the direct repair group compared with the acellular nerve allografts group. Direct repair facilitated the restorati

关键词： nerve regeneration contralateral C7 nerve root transfer nerve graft brachial plexus avulsion injury direct repair human acellular nerve allograft shoulder function elbow function nerve transfer phrenic nerve accessary nerve neural regeneration

Contralateral C7 transfer combined with acellular nerve allografts seeded with differentiated adipose stem cells for repairing upper brachial plexus injury in rats

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Neural Regeneration Research 2019年第11期14卷 1932-1940页

作者： Jian-Tao Yang Jin-Tao Fang Liang Li Gang Chen Ben-Gang Qin Li-Qiang Gu department of Microsurgery & orthopedic trauma the First Affiliated Hospital of Sun Yat-sen University

Nerve grafting has always been necessary when the contralateral C7 nerve root is transferred to treat brachial plexus injury. Acellular nerve allograft is a promising alternative for the treatment of nerve defects, and results were improved by grafts laden with differentiated adipose stem cells. However, use of these tissue-engineered nerve grafts has not been reported for the treatment of brachial plexus injury. The aim of the present study was to evaluate the outcome of acellular nerve allografts seeded with differentiated adipose stem cells to improve nerve regeneration in a rat model in which the contralateral C7 nerve was transferred to repair an upper brachial plexus injury. Differentiated adipose stem cells were obtained from Sprague-Dawley rats and transdifferentiated into a Schwann cell-like phenotype. Acellular nerve allografts were prepared from 15-mm bilateral sections of rat sciatic nerves. Rats were randomly divided into three groups: acellular nerve allograft, acellular nerve allograft + differentiated adipose stem cells, and autograft. The upper brachial plexus injury model was established by traction applied away from the intervertebral foramen with micro-hemostat forceps. Acellular nerve allografts with or without seeded cells were used to bridge the gap between the contralateral C7 nerve root and C5–6 nerve. Histological staining, electrophysiology, and neurological function tests were used to evaluate the effect of nerve repair 16 weeks after surgery. Results showed that the onset of discernible functional recovery occurred earlier in the autograft group first, followed by the acellular nerve allograft + differentiated adipose stem cells group, and then the acellular nerve allograft group;moreover, there was a significant difference between autograft and acellular nerve allograft groups. Compared with the acellular nerve allograft group, compound muscle action potential, motor conduction velocity, positivity for neurofilament and S100, diameter o

关键词： nerve regeneration peripheral nerve injury brachial plexus injury contralateral C7 nerve root acellular nerve adipose stem cells Schwann cells tissue engineering nerve nerve grafting nerve defect neural regeneration

Distal femoral extension and shortening osteotomy as a part of multilevel surgery in children with cerebral palsy

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World Journal of Pediatrics 2017年第4期13卷 353-359页

作者： Matthias C.M.Klotz Klemens Hirsch Daniel Heitzmann Michael W.Maier Sebastien Hagmann Thomas Dreher department of orthopedic and trauma Surgery Heidelberg University ClinicsHeidelbergGermany

Background:There are several reports describing an increase in anterior pelvic tilt after hamstring lengthening in children with cerebral palsy (CP).Distal femoral extension and shortening osteotomy (DFESO) is an alternative treatment for correction of flexed knee gait,but investigations analyzing outcome and influence on adjacent joint are few in the *** purpose of this study was to analyze the influence of DFESO on knee and pelvis in children with ***,it was of interest if an additional patellar tendon advancement (PA) influences ***:In this retrospective study,31 limbs of 22 children (GMFCS Ⅰ-Ⅲ;mean age:12.1±3.1 years),who received DFESO were included and kinematic parameters (knee,pelvis) measured by 3-D-gait analysis were compared before and at least 1 year after surgery (mean follow-up period:15.6 months).Results:After surgery,during stance phase minimum knee flexion improved significantly by 20.5° (P<0.001) and mean anterior pelvic tilt increased by 4.0 degrees (P=0.045).In 16 limbs,the postoperative increase in maximum anterior pelvic tilt was more than 5°.Limbs who received an additional PA showed the biggest increase in anterior pelvic ***:DFESO is an effective method for correction of flexed knee gait in children with ***,the results of this study indicate that DFESO may lead to an increase in anterior pelvic tilt,which may lead to a recurrence of flexed knee *** this context,PA seemed to aggravate the effect on the pelvis.

关键词： cerebral palsy femoral extension osteotomy motion analysis

Factors predicting sensory and motor recovery after the repair of upper limb peripheral nerve injuries

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Neural Regeneration Research 2014年第6期9卷 661-672页

作者： Bo He Zhaowei Zhu Qingtang Zhu Xiang Zhou Canbin Zheng Pengliang Li Shuang Zhu Xiaolin Liu Jiakai Zhu department of Microsurgery and orthopedic trauma the First Affiliated Hospital of Sun Yat-sen University

OBJECTIVE： To investigate the factors associated with sensory and motor recovery after the repair of upper limb peripheral nerve injuries. DATA SOURCES： The online PubMed database was searched for English articles describing outcomes after the repair of median, ulnar, radial, and digital nerve injuries in humans with a publication date between 1 January 1990 and 16 February 2011. STUDY SELECTION： The following types of article were selected：（1） clinical trials describ- ing the repair of median, ulnar, radial, and digital nerve injuries published in English; and （2） studies that reported sufficient patient information, including age, mechanism of injury, nerve injured, injury location, defect length, repair time, repair method, and repair materials. SPSS 13.0 software was used to perform univariate and multivariate logistic regression analyses and to in- vestigate the patient and intervention factors associated with outcomes. MAIN OUTCOME MEASURES： Sensory function was assessed using the Mackinnon-Dellon scale and motor function was assessed using the manual muscle test. Satisfactory motor recovery was defined as grade M4 or M5, and satisfactory sensory recovery was defined as grade S3＋ or S4. RESULTS： Seventy-one articles were included in this study. Univariate and multivariate logistic regression analyses showed that repair time, repair materials, and nerve injured were inde- pendent predictors of outcome after the repair of nerve injuries （P 〈 0.05）, and that the nerve injured was the main factor affecting the rate of good to excellent recovery. CONCLUSION： Predictors of outcome after the repair of peripheral nerve injuries include age, gender, repair time, repair materials, nerve injured, defect length, and duration of follow-up.

关键词： nerve regeneration peripheral nerve injury outcome predictors nerve repair upperlimb univariate analysis prognosis 863 Program neural regeneration

Stem cells sources for intervertebral disc regeneration

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World Journal of Stem Cells 2016年第5期8卷 185-201页

作者： Gianluca Vadalà Fabrizio Russo Luca Ambrosio Mattia Loppini Vincenzo Denaro department of orthopedic and trauma Surgery University Campus Bio-Medico of Rome

Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible ***, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers(e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration.

关键词： Stem cells Intervertebral disc degeneration Spine Tissue engineering Cell therapy

The emerging role of tranexamic acid and its principal target,plasminogen,in skeletal health

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2869-2884页

作者： Weixin Xie Antonia Donat Shan Jiang Anke Baranowsky Johannes Keller department of trauma and orthopedic Surgery University Medical Center Hamburg-EppendorfHamburg 20246Germany

The worldwide burden of skeletal diseases such as osteoporosis,degenerative joint disease and impaired fracture healing is steadily *** acid(TXA),a plasminogen inhibitor and anti-fibrinolytic agent,is used to reduce bleeding with high effectiveness and safety in major surgical *** its widespread clinical application,the effects of TXA beyond anti-fibrinolysis have been noticed and prompted renewed interest in its *** clinical trials have characterized the effects of TXA on reducing postoperative infection rates and regulating immune responses in patients undergoing ***,several animal studies suggest potential therapeutic effects of TXA on skeletal diseases such as osteoporosis and fracture *** a direct effect of TXA on the differentiation and function of bone cells in vitro was shown,few mechanisms of action have been ***,we summarize recent findings of the effects of TXA on skeletal diseases and discuss the underlying plasminogen-dependent and-independent mechanisms related to bone metabolism and the immune *** furthermore discuss potential novel indications for TXA application as a treatment strategy for skeletal diseases.

关键词： Tranexamic acid Osteoporosis Osteoarthritis Fracture healing Bone metabolism Inflammation Plasminogen Fibrinolysis

MicroRNA-584-5p/RUNX family transcription factor 2 axis mediates hypoxia-induced osteogenic differentiation of periosteal stem cells

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World Journal of Stem Cells 2023年第10期15卷 979-988页

作者： Jia-Jia Lu Xiao-Jian Shi Qiang Fu Yong-Chuan Li Lei Zhu Nan Lu department of orthopedic trauma Surgery Shanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghai 200001China department of orthopedic trauma Surgery Shanghai Changzheng HospitalShanghai 200001China department of orthopedic trauma Haimen People’s Hospital of Jiangsu ProvinceNantong 226100Jiangsu ProvinceChina

BACKGROUND The hypoxic environment during bone healing is important in regulating the differentiation of periosteal stem cells(PSCs)into osteoblasts or chondrocytes;however,the underlying mechanisms remain *** To determine the effect of hypoxia on PSCs,and the expression of microRNA-584-5p(miR-584-5p)and RUNX family transcription factor 2(RUNX2)in PSCs was modulated to explore the impact of the miR-584-5p/RUNX2 axis on hypoxiainduced osteogenic differentiation of *** In this study,we isolated primary mouse PSCs and stimulated them with hypoxia,and the characteristics and functional genes related to PSC osteogenic differentiation were *** expressing miR-584-5p and RUNX2 were established to determine PSC osteogenic *** Hypoxic stimulation induced PSC osteogenic differentiation and significantly increased calcified nodules,intracellular calcium ion levels,and alkaline phosphatase(ALP)activity in *** differentiation-related factors such as RUNX2,bone morphogenetic protein 2,hypoxia-inducible factor 1-alpha,and ALP were upregulated;in contrast,miR-584-5p was downregulated in these ***,upregulation of miR-584-5p significantly inhibited RUNX2 expression and hypoxia-induced PSC osteogenic ***2 was the target gene of miR-584-5p,antagonizing miR-584-5p inhibition in hypoxia-induced PSC osteogenic *** Our study showed that the interaction of miR-584-5p and RUNX2 could mediate PSC osteogenic differentiation induced by hypoxia.

关键词： Periosteal stem cell Osteogenic differentiation RUNX family transcription factor 2 MiroRNA-584-5p