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BACKGROUND:Bone wax is a filler that can be used for bone hemostasis.Although modification of bone wax formulations is attempted worldwide,its inertness is still the main challenge today.There is an urgent clinical need to develop novel orthopedic hemostatic materials with hemostasis,osteogenesis and antibacterial properties. OBJECTIVE:To review the development of orthopedic hemostatic materials including bone wax and its substitutes. METHODS:PubMed,Web of Science,WanFang,CNKI and VIP databases were searched for literature related to bone wax,hemostatic materials,and research progress of orthopedic hemostatic materials,and 136 articles were selected for inclusion in the review by reading the abstracts of the articles in the initial screening. RESULTS AND CONCLUSION:To replace traditional bone wax,researchers have developed various orthopedic hemostatic materials based on the needs of practical scenarios such as hemostasis and osteogenesis.However,relevant studies mostly focus on basic physical and chemical and performance tests,lack a systematic evaluation system,and lack sufficient reports of large animal experiments and clinical trials.Therefore,bone wax is still a recognized orthopedic hemostatic material at present.The fundamental reason is that the design of existing materials cannot timely meet the new needs of intraoperative hemostasis,postoperative osteogenesis and clinical practice.In the future,the structure,composition and function of existing hemostatic and osteogenic materials need to be integrated and redesigned to meet the increasing demand for hemostatic and osteogenic materials.
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Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.
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Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.
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Most patients with spinal cord injury suffer from limb motor dysfunction. Given drugs, surgery and other conventional treatments are often not effective, the patients can only rely on a wheelchair to move or even lie in bed for a long time, seriously affecting their quality of life. Brain computer interface (BCI) technology provides a non-muscular pathway for the recovery of motor function in patients with spinal cord injury, which allows the patients to recover partial motor function through the normal function of their own non-diseased spinal cord or external mechanical devices. After decades of development of BCI technology, signal collection devices can identify and collect the motor signals of the brain more accurately, transform the signal by characteristic analysis, and implement the brain command by using the output device. A large number of experimental and clinical studies have also proved that the application of BCI technology in patients with spinal cord injury can partially improve the motor function of upper and lower limbs. Therefore, BCI technology has attracted more and more attention. The authors summarized the BCI technology and its influence on motor function rehabilitation in patients with spinal cord injury, so as to provide a reference for the rehabilitation of motor function in patients with spinal cord injury.
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Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.
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Objective:To evaluate the clinical outcomes of internal fixation using double reverse traction reducers in the treatment of tibial plateau fractures.Methods:This study retrospectively examined the medical records of 48 patients who underwent surgical intervention for tibial plateau fractures at the Affiliated Hospital of Qingdao University between January 2021 and September 2022. The cohort, aged between 35 to 68 years (mean: 53.0±7.9 years), included 23 males and 25 females. Fractures were classified according to the Schatzker system, with 9 type III, 23 type IV, 11 type V, and 5 type VI fractures recorded. Patients were divided into two groups based on the surgical approach: the minimally invasive group underwent treatment with double reverse traction reducers for reduction and internal fixation in 24 cases, while the open group received conventional open reduction and internal fixation in 24 cases. Comparative parameters included operation duration, intraoperative blood loss, hospital stay, early postoperative knee mobility, and weight-bearing timelines. Postoperative radiographic images were appraised using the Rasmussen imaging score, and knee functionality was assessed at the final follow-up with the Hospital for Special Surgery (HSS) score and the International Knee Documentation Committee (IKDC) score.Results:The preoperative general data were statistically indifferent between groups ( P>0.05). All patients were followed for 13.5±4.3 months (range, 9.5-24 months). In the minimally invasive group, operative time was 88.96±19.04 minutes, intraoperative blood loss was 65±32 ml, and hospital stay was 11.8±3.9 days. Early postoperative knee joint activity commenced at 8.96±2.84 days, significantly earlier compared to the open group, which recorded 178.63±67.75 minutes of surgery, 114.16±65.05 ml blood loss, a 15.3±4.8 days hospital stay, and 16.83±4.09 days to knee joint movement. The difference was statistically significant ( P<0.05). No significant variation was observed in the time to bone healing between the minimally invasive group at 12.6±3.8 weeks and the open group at 13.21±4.98 weeks ( P>0.05). Rasmussen imaging criteria revealed 21 excellent and 3 good outcomes in the minimally invasive group, and 19 excellent and 5 good in the open group, with no statistical significance in the excellent-good rate differentiation ( P>0.05). Bone healing occurred within 3.2±0.8 months (range, 2.5-6.0 months), with 79% (19/24) in the minimally invasive group and 75% (18/24) in the open group achieving healing within 3 months. The open group had one incidence of superficial skin infection, and one patient in the minimally invasive group developed deep vein thrombosis (DVT); no other related complications were documented. Conclusion:Minimally invasive treatment of tibial plateau fractures using double reverse traction reducers offers significant benefits, including reduced surgical time, minimal blood loss, less soft tissue trauma, and enhanced joint function recovery. This approach is particularly advantageous in managing complex tibial plateau fractures compared to traditional open reduction and internal fixation methods.
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Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.
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Objective:To compare the clinical efficacy between modified open wedge high tibial osteotomy (MOWHTO) versus traditional open wedge high tibial osteotomy (TOWHTO) for varus knee osteoarthritis (KOA).Methods:A retrospective study was conducted to analyze the 50 patients (60 knees) with varus KOA who had received high tibial osteotomy at Department of Sports Medicine, The Affiliated Hospital of Qingdao University between September 2019 and December 2020. The patients were divided into 2 groups according to different ways of osteotomy: a traditional group and a modified group. In the traditional group subjected to TOWHTO, there were 25 cases (30 knees); in the modified group subjected to MOWHTO, there were 25 cases (30 knees). In MOWHTO, the bone block attached to the medial collateral ligament (MCL) of the knee was first chiseled at the MCL insertion before osteotomy to reduce excessive stripping of the MCL in the osteotomy area, and then the bone fragment attached to the MCL was filled into the osteotomy area to increase bone filling and bone coverage after the alignment of the lower limb was corrected. The hip-knee-ankle angle (HKAA), medioproximal tibial angle (MPTA), and joint line convergence angle (JLCA) were measured preoperatively and at 18 months postoperatively in both groups to evaluate correction of the alignment of the lower limb. Fracture healing time, bone loss in the osteotomy area, Hospital for Special Surgery (HSS) knee score and visual analogue scale (VAS) were recorded to evaluate the postoperative efficacy.Results:There was no statistically significant difference between the TOWHTO and MOWHTO groups in the general clinical data before operation, showing comparability ( P>0.05). At 18 months after operation, HKAA was (179.1° ± 1.1°) in the TOWHTO group and (179.3° ± 0.7°) in the MOWHTO group while MPTA was (91.9° ± 0.4°) in the TOWHTO group and (91.9° ± 0.4°) in the MOWHTO group, showing no statistically significant difference between the 2 groups ( P>0.05) but a significant difference between preoperation and postoperation in each group ( P<0.05). At 18 months after operation, JLCA was (1.8° ± 0.4°) in the TOWHTO group, significantly larger than that in the MOWHTO group (1.5° ± 0.4°), HSS score was 81.5 (79.5, 83.0) points in the TOWHTO group, significantly lower than that in the MOWHTO group [85.0 (82.5, 87.5) points], and VAS was 1.8 (1.6, 2.0) points in the TOWHTO group, significantly higher than that in the MOWHTO group [1.5 (1.5, 2.0) points] (all P<0.05). At 18 months after operation, the preoperative JLCA was significantly improved in both groups ( P<0.05). The time required for a fracture healing score higher than 4 points was (3.3 ± 0.6) months in the TOWHTO group and (4.5 ± 0.9) months in the MOWHTO group, and the rate of bone loss in the osteotomy area was 20% in the TOWHTO group (6/30) and 0 (0/30) in the MOWHTO group, both showing a significant difference between the 2 groups ( P<0.05). Conclusions:Both TOWHTO and MOWHTO can effectively treat varus KOA. MOWHTO is more effective in promoting bone healing in the osteotomy area, reducing bone defects in the osteotomy area and improving knee function.
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Objective:To analyze the risk factors for rotator cuff tear and evaluate the corresponding prediction efficacy.Methods:A case-control study was conducted in 69 patients with rotator cuff tear admitted to Affiliated Hospital of Qingdao University from June 2020 to June 2021 (rotator cuff tear group) and 51 normal volunteers or medical examiners (normal control group). There were 55 males and 65 females, with the age range of 34-77 years [(58.2±7.2)years]. Body mass index (BMI) ranged from 19.5-32.4 kg/m 2 [(25.4±2.5)kg/m 2]. Univariate analysis was performed for the correlation of gender, age, history of hypertension, history of smoking, history of diabetes, BMI, angle of humeral greater tuberosity and notch angle of humeral greater tuberosity with rotator cuff tear in the two groups. Factors with statistically significant differences were included in multivariate Logistic regression analysis to determine the independent risk factors for rotator cuff tear. Spearman correlation analysis was used to find factor correlation between the two groups. The receiver operating characteristic (ROC) curve of relevant factors for the diagnosis and prediction of rotator cuff tear was analyzed. Results:Univariate analysis showed that age, angle of humeral greater tuberosity and notch angle of humeral greater tuberosity related to rotator cuff tear (all P<0.05). On the contrary, gender, history of hypertension, history of smoking, history of diabetes and BMI were not correlated with rotator cuff tear (all P>0.05). Multivariate Logistic regression analysis showed significant correlations of angle of humeral greater tuberosity and notch angle of humeral greater tuberosity with rotator cuff tear (all P<0.05). Spearman correlation analysis showed that age was not correlated with angle of humeral greater tuberosity and notch angle of humeral greater tuberosity ( r=0.09, 0.13, all P>0.05), but there was significant positive correlation between angle of humeral greater tuberosity and notch angle of humeral greater tuberosity ( r=0.76, P<0.01). When the optimal cutoff values of angle of humeral greater tuberosity and notch angle of humeral greater tuberosity were 70.05° and 150.55°, the area under the ROC curve (AUC) for predicting rotator cuff tear was 0.79 (95% CI 0.71-0.87, P<0.01) and 0.81 (95% CI 0.74- 0.89, P<0.01). Conclusions:Angle of humeral greater tuberosity and notch angle of humeral greater tuberosity are independent factors for rotator cuff tear, and larger angles suggest higher prevalence of rotator cuff tear. Besides, the notch angle of humeral greater tuberosity has relatively better predictive performance.
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The anterior cruciate ligament (ACL) injury is a common sports injury that has a significant impact on knee function and patients′ mobility. With the popularity of national fitness campaign in China, the incidence of ACL injury is increasing year by year. Currently, there still lacks clinical standards or guidelines on how to choose appropriate treatment methods, surgical plans and rehabilitation protocols for ACL injury. In order to timely reflect the new treatment concept of ACL injury, standardize its diagnosis and treatment and improve the curative effect, the Sports Medicine Society of Chinese Research Hospital Association and the Editorial Board of Chinese Journal of Trauma organized domestic orthopedic and sports medicine experts to formulate the "clinical evidence-based guideline for the diagnosis and treatment of anterior cruciate ligament injury (2022 version)" based on the level of evidence-based medicine and in compliance with the principle of scientificity, practicability and advancement. The present guideline includes 12 recommendations for the diagnosis, treatment and rehabilitation of ACL injury in order to provide guidance and assistance for the clinical diagnosis and treatment of ACL injury in China.
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Objective:To explore the key pathways and genes involved in microglia inflammation through transcriptome sequencing and bioinformatics analysis.Methods:BV2 cells were stimulated by lipopolysaccharide to establish microglia inflammation model. The levels of IL-6 and TNF-α were detected by ELISA and RT-qPCR. The established microglia inflammation model was sequenced by transcriptome sequencing, and the differentially expressed genes were screened by bioinformatics method. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes were performed. The protein-protein interaction network of differentially expressed genes was constructed by using string database, and the protein-protein interaction network was visualized by using Cytoscape software. The protein interaction network module was extracted by using MCODE app. The hub gene was extracted by using cytohubba app and was verified through RT-qPCR. We conducted enrichment analysis of hub genes, predicted their targeted miRNAs and interacting drugs.Results:The microglia inflammation model was successfully established and verified by ELISA and RT-qPCR. We screened 434 differentially expressed genes by bioinformatics analysis of transcriptome sequencing results. GO analysis showed that these differentially expressed genes were mainly concentrated in cellular response to cytokine stimulus, inflammatory response, regulation of response to external stimulation. KEGG analysis showed that these differentially expressed genes were mainly concentrated in Chemokine signaling pathway, TNF signaling pathway, IL-17 signaling pathway. We constructed the protein interaction network of these differentially expressed genes, and carried out module analysis and extraction of hub genes. Most of hub genes are located in module 1, and the seed gene of module 1 is S1pr1. Hub genes include S1pr1, Cxcr4, Cx3cl1, Cx3cr1, Cxcl10, Cxcl2, Ccl4, Ccl5, Ccl9, Fpr1. RT-qPCR results showed that compared with the culture medium group, the mRNA expressions of S1pr1, Cxcr4, Cx3cl1 and Cx3cr1 were down-regulated, and the mRNA expressions of Cxcl10, Cxcl2, Ccl4, Ccl5, Ccl9 and Fpr1 were up-regulated in the LPS group. The enrichment analysis of hub genes mainly focused on chemokine-mediated signaling pathway, Class A/1 (Rhodopsin-like receptors), cell chemotaxis and so on. Drugs and miRNAs that may interact with hub genes were predicted. Conclusion:Through transcriptome sequencing and bioinformatics analysis of microglia inflammation model, differentially expressed genes were screened, hub genes and seed genes were extracted, which will help us further understand the molecular mechanism of microglia inflammation and provide potential targets for the treatment of related diseases.
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Osteoarthritis (OA), a chronic joint degenerative disease, is the significant cause of the loss of joint function in middle-aged and older people. Bone destruction, synovial hyperplasia, osteophyte formation, and subchondral bone sclerosis are the main features of osteoarthritis, and the typical symptom is severe joint pain. Consequent to unprecedented global population aging, osteoarthritis remains a leading cause of disability, and the treatment often comes at a high cost. With an in-depth understanding of related research, osteoarthritis is proven to be a multifactorial disease whose onset is not simply a cartilage lesion, and the immune plays an essential role in the development of the disease. Some studies proposed that chondrocytes are capable of altering gene expression and mediating osteoarthritis progression by regulating immune responses. Previous studies showed that the extent of immune dysregulation significantly correlates with the severity of osteoarthritis, revealing an association between immunity response and clinical manifestations. The study of immune infiltration, genetic alterations, and pathogenesis of osteoarthritis may provide new perspectives and methods for the treatment of osteoarthritis in the future. Therefore, this review, combined with the recent decade of literature, provides an overview of the research progress of the main immune cells and related cytokines in OA, which may provide a new direction of thinking for diagnosing and preventing this disease.
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Objective:To explore the clinical effectiveness of arthroscopic treatment of tibial eminence avulsion fracture by four-point fixation with suture anchors.Methods:A retrospective analysis was performed of the 58 patients with tibial eminence avulsion fracture who had been treated by the same group of surgeons using four-point fixation technique with suture anchors under arthroscopy at Department of Sports Medicine, The Affiliated Hospital to Qingdao University from January 2015 to December 2018. They were 33 males and 25 females, with an average age of 18.4 years (from 14 to 32 years). By the modified Meyers-McKeever classification, 15 fractures were type Ⅱ, 19 type Ⅲ and 24 type Ⅳ. Recorded and compared were knee Lysholm scores, International Knee Documentation Committee (IKDC) scores and tibial eminence height between preoperation and one year postoperation; recorded at the last follow-up were range of knee motion and results of Lachman and pivot-shift tests.Results:The 58 patients were followed up for a mean of 20.7 months (from 12 to 33 months). Bony union was achieved in all patients within 12 weeks after operation. In this cohort, the Lysholm score (85.2±4.9) and IKDC score (86.2±4.3) at one year postoperation were significantly higher than the preoperative values (43.2±5.2 and 51.2±4.9), and the post-operative tibial eminence height [(9.1±1.2) mm] was significantly lower than the preoperative value [(12.6±1.2) mm] (all P<0.05). The correlation coefficients between the tibial eminence height and the Lysholm & IKDC scores at one year postoperation were -0.16 and -0.17, respectively. The last follow-up showed a 132°±5° range of knee motion for all patients, a positive result of pivot-shift test (grade Ⅱ) for 3 and a positive result of Lachman test (grade Ⅰ) for 2. Conclusion:Arthroscopic treatment of tibial eminence avulsion fracture by four-point fixation with suture anchors can lead to satisfactory effectiveness, showing advantages of minimal invasion, anatomic reduction, reliable fixation, and little impact on the epiphysis plate.
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Tibial plateau fracture is a common acute trauma of the knee joint. At present, there are many studies on its classification and treatment, and minimally invasive treatment has become a research hotspot and mainstream direction of tibial plateau fracture. We summarized the clinical results of minimally invasive treatment of more than 300 cases of tibial plateau fractures, and proposed the concept of core weight-bearing area on tibial plateau, that is, the core weight-bearing area of the tibial plateau of the knee joint under normal motion statuswhile walking and moderate-intensity running. We performed thinsection CT scanning of the knee joint in a male volunteer for three-dimension finite element modeling.The results showed that during the walking state (the load was twice that of gravity), the core weight-bearing area of the medial and lateral plateaus was 389 mm 2 and 363 mm 2, accounting for 33.2% and 42.9% of tibial plateau, respectively;during the moderate-intensity running state (the load was four times that of gravity), the core weight-bearing area of the medial and lateral plateaus was 418 mm 2 and 406 mm 2, accounting for 35.6% and 48.0%of tibial plateau, respectively. Accordingly, tibial plateau fractures are supposed to be divided into core weight-bearing fracture and non-core weight-bearing fracture, and there are significant differences in the treatment ofthese twokinds of fractures: reduction is more demanding for core weight-bearing fracture,and the fracture involves the core area closely, the anatomical reduction is sought; for non-core weight-bearing area, the reduction requirements can be appropriately low demanded, and even in some cases , for example simple avulsion fracture, marginal fracture, some tibial plateau Hoffa fractures,can be treated conservatively. In summary, during clinical diagnosis and treatmentpractice, orthopedic surgeons should take the core weight-bearing area fracture as the core of diagnosis and treatment, strictly evaluate the extent of fracture involvement, select targeted internal fixation materials, and target to promote more accurate, minimally invasive, and individualized treatment of tibial plateau fractures.
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Objective:To investigate the repair effects and mechanism of mesenchymal stem cell osteogenesis-derived exosomes deliver miRNA-222-5p on tendon cell injury.Methods:Mesenchymal stem cell exosomes were collected, isolated and characterized. The mice achilles tendon was collected after cutting one week later. The tendon cells were isolated and cultured to obtain a tendon cell injury model (injury group). The subjects were divided into three groups. During the process of osteogenic differentiation, mesenchymal stem cells were co-cultured with tendon cells (co-culture group). Further, miRNA-222-5p mimics were transfected into mesenchymal stem cells, the co-cultured mesenchymal stem cells and tendon cells during the process of osteogenic differentiation (miRNA-222-5p group). Clone formation and Transwell were used to detect the ability of mesenchymal stem cells to secrete exosomes and exosomes transported miRNA-222-5p to repair damaged tendon cells. qPCR, Western-blot and fluorescence staining were used to detect the expression levels of cartilage-related proteins and bone-related proteins on mRNA and protein. Western-blot was used to detect the expression of signal pathway factors.Results:The shape of the exosomes was a typical cup - like structure. The exosome proteins marker was all expressed positively ( P<0.05). After counting the colony formation and Transwell test, the number of cell communities and cell invasion were significantly increased in the co-culture group compared with those in the injury group. The number of those in miRNA-222-5p group were significantly increased compared with those in co-culture group ( P<0.05). The qPCR, Western-blot and fluorescent staining test results showed that the mRNA and protein expression levels of SOX-9, COL2A1, ACAN, BMP2, Runx2, and OPN in the co-culture group were significantly increased compared with the injury group. The mRNA and protein expression levels of the above proteins in the miRNA-222-5p group were significantly increased compared with those in co-culture group ( P<0.05). We also detected the protein expression levels of signal pathway related factors. Western-blot results showed that the expression levels of NF-κB, Erk2, STAT3, STAT5 and Smad2 in the co-culture group were significantly increased compared with those in the injury group. The expression levels of the above factors in the miRNA-222-5p group were significant increased compared with the co-culture group ( P<0.05). Conclusion:The co-culture of mesenchymal stem cells and achilles tendon cells could promote the osteogenic differentiation of achilles tendon cells. Exosomes derived from mesenchymal stem cells could further promote the osteogenic differentiation of achilles tendon cells by transporting miRNA-222-5p. The mechanism may be related to the up-regulation of signal pathway factors in injured tendons, including NF-κB, Erk2, STAT3, STAT5 and Smad2.
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Tendon injuries often need surgical treatment, which enables to repair the structure and stability of the tendons to a certain extent, whereas it is difficult to restore to their normal strength. The primary reason is that the natural healing ability of tendons is limited and the functions of the repaired tendons cannot be restored completely. As further researches on tendon healing are conducted, biological technology provides a novel orientation for tendon repair. One of the research hotspots of tendon repair currently is to facilitate tendon healing using biological auxiliaries, including tendon stem /progenitor cells(TSPCs) and growth factors. The authors review the research progress in mechanism of TSPCs and growth factors accelerating tendon healing in order to provide a reference for the biological treatment of tendon injuries.
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Objective:To investigate the repair effect of electrospun gelatin polycaprolactone (GT/PCL) nanofiber aerogels (NFA) combined with cartilage extracellular matrix (ECM) for treatment of cartilage injuries in rabbits.Methods:Firstly, the GT/PCL electrospun membrane was prepared by electrospinning and was ground into the short fiber at high speed. ECM was extracted and separated from fresh bovine articular cartilage, which mixed with the short fiber solution (10 ∶1). Subsequently, it was used to prepared GT/PCL/ECM (NFA) three-dimensional scaffold. Finally, the physical characteristics of the three different scaffolds (GT/PCL, ECM and GT/PCL/ECM) were detected by scanning electron microscope and Fourier-transform infrared (FTIR) spectrometer, including the composition, microstructure, swelling rate, porosity, compressive strength and degradation rates. And the biocompatibility research was getting on by co-culturing the scaffold with chondrocytes. Fifteen male New Zealand white rabbits were divided into blank control group (Group A, n=5), ECM group (group B, n=5) and composite scaffold(GT/PCL/ECM)group (Group C, n=5) according to the random number table. An injury model was established and three types of bio-scaffold materials were implanted into different groups. At 3 weeks, the cartilage repair was evaluated among groups by semi quantitative global MRI scoring system (WORMS). After the animals were killed, the knee joints of each group were scored by the international society for cartilage repair histological score (ICRs); the ICRs histological score was performedby HE staining and safranine green staining. Results:Three scaffolds showed a porous three-dimensional structure under the scanning electron microscope. FIRT showed that GT and PCL were introduced into the scaffolds successfully. The GT/PCL NAF was loose and unable to be characterized by materials science. The swelling rate of GT/PCL/ECM scaffold [(1, 092.0±32.2)%] was higher than that of ECM scaffold [(933.6±16.3)%] ( P<0.01). The porosity of GT/PCL/ECM scaffold [(92.3±2.3)%] was higher than that of ECM scaffold [(85.9±2.2)%] ( P<0.05). The compressive strength of ECM scaffold [(2.7±0.1)kPa] and of GT/PCL/ECM scaffold [(2.4±0.1)kPa] showed no statistical difference ( P>0.05). The degradation rate of ECM scaffold was higher than that of GT/PCL/ECM scaffold, but the difference was not statistically significant ( P>0.05). The cytotoxicity rating of GT/PCL/ECM scaffold was grade I, indicating that its biocompatibility was better. At 3 weeks, the MRI WORMS score in Group C [(49.0±11.4)points] was significantly higher than that in Group B [(40.0±6.7)points] and that in Group A [(24.0±6.5) points] ( P<0.05 or 0.01); the general ICRS score of group C was [(7.4±1.1) points], which was significantly higher than that of group B [(4.6±1.1)points] and group A [(3.0±1.2)points] ( P<0.01); The ICRS histological scores of group C and group B were [(6.8±0.8)points] and [(4.2±0.8)points] respectively compared with group A [(2.8±0.8)points] were significantly higher ( P<0.05 or 0.01). Conclusion:GT/PCL/ECM (NFA) scaffold has similar tissue structure to natural cartilage and is superior to traditional ECM scaffold in physical properties and biocompatibility, which provides a stable environment for chondrocyte adhesion and growth, promotes collagen regeneration, and thus accelerates the repair of cartilage injury.
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Objective:To investigate the effect and mechanism of exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSC) in repair of tendon injury in rats.Methods:The hUC-MSC were cultured and the surface markers were identified by flow cytometry. The cells were induced to differentiate into osteoblasts, chondroblasts and adipocytes using a specific media. Meanwhile, the exosomes were isolated from the cell supernatant using exosome separation columns, and were identified by transmission electron microscopy, PKH67 staining and Western blot. A total of 40 Wistar rats were used to establish the Achilles tendon injury model by surgical resection. The rats were divided into hUC-MSC group (Group A) (with 100 μg exosome injected at the injured site) and control group (Group B) (with 250 μl normal saline injected at the injured site) according to the random number table, with 20 rats per group. The expressions of transforming growth factor β (TGF-β), bone morphogenetic protein (BMP-2), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF-2), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the tendon tissues of both groups were detected using q-PCR, Western blot and immunofluorescence assay at 4 weeks following injection. The expression of collagen III in the injured tissues of both groups was detected by immunohiestochemistry.Results:The isolated and cultured hUC-MSC presented fusiform under an inverted microscope. After osteogenic differentiation, the cells exhibited a cube nodular structure, and the Alizarin red staining was positive. After adipogenic differentiation, the fat was observed inside the cells, which was red by oil red O staining. After chondroblast differentiation, the cells secreted a large amount of glycosaminoglycans, and a strong positive was revealed by Alisin blue staining. The hUC-MSC-derived exosomes showed round disc shape with a depressed internal structure under a transmission electron microscope, which was verified via PKH67 staining. The Western blot analysis showed high expressions of motility-related protein-1 (CD9) and lysosomal associated membrane protein 3 (CD63). The q-PCR test revealed that the mRNA expressions of TGF-β (4.887±0.767), BMP-2 (3.079±0.150), VEGF (3.108±0.508) and FGF-2 (4.211±0.522) in Group A were markedly higher than those in Group B (1.000±0.062, 0.918±0.129, 1.004±0.103, 1.010±0.169, respectively) ( P<0.01), and that the mRNA expression of IL-1β (0.697±0.037) and TNF-α (0.793±0.021) in Group A was markedly lower than those in Group B (1.004±0.089 and 1.006±0.015, respectively) ( P<0.01). The Western blot analysis revealed that the protein expressions of TGF-β (1.434±0.041), BMP-2 (1.798±0.177), VEGF (1.552±0.113) and FGF-2 (1.357±0.039) in Group A were markedly higher than those in Group B (1.002±0.032, 0.992±0.068, 1.007±0.070, 0.994±0.051) ( P<0.01), and that the protein expressions of IL-1β (0.705±0.016) and TNF-α (0.840±0.045) in Group A was markedly lower than those in Group B (1.000±0.016, 1.003±0.040) ( P<0.01). The immunofluorescence revealed that the positive expression rates of TGF-β and VEGF in Group A were not significantly different from those in Group B ( P>0.05). However, the positive expression rates of BMP-2 (2.278±0.208) and FGF-2 (4.656±0.106) in Group A were markedly higher than those in Group B (0.315±0.101, 1.661±0.110) ( P<0.05 or 0.01), and the positive expression rates of IL-1β (1.677±0.947) and TNF-α (1.520±0.088) in Group A were greatly lower than those in Group B (4.296±0.291, 2.373±0.273, respectively) ( P<0.01). In Group A, the tendon collagen fibers were arranged regularly and tightly, with relatively significant expression of collagen III; while the tendon collagen fibers in Group B were distributed loosely, accompanying broken scarlike healing. Conclusion:The hUC-MSC-derived exosomes can prompt the repair of the injured tendon tissues, which may be associated with the function in up-regulating the expressions of growth factors including TGF-β, BMP-2, VEGF and FGF-2, enhancing the expression of collagen III and inhibiting the expression of the inflammatory cytokines including IL-1β and TNF-α.
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Objective:To investigate the effects and mechanism of exosomes secreted by human umbilical cord-derived mesenchymal stem cells （hUC-MSCs） in repair of tendon cell injury.Methods:The hUC-MSCs which were stably subcultured were isolated and purified by a tissue block adherent method，and the immunophenotype of hUC-MSCs was detected by flow cytometry. The induction media was employed to induce the differentiation of hUC-MSCs to osteoblasts，chondroblasts and adipocytes，and cell identification was performed subsequently. The secreted exosomes of MSCs （MSCs-exosomes） were extracted using an ultracentrifugation method. The exosomes were detected by Western blot and electron microscopy，and the fusion ability of the exosome membrane was detected by PKH67 staining fluorescence. Forty Wistar rats were divided into tendon injury group （ n = 20） and normal group （ n = 20） according to the random number table. In tendon injury group，the rats were sacrificed with 100 mg/kg pentobarbital sodium one week after Achilles tendon transection，and the injured tendon cells were obtained following digestion of the Achilles tendon. In normal group，the rats were sacrificed without any treatment and the normal tendon cells were obtained concurrently. After the exosomes were co-cultured with tendon cells in vitro for 12，24，48，72 hours，the proliferation of tendon cells was detected by CCK-8 assay. After the tendon cells were treated with hUC-MSCs exosomes for 24 hours，the effects of exosomes on transforming growth factor β （TGF-β），bone morphogenetic protein （BMP），vascular endothelial growth factor （VEGF），fibroblast growth factor （FGF），interleukin（IL）-1β and tumor necrosis factor-α （TNF-α） were detected by Western blot，qPCR and immunofluorescence. Results:The hUC-MSCs were identified and hUC-MSCs-exosomes were isolated successfully. The cultured MSCs were fusiform and positive for Alanine aminopeptidase （CD13），integrin β-1 （CD29），ECTO-5'-nucleotidase （CD73），thymocyte surface antigen （CD90） and endothelin （CD105），but negative for human leukocyte DR antigen （HLA-DR），hematopoietic progenitor cell antigen （CD34） and leukocyte common antigen （CD45）. The exosomes isolated showed a round disc shape and a diameter of 30-100 nm with a depressed internal structure under the electron microscope which was verified via PKH67 staining and the motility-related protein-1 （CD9） and lysosomal associated membrane protein 3 （CD63） were highly expressed. The CCK-8 assay showed the cell viability in tendon injury group was markedly higher than that in normal group at 12 h，24 h，48 h，and 72 h following treatment of tendon cells （ P < 0.01）. The results of qPCR revealed that the mRNA expressions of TGF-β （1.850 ± 0.127），BMP （2.133 ± 0.398），FGF （1.610 ± 0.223） and VEGF （2.207 ± 0.059） in tendon injury group were markedly higher than those in normal group（1.004 ± 0.105，1.007 ± 0.145，1.007 ± 0.140，1.001 ± 0.065，respectively） （ P < 0.05）. However，the mRNA expressions of IL-1β （0.102 ± 0.009） and TNF-α （0.130 ± 0.013） in tendon injury group was markedly lower than those in normal group （1.004 ± 0.113，1.006 ± 0.134） （ P < 0.01）. The results of Western blot were consistent with those of qPCR. Conclusions:The exosomes secreted by hUC-MSCs can promote the growth of tendon cells and repair of tendon cell injury by up-regulating the expression of growth factors TGF-β，BMP，VEGF and FGF，and inhibiting the expression of inflammatory factors IL-1β and TNF-α.
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Objective:To compare the clinical prognosis of modified and traditional knotless suture bridge technique in treatment of rotator cuff tear under shoulder arthroscopy.Methods:A retrospective case-control study was conducted to analyze 60 patients with rotator cuff tear admitted to Affiliated Hospital of Qingdao University from June 2018 to June 2019，including 19 males and 41 females，aged 32-74 years［（59.3±10.1）years］. There were 26 patients on the left side and 34 patients on the right side，with the body mass index（BMI）of 19.5-32.4 kg/m 2［（25.5±2.6）kg/m 2］，rotator cuff tear of 2.0-3.7 cm［（2.7±0.4）cm］and pain duration of 2-88 days［（26.2±17.1）days］. A total of 31 patients were repaired with a modified knotless suture bridge（modified group）and 29 patients with a traditional knotless suture bridge（traditional group）. Comparison was made between the two groups in aspects of range of motion of shoulder flexion，abduction and external rotation，visual analog scale（VAS），University of California Los Angeles（UCLA）should function score，Constant shoulder function score，retear and complications at postoperative 3 and 12 months. Results:All patients were followed up for 9-15 months［（12.0±1.8）months］. Three months after operation，the two groups showed no significant differences in shoulder range of motion of abduction，flexion，external rotation，UCLA shoulder function score or Constant shoulder function score（ P>0.05）；while VAS was（2.7±1.2）points in modified group，significantly lower than（3.4±1.2）points in traditional group（ P<0.05）. Twelve months after operation，the shoulder range of motion of abduction and flexion in modified group was（146.9±21.4）° and（150.4±16.2）°，significantly higher than that in traditional group［（130.7±27.4）°，（140.6±18.4）°］（ P<0.05）；There was no significant difference in external rotation activity between the two groups（ P>0.05）；VAS，UCLA shoulder function score and Constant shoulder function score［（1.2±0.5）points，（29.5±2.3）points，（80.4±5.4）points，respectively］in modified group were significantly higher than those in traditional group［（1.5±0.5）points，（27.2±2.7）points，（76.3±6.6）points，respectively］（ P<0.05）. Three months after operation，there was no significant difference in the classification of Sugaya between the two groups（ P>0.05）. Twelve months after operation，the classification of Sugaya was significantly different between the two groups（ P<0.05），with no retear in modified group but 3 patients with retear in traditional group. No postoperative complications occurred，such as non-healing，infection or persistent swelling. Conclusion:For patients with rotator cuff tear，the modified knotless suture bridge technique under shoulder arthroscopy has better range of motion and function，more obvious pain relief and a lower rate of retear than the traditional technique.