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Resumen Introducción : Las lesiones osteocondrales de rodilla son una afección frecuente en jóvenes. Los trasplantes alogénicos usando injerto congelado se presentan como una opción de tratamiento en pacientes con lesiones grandes o sin zona dadora. Este trabajo buscó analizar retrospectivamente los resultados funcionales y la tasa de falla de los trasplantes osteocondrales con injerto cadavérico congelado. Métodos : Se incluyeron pacientes sometidos a tras plantes osteocondrales de rodilla con injerto cadavérico congelado en nuestra institución, entre 2014 y 2019, con dos años de seguimiento mínimo. Variables evaluadas: edad al momento de la intervención, escalas funciona les International Knee Documentation Committee (IKDC) y Lysholm pre y post operatorios, complicaciones y tasa de falla. Resultados : Incluimos 25 pacientes. La edad media fue de 43.5 años (RIQ 29-50), 45% fueron mujeres y el seguimiento promedio fue de 83 meses (DS 54.6). El ta maño promedio del defecto osteocondral fue de 4 cm2. La escala de Lysholm promedio pre y postoperatorio fue de 39 (DS 19.3) y 82 (DS 15.4) respectivamente (p < 0.01). El IKDC promedio pre y postoperatorio fue de 42 (DS 13.8) y 60 (DS 13.5) respectivamente (p < 0.01). La tasa de falla fue del 20% (n=5). Discusión : Los pacientes presentaron una mejoría postoperatoria evidenciada en los resultados funcio nales, y una tasa de falla del 20%. El uso de trasplante osteocondral congelado se presenta como un recurso útil para el tratamiento de lesiones condrales graves.
Abstract Introduction : Knee osteochondral lesions represent a frequent pathology within young active patients. One possible indication for severe lesions or in case of im possibility of harvesting an autograft is the use of fresh frozen allograft. The objective of this study was to ret rospectively analyze functional results and failure rate after osteochondral transplants using fresh frozen al lografts. Methods : We analyzed data from patients who under went knee osteochondral transplant using mosaicplasty technique with fresh frozen allografts at our institution between 2014 and 2019. We included those patients with at least two-year follow-up. Demographic characteristics such as age at the moment of intervention and size of the defect were included. Functional results were assessed using pre and postoperative Lysholm and IKDC scores. Patients who underwent a knee replacement were considered failures. Results : Twenty-five patients were included. The me dian age was 43.5 years (IQR 29-50), 45% were female and the mean follow-up was 83 months (SD 54.6). Mean osteochondral defect size was 4 cm2. Mean pre and post operative Lysholm scores were 39 (SD 19.3) and 82 (SD 15.4) respectively (p < 0.01). Mean pre and postoperative IKDC scores were 42 (SD 13.8) and 60 (SD 13.5) respec tively (p < 0.01). Five patients (20%) underwent a knee replacement afterwards and were considered failures. Discussion : Our results after a mean seven-year follow-up evidenced an overall improvement in func tional scores and a failure rate of 20%. Osteochondral transplant using fresh frozen allografts is a reliable and feasible treatment for patients with large osteochondral defects.
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La artrosis de rodilla grado 1 es un problema frecuente a escala mundial. La fisioterapia se presenta como una alternativa prometedora para el tratamiento conservador de esta patología, ya que reduce eficazmente la artralgia. Objetivo. Describir la eficacia de los ejercicios terapéuticos para aliviar el dolor en la artrosis de rodilla grado I. Metodología. Se trata de una revisión sistemática, que abarcó una búsqueda exhaustiva en varias bases de datos como Pubmed, Scielo y Elsevier. Los criterios de búsqueda incluyeron ensayos de control aleatorios, experimentales y cuasiexperimentales realizados entre los años 2017 y 2023. Resultados. De un total de 82 documentos se excluyeron 40 al ser estudios secundarios. Posteriormente, se excluyeron 21 estudios adicionales debido a la escasa relación entre las variables del estudio y a su falta de disponibilidad. Finalmente, se seleccionaron 21 artículos que cumplieron con los criterios de evaluación de calidad metodológica mediante la escala CRF-QS. Para evaluar el dolor, la rigidez, la funcionalidad y la calidad de vida, se utilizaron escalas como EVA, NPRS, WOMAC y OXFORD. Los ejercicios isocinéticos resultaron ser los más efectivos, ya que demostraron un aumento de la fuerza y el grosor del cartílago articular, lo que resultó en una disminución de las puntuaciones de EVA de 8,05 a 3,75. Conclusión. El ejercicio terapéutico supervisado centrado en el fortalecimiento de las extremidades inferiores ha demostrado ser una alternativa efectiva para el tratamiento conservador de la artrosis de rodilla grado I. Este enfoque alivia eficazmente el dolor, mejora la calidad de vida e incluso puede detener la progresión de la enfermedad.
Grade 1 knee osteoarthritis is a common problem worldwide. Physiotherapy is presented as a promising alternative for the conservative treatment of this pathology, since it effectively reduces arthralgia. Aim. To describe the effectiveness of therapeutic exercises to relieve pain in grade I knee osteoarthritis. Methodology. This is a systematic review, which included an exhaustive search in several databases such as Pubmed, Scielo and Elsevier. Search criteria included randomized, experimental and quasi-experimental control trials conducted between the years 2017 and 2023. Results. Of a total of 82 documents, 40 were excluded as they were secondary studies. Subsequently, 21 additional studies were excluded due to poor relationships between study variables and lack of availability. Finally, 21 articles were selected that met the methodological quality evaluation criteria using the CRF-QS scale. To evaluate pain, stiffness, functionality and quality of life, scales such as VAS, NPRS, WOMAC and OXFORD were used. Isokinetic exercises were found to be the most effective, demonstrating an increase in articular cartilage strength and thickness, resulting in a decrease in VAS scores from 8.05 to 3.75. Conclusion. Supervised therapeutic exercise focused on strengthening the lower extremities has been shown to be an effective alternative to the conservative treatment of grade I knee osteoarthritis. This approach effectively relieves pain, improves quality of life, and may even stop the progression of osteoarthritis. disease.
A osteoartrite do joelho grau 1 é um problema comum em todo o mundo. A fisioterapia apresenta-se como uma alternativa promissora para o tratamento conservador desta patologia, uma vez que reduz eficazmente a artralgia. Mirar. Descrever a eficácia dos exercícios terapêuticos no alívio da dor na osteoartrite de joelho grau I. Metodologia. Trata-se de uma revisão sistemática, que incluiu uma busca exaustiva em diversas bases de dados como Pubmed, Scielo e Elsevier. Os critérios de pesquisa incluíram ensaios de controle randomizados, experimentais e quase-experimentais realizados entre os anos de 2017 e 2023. Resultados. De um total de 82 documentos, 40 foram excluídos por se tratarem de estudos secundários. Posteriormente, 21 estudos adicionais foram excluídos devido às más relações entre as variáveis do estudo e à falta de disponibilidade. Por fim, foram selecionados 21 artigos que atenderam aos critérios de avaliação da qualidade metodológica pela escala CRF-QS. Para avaliar dor, rigidez, funcionalidade e qualidade de vida foram utilizadas escalas como VAS, NPRS, WOMAC e OXFORD. Os exercícios isocinéticos foram considerados os mais eficazes, demonstrando um aumento na força e espessura da cartilagem articular, resultando em uma diminuição nos escores VAS de 8,05 para 3,75. Conclusão. O exercício terapêutico supervisionado focado no fortalecimento das extremidades inferiores tem se mostrado uma alternativa eficaz ao tratamento conservador da osteoartrite do joelho grau I. Esta abordagem alivia eficazmente a dor, melhora a qualidade de vida e pode até interromper a progressão da osteoartrite.
Subject(s)
Osteoarthritis, Knee摘要
Objective To detect the changes of mitophagy level in rats with endplate cartilage degeneration induced by spinal instability,and explore the role of PINK1/Parkin-mediated mitophagy in endplate cartilage and intervertebral disc degeneration.Methods The rat spinal instability model was established by surgically removing the superspinal and interspinal ligaments of L2 to L5,and cleaning the bilateral articular processes of the L2 to L5.Eighteen SD rats were divided into the normal group,the degenerative group,and the carbonyl cyanide 3-chlorophenylhydrazone(CCCP)group,with 6 rats in each group.The rats in the normal group had no special treatment,the rats in the degenerative group constructed a rat spinal instability model,and the rats in the CCCP group were injected with 5 μL of CCCP(10 μmol/L)in the intervertebral disc after the construction of spinal instability model.The changes of histomorphology in the endplate cartilage and intervertebral disc were abserved by HE staining,and the change of extracellular matrix of endplate cartilage was observed by safranin O-fast green staining.RT-PCR detected the mRNA expression of type Ⅱ collagen(COL-2A),aggrecan(ACAN),PINK1 and Parkin in each group.The changes of the protein expression levels of COL-2A,ACAN,PINK1,Parkin and mitochondrial membrane proteins of Tomm20 and Timm23 were detected by Western blot.Results Compared with the normal group,the intervertebral disc nucleus pulposus of rats in the degenerative group was significantly destroyed and the secretion of extracellular matrix of endplate chondrocytes decreased;while the structure of intervertebral discs for rats in the CCCP group was more intact,and the secretion of extracellular matrix of endplate chondrocytes was significantly increased compared with that in the degenerative group.Compared with the normal group,the expression of COL-2A and ACAN in endplate cartilage tissues of rats in the degenerative group were significantly down-regulated(P<0.05),the expression of mitochon-drial autophagy-related genes of PINK1 and Parkin were significantly decreased(P<0.05),and the expression of mitochondrial membrane proteins of Tomm20 and Timm23 were increased(P<0.05).Compared with the degenerative group,the expression of COL-2A,ACAN,PINKI and Parkin in the endplate cartilage tissue of rats in the CCCP group were significantly up-regulated(P<0.05),and the protein levels of Tomm20 and Timm23 were significantly down-regulated(P<0.05).Conclusion Rat spinal instability leads to a decrease level of mitophagy mediated by PINK1/Parkin signaling pathway in endplate cartilage,thereby inducing endplate cartilage and intervertebral disc degeneration,and the activation of mitophagy can significantly reduce endplate cartilage and intervertebral disc degeneration.
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OBJECTIVE@#To investigate the effectiveness of comprehensive rhinoplasty with autogenous costal cartilage grafting and prosthesis augmentation rhinoplasty in the treatment of secondary nasal deformity with saddle nasal deformity after cleft lip surgery.@*METHODS@#The clinical data of 96 patients with secondary nasal deformity with saddle nasal deformity after cleft lip surgery between September 2008 and January 2019 were retrospectively analyzed. There were 17 males and 79 females with an average age of 25.6 years (range, 17-38 years). Autogenous costal cartilage grafts were used to construct stable nasal tip framework and enhance the strength of alar cartilage. Nasal dorsum prostheses (39 cases of bulge, 45 cases of silicone prosthesis) or autogenous costal cartilage (12 cases) were used for comprehensive rhinoplasty. Visual analogue scale (VAS) score was used to evaluate the postoperative satisfaction subjectively, and nasal alar height symmetry index, nasal alar width symmetry index, nasal dorsum central axis deviation angle, and nasal columella deviation angle were calculated to evaluate objectively before and after operation.@*RESULTS@#All patients were followed up 6 months to 8 years, with an average of 13.4 months. Nasal septal hematoma occurred in 3 patients after operation, which was improved after local aspiration and nasal pressure packing. Two cases had mild deformation of the rib cartilage graft of the nasal dorsum, one of which had no obvious deviation of the nasal dorsum and was not given special treatment, and one case underwent the cartilage graft of the nasal dorsum removed and replaced with silicone prosthesis. The incisions of the other patients healed by first intention, and there was no complication such as postoperative infection and prosthesis displacement. The nasal alar height symmetry index, nasal alar width symmetry index, nasal dorsum central axis deviation angle, and nasal columella deviation angle significantly improved after operation when compared with preoperative ones ( P<0.05). Postoperative subjective satisfaction evaluation reached the level of basic satisfaction or above, and most of them were very satisfied.@*CONCLUSION@#Comprehensive rhinoplasty using autologous rib cartilage grafting to construct a stable nasal tip support, combined with dorsal nasal prosthesis or autologous cartilage implantation, can achieve good effectiveness on secondary nasal deformity with saddle nasal deformity after cleft lip surgery.
Subject(s)
Male , Female , Humans , Adult , Rhinoplasty , Cleft Lip/surgery , Retrospective Studies , Nose/surgery , Nasal Septum/surgery , Nasal Cartilages/surgery , Silicones , Treatment Outcome摘要
ObjectiveThis study aims to explore the potential mechanism of Danggui Niantongtang in treating knee osteoarthritis （KOA） by regulating the intestinal flora through 16S rDNA analysis. MethodThirty-six C57BL/6J mice were subjected to anterior cruciate ligament transection （ACLT） to establish a KOA model and were randomly divided into the sham surgery group， model group， low-dose Danggui Niantongtang group （0.819 g·kg-1）， medium-dose Danggui Niantongtang group （1.638 g·kg-1）， high-dose Danggui Niantongtang group （3.276 g·kg-1）， and Meloxicam group （0.975 mg·kg-1）， with 6 mice in each group. Except for the treatment groups， the sham surgery group and model group were given normal saline by gavage. After 4 weeks of continuous intervention， feces and intact knee joints of the mice were collected. Hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining were performed to observe the pathological changes in knee joint tissue morphology. The 16S rDNA sequencing was used to analyze changes in the abundance and diversity of intestinal microorganisms before and after treatment， along with corresponding functional predictions. ResultHigh-dose Danggui Niantongtang and Meloxicam significantly relieved pain symptoms in KOA mice， improved the disorder of joint structure， maintained the integrity of knee articular cartilage， increased the expression of type Ⅱ collagen alpha 1 （Col2a1） in articular cartilage， and decreased the expression of matrix metalloproteinase-13 （MMP-13）. The results of 16S rDNA sequencing showed that high-dose Danggui Niantongtang could adjust the abundance and structure of intestinal microbial species. Compared with the sham surgery group， the abundance of Proteobacteria， Actinobacteria， Ruminococcus， and Bacteroides was significantly increased in the model group （P<0.05）， while in the Danggui Niantongtang group， the abundance of these four flora was significantly reduced compared with the model group. Compared with the sham surgery group， the abundance of Verrucomicrobia， Oscillospira， and Akkermansia was significantly decreased in the model group （P<0.05）， while in the Danggui Niantongtang groups， the abundance of these three flora was significantly increased compared with the model group （P<0.05）. Functional pathway prediction of differential genera revealed that species differences among groups mainly involved metabolic pathways with high abundance associated with biosynthesis and precursors， as well as energy production， including amino acid biosynthesis， nucleotide and nucleoside biosynthesis， cofactors， prosthetic groups， electron carriers， and vitamin biosynthesis. ConclusionDanggui Niantongtang can effectively protect articular cartilage and delay the progression of KOA， possibly by regulating the structure of the intestinal flora， promoting probiotics， and inhibiting the growth of harmful pathogenic bacteria.
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ObjectiveTo observe the effects of Xibining （XBN） and adipose stem cell exosome （ADSC-Exos） in the cases of separate or joint application on cartilage degeneration and mitochondrial autophagy and explore its mechanism of action to improve knee osteoarthritis （KOA）. MethodSD rats were divided into a sham operation group （sham group）， a model group， an ADSC-Exos group （Exos group）， an XBN group， and an ADSC-Exos+XBN group （Exos+XBN group）. KOA model was established by using anterior cruciate ligament transection （ACLT）. The pain sensitivity status of rats was evaluated， and the degeneration degree of the knee joint and cartilage tissue was detected by Micro-CT and pathological staining. The expression of p62 and LC3B was observed by immunofluorescence， and the serum levels of TNF-α， IL-1β， IL-6， and IL-15 in rats were detected by ELISA. The Western blot was used to detect the protein expression levels of MMP-3， MMP-13， ADAMTS5， ColⅡ， TIMP， ACAN， PINK1， Parkin， p62， and LC3A/B. ResultCompared with the sham group， rats in the model group showed decreased cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， varying degrees of abrasion and loss of cartilage tissue， degeneration of cartilage tissue， elevated serum IL-1β， IL-6， IL-15， and TNF-α levels （P<0.01）， and increased protein expression of MMP-3， MMP-13， and ADAMTS5 in cartilage tissue. In addition， the protein expression of ColⅡ， TIMP1， and ACAN was decreased （P<0.01）. Compared with the model group， rats in each treatment group showed higher cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， reduced cartilage tissue degeneration， lower serum levels of IL-1β， IL-6， IL-15， and TNF-α （P<0.05，P<0.01）， decreased protein expression of MMP-3， MMP-13， and ADAMTS5， and higher protein expression of Cold， TIMP1， and ACAN in cartilage tissue （P<0.05，P<0.01）. Moreover， the changes were the most obvious in the Exos+XBN group. ConclusionBoth ADSCs-Exos and XBN can increase the level of mitochondrial autophagy in chondrocytes and delay cartilage tissue degeneration by promoting the expression of the PINK1/Parkin signaling pathway， and the combination of the two can enhance the therapeutic effect.
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Objective:To discuss the repairment effect of intra-articular injection of adipose derived stem cells(ADSCs)on articular cartilage destruction in the temporomandibular joint osteoarthritis(TMJOA)model rabbits,and to clarify the possible mechanism.Methods:Twenty-seven rabbits were randomly divided into control group,model group,and ADSCs group.The ADSCs of the rabbits were extracted and cultured.The rabbit TMJOA model was prepared by monosodium-iodoacetate(MIA)injection technique.The temporomandibular joint cavity of the TMJOA model rabbits in ADSCs group was given two continuous intra-articular injections of 1.0×106 mL-1 ADSCs,while the rabbits in control and model group were given sequivalent volume of saline into the temporomandibular joint cavity.After 8 weeks,Micro-CT scan was performed on the temporomandibular joints of the rabbits in various groups;the bone volume fraction(BV/TV),bone surface area/bone volume(BS/BV),trabecular thickness(Tb.Th),trabecular separation(Tb.Sp),and trabecular number(Tb.N)of condyles tissue of the rabbits in various groups were analyzed;HE staining was used to observe the pathomorphology of condyles tissue of the rabbits in various groups;immunohistochemistry was used to detect the localization and expression levels of SRY-related high mobility group box gene 9(SOX9),matrix metalloproteinase-13(MMP-13),and vascular endothelial growth factor(VEGF)proteins in condyles tissue of the rabbits in various groups;Western blotting method was used to detect the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in various groups.Results:The micro-CT scan results showed that compared with control group,the BV/TV,Tb.Th,and Tb.N of condyles tissue of the rabbits in model group were significantly decreased(P<0.05),while the BS/BV and Tb.Sp were significantly increased(P<0.05);compared with model group,the BV/TV,Tb.Th,and Tb.N in condyles tissue of the rabbits in ADSCs group were significantly increased(P<0.05),and the BS/BV and Tb.Sp were significantly decreased(P<0.05).The HE staining results showed that the condylar cartilage surface of the rabbits in control group was smooth with clear layers and intact structure;compared with control group,the surface of condyles tissue of the rabbits in model group was irregular with thickened hypertrophic layer and areas of cell depletion and clustering;compared with model group,the pathological damage of condyles tissue of the rabbits in ADSCs group was significantly decreased.The immunohistochemical staining results showed that compared with control group and ADSCs group,the number of brown granule in condyles tissue of the rabbits in model group was increased,mainly concentrated in the hypertrophic layer,especially in the bone cartilage junction site and the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in model group were significantly increased(P<0.05);compared with model group,the number of brown granule in condyles tissue of the rabbits in ADSCs group was significantly decreased,and the expression levels of SOX9,MMP-13,and VEGF proteins were significantly decreased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in model group were significantly increased(P<0.05);compared with model group,the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in ADSCs group were significantly decreased(P<0.05).Conclusion:Intra-articular injection of ADSCs can effectively repair the cartilage destruction in TMJOA,alleviate the cartilage injury,and mitigate the progression of osteoarthritis.
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Objective:To explore a set of procedures for the effictive granulation of cartilage,and to construct injectable cartilage graft with platelet-rich gel(PRG),and to evaluate its effects in nude mice models.Methods:The costal cartilage of adult male rab-bits was cut into pieces and placed in a mortar for 30-60 s freezing in liquid nitrogen and grinding for a short time to obtain granular cartilage.Blood was collected from the middle ear artery and PRG was prepared by double centrifugation.Granular cartilage and the mixture of granular cartilage and PRG were injected subcutaneously in nude mice of control group(n=5)and experimental group(n=5)respectively.8 weeks after injection,the gross morphology observation and histological examination were pertormed.The nasal dor-sum augmentation model of nude mice was established in the experimental group.Results:The cartilage particles were in the size of 10-500 pm in diameter after frozen grinding,and injection could be realized.In vitro culture showed that the cell survival rate of granular cartilage reached to 80％.In vivo test showed that the sample morphology of the control group was insignificant,and the sur-face was grainy.That of the experimental group was well maintained,and the surface was smooth with obvious capillaries.The sam-ples of experimental group achieved significant augmentation in the nude mouse model of nasal dorsum augmentation.Conclusion:Freeze-milling technology can achieve efficient granulation of cartilage,and the graft constructed with PRG gel is suitable for maxillo-facial cartilage transplantation repair.
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BACKGROUND:Cartilage defects are one of the major clinical challenges faced by orthopedic surgeons.Tissue engineering is an interdisciplinary approach that combines knowledge of engineering and cell biology to provide new ideas and approaches for the repair of cartilage defects. OBJECTIVE:To prepare a multi-component composite scaffold based on silk fibroin,gelatin,and chitosan to screen for a three-dimensional porous scaffold suitable for cartilage regeneration by evaluating its physicochemical properties and biological performance. METHODS:Four groups of porous scaffolds were prepared by vacuum freeze-drying method using silk fibroin,gelatin and chitosan as the base materials,namely chitosan/gelatin scaffold,silk fibroin/chitosan scaffold,silk fibroin/gelatin scaffold and silk fibroin/chitosan/gelatin scaffold.The suitable cartilage scaffolds were screened by scanning electron microscopy,X-ray diffractometer,porosity,water absorption and swelling rate,biodegradation rate and mechanical property detection.Then cartilage scaffolds were co-cultured with chondrocytes isolated and extracted from patients with osteoarthritis.The feasibility of porous scaffolds for cartilage injury repair was evaluated in vitro by cell adhesion rate assay,cell live-dead staining and cell activity proliferation assay. RESULTS AND CONCLUSION:(1)All four groups of scaffolds had porous structures.The comprehensive physical performance test results showed that the silk fibroin/gelatin/chitosan scaffold was more in line with the requirements of cartilage defect repair.This scaffold had a pore size of(176.00±53.68)μm,the porosity of(80.15±2.57)%,and water absorption and swelling rate of(3 712±358)%.After immersion in PBS containing lysozyme for 28 days in vitro,the biodegradation rate was(46.87±3.25)%,and it had good mechanical properties.(2)Chondrocytes could adhere well on the silk fibroin/gelatin/chitosan scaffold,and the cell adhesion rate increased with time.CCK8 and live/dead cell double staining results showed that silk fibroin/gelatin/chitosan scaffold had good biocompatibility and low cytotoxicity.(3)The results showed that silk fibroin/gelatin/chitosan scaffold had a highly hydrated 3D structure,suitable pore size and porosity,good biodegradability and superior mechanical properties,which can provide a good reticular skeleton and microenvironment for nutrient transport and chondrocyte attachment and proliferation.
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BACKGROUND:Intra-articular injection played an important role in the treatment of osteoarthritis and has more options with the development of novel drug delivery systems.The cartilage targeting function is aimed at the adhesion or retention of drugs in the cartilage layer to form a drug bank to achieve slow release and precise drug delivery. OBJECTIVE:To review various cartilage targeting biomaterials and their characteristics in the treatment of osteoarthritis by articular injection. METHODS:Using the term"osteoarthritis,drug carrier,drug delivery,cartilage targeting,penetrate"as key words,relevant articles were searched in CNKI,WanFang and PubMed databases.According to inclusion and exclusion criteria,67 articles were finally selected for further review. RESULTS AND CONCLUSION:The research on cartilage-targeting biomaterials is mainly divided into two directions.One is the combination of electrostatic interaction,such as the combination of positively charged biomaterials and negatively charged polysaccharides in cartilage.This kind of scheme is operable and easy to modify,but limited by the shortcomings of electrostatic interaction itself,it performs badly in advanced osteoarthritis.Another one is the specific binding of various components in cartilage which is strong and reliable,and related biomaterials have excellent performance in advanced osteoarthritis,which is an important direction for future cartilage-targeted therapy.
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BACKGROUND:The combination of good biomechanical properties,controlled drug release and multi-functionality of core-shell structured nanofibers is receiving more and more attention,which also makes them promising for a wide range of applications in the field of oral tissue regeneration. OBJECTIVE:To summarize the preparation,drug loading and release mechanisms of core-shell structured nanofibers and their application in the regenerative repair of oral tissues. METHODS:A computer search of the literature collected in CNKI and PubMed from January 2000 to November 2022 was applied,and the search terms in English and Chinese were"electrospinning,core-shell structures,drug delivery systems,jaw bone regeneration,cartilage regeneration,periodontal tissue regeneration". RESULTS AND CONCLUSION:(1)There are various methods for the preparation of core-shell structured nanofibers,but the coaxial and emulsion methods of electrostatic spinning have unique advantages such as simple operation,diverse material selection and good biocompatibility.(2)Core-shell structured nanofibers can be used as bacteriostatic agents,carriers of different types of drugs,and scaffolds for cell adhesion,providing new therapeutic options for oral tissue regeneration.(3)Controlled degradation and drug release rate of core-shell structured nanofibers can better adapt to the healing process of oral tissue defect repair and achieve ideal tissue regeneration.
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BACKGROUND:In cartilage degeneration in osteoarthritis,cytokines and signaling pathways that target chondrocytes play an important role. OBJECTIVE:To review the latest research progress of osteoarthritis related cytokines and signaling pathways in recent years,such as the mechanism of action and treatment modalities,in order to provide a basis for future exploration of new therapeutic targets and modalities. METHODS:Literature search was conducted on CNKI,WanFang,VIP,PubMed,Web of Science,and Medline databases.Chinese search terms were"osteoarthritis,cytokines,signal pathway,chondrocyte,inflammation,treatment".Finally,60 papers were included for review. RESULTS AND CONCLUSION:(1)In current studies,it is believed that the specific mechanism of osteoarthritis is not clear,and a large number of studies have shown that osteoarthritis is strongly associated with cytokines and signaling pathways,which is a complex process of action.Relevant studies taking cytokines and signaling pathways as therapeutic breakthroughs are also the current hot spot.(2)The receptor antagonists of pro-inflammatory factors such as interleukin 1 are not effective in the treatment of osteoarthritis,and more studies turn to gene therapy.(3)The therapeutic methods of transforming growth factor β,recombinant factors of Wnt signaling pathway,gene therapy and mesenchymal stem cells have obtained positive research results.However,basic and clinical studies on safety and efficacy are likely to be conducted in future studies.(4)At present,relevant therapeutic methods such as platelet-rich plasma have been widely used in clinical practice,while recombinant factor,gene therapy and mesenchymal stem cell therapy are all in the research stage,among which mesenchymal stem cell therapy and gene therapy are expected to make breakthroughs in the field of cartilage repair and regeneration,and are worthy of expectation in the future.However,more clinical and basic studies are needed to verify its effectiveness and safety,explore its mechanism of action and scope of application,and set standards for its clinical use.
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BACKGROUND:There are many treatment methods for knee osteoarthritis,among which electroacupuncture,as an important non-drug treatment,is effective in the treatment of knee osteoarthritis,but its exact mechanism is not clear. OBJECTIVE:Effect of electroacupuncture on the expression of p53 and P21 in articular cartilage and subchondral bone of aged rats with knee osteoarthritis. METHODS:Eight 6-month-old male Sprague-Dawley rats were included in the young group and sixteen 24-month-old male Sprague-Dawley rats were randomly divided into old group(n=8)and electroacupuncture group(n=8).The rats in the electroacupuncture group received electroacupuncture stimulation once a day,5 days a week,for 8 continuous weeks,and the other two groups did not do any treatment.Eight weeks later,the level of type Ⅱ collagen C-terminal peptide in peripheral blood was detected by ELISA,the morphology of left knee cartilage and subchondral bone was observed by safranin O-fast green staining,the degree of knee cartilage degeneration was evaluated by modified Mankin's score,the microstructure of left knee cartilage and subchondral bone was detected by micro-CT,and the expression levels of matrix metalloproteinase 13,P53,P21 Mrna and protein were detected by RT-PCR and western blot respectively. RESULTS AND CONCLUSION:Compared with the young group,the level of C-terminal peptide of type Ⅱ collagen in the peripheral blood was increased in the old group(P<0.05).The micro-CT results showed that the bone volume fraction,bone mineral density and the number of bone trabeculae were decreased in the old group compared with the young group(P<0.05),while the trabecular separation increased(P<0.05).Safranin O-fast green staining showed that in the old group,the surface layer of cartilage was uneven with fissures,the morphology of chondrocytes was irregular and stained unevenly,the boundary between the cartilage and subchondral bone was blurred,and the matrix loss was serious.The Mankin's score was higher in the old group than the young group(P<0.05).The expression of matrix metalloproteinase 13,P53,P21 at Mrna and protein levels increased in the old group compared with the young group(P<0.05).Compared with the old group,electroacupuncture decreased the level of C-terminal peptide of type Ⅱ collagen(P<0.05),increased the bone volume fraction,bone mineral density and the number of bone trabeculae(P<0.05),and decreased the trabecular separation(P<0.05).Safranin O-fast green staining showed that in the electroacupuncture group,the surface of cartilage was smooth and red staining was uniform,and the cell morphology and structure were between the young group and the old group.Following electroacupuncture treatment,the Mankin's score(P<0.05),matrix metalloproteinase 13 and P21 Mrna expression(P<0.05),and matrix metalloproteinase 13 and P53 protein expression decreased(P<0.05),while there was a decreasing trend of P53 Mrna and P21 protein expression,but with no statistical significance(P>0.05).To conclude,electroacupuncture may delay articular cartilage degeneration and subchondral osteoporosis in aged rats by inhibiting the expression of P53 and P21,so as to protect joints and delay joint aging.
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BACKGROUND:The clinical application of Mongolian Medicine Erdun-uril in the treatment of osteoarthritis is effective,but its therapeutic effect and related mechanism are still unclear. OBJECTIVE:To observe the repairing process of osteoarthritis in rats by Mongolian Medicine Erdun-uril and analyze its mechanism. METHODS:Thirty male Sprague-Dawley rats(8 weeks of age)were selected to establsih an osteoarthritis model using intraarticular injection of sodium iodoacetate solution into the unilateral knee joint.Two weeks after modeling,the model rats were randomly divided into three groups:control group(n=6)was given normal saline by gavage,and low and high dose groups(n=12 per group)were given Erdun-uril 1.4 and 2 g,respectively,3 times per day.After 2 and 4 weeks of continuous administration,blood samples,articular cartilage and periarticular bone tissue were taken from rats to detect changes in cartilage metabolic markers(cartilage oligomeric matrix protein,proteoglycan),bone metabolic markers(bone alkaline phosphatase,keratan sulfate),inflammatory markers(interleukin 6,tumor necrosis factor α),lipid metabolic markers(total cholesterol,triacylglycerol).Histopathological changes were also observed. RESULTS AND CONCLUSION:qRT-PCR results showed that after 2 and 4 weeks of administration,the mRNA expression of cartilage oligomeric matrix protein,proteoglycan and bone alkaline phosphatase and keratan sulfate in knee cartilage of rats were significantly reduced in the low and high dose groups compared with the control group(P<0.05,P<0.01,P<0.001),with the reduction being more significant in the high dose group.After 2 and 4 weeks of administration,compared with the control group,serum tumor necrosis factor α and interleukin 6 levels were decreased(P<0.01,P<0.001)and total cholesterol and triacylglycerol levels were increased(P<0.05,P<0.01,P<0.001)in the low and high dose groups,with the improvement being more significant in the high dose group.Hematoxylin-eosin staining results showed that in the control group,there were large defective areas on the surface of the knee cartilage with unknown structure and severe inflammatory cell infiltration;in the low dose group,the surface of the knee cartilage was rough with disordered cell arrangement and the cartilage structure did not improve significantly after 2 weeks of administration,while the number of inflammatory cells in the knee cartilage was reduced and the cartilage structure was restored to some extent after 4 weeks of administration;in the high dose group,the structure of the knee cartilage become clear after 2 weeks of administration and even clearer after 4 weeks of administration,and the inflammation was significantly reduced after 2 weeks of administration.To conclude,Mongolian Medicine Erdun-uril with better anti-inflammatory properties can improve cartilage metabolism and obviously alleviate osteoarthritis in rats.
摘要
BACKGROUND:Anterior cruciate ligament injury tends to lead to secondary meniscus injury and osteoarthritis.At present,there are few studies on the mechanics of meniscus and articular cartilage injury caused by anterior cruciate ligament injury. OBJECTIVE:To study the effect of partial rupture of the anterior cruciate ligament on the stress of medial and lateral meniscus and articular cartilage of knee joint by finite element analysis. METHODS:The CT and MRI images of the knee joint of a healthy volunteer were selected,and the scan data were imported into Mimics,Geomagic and SolidWorks software.After registration and fusion,four kinds of three-dimensional knee joint models were established:models of intact anterior cruciate ligament,rupture of the posterior external tract of anterior cruciate ligament,rupture of the anterior internal tract of anterior cruciate ligament,and absence of anterior cruciate ligament.Finally,data were imported into Ansys software to apply four different modes of loads to the knee joint:Longitudinal loads of 750 N were applied to the top of the femur;longitudinal load of 750 N to the top of the femur and forward thrust of 134 N behind tibia;a longitudinal load of 750 N and a varus moment of 10 Nm were applied to the top of the femur to simulate genu varus;750 N longitudinal load and 4 Nm internal rotation moment were applied to the proximal end of the femur to simulate knee internal rotation.The finite element analysis of biomechanical stress changes of the meniscus and articular cartilage of the knee joint was carried out. RESULTS AND CONCLUSION:(1)In the straight position of the knee joint,when the anterior medial tract of the anterior cruciate ligament was broken and the anterior cruciate ligament was missing under longitudinal loads of 750 N at the top of the femur,the total stress and peak value of meniscus increased significantly,but the stress distribution of the meniscus and the stress of articular cartilage did not change significantly.In longitudinal load of 750 N to the top of the femur and forward thrust of 134 N behind tibia,the fracture of the anterior internal tract of the anterior cruciate ligament increased the tibia forward,the compressive stress of posterior angle of the meniscus increased,and the stress of the articular cartilage did not change significantly.During simulating genu varus,the posterior angular stress of the lateral meniscus decreased,the stress of the medial meniscus increased,and the stress of articular cartilage slightly decreased when anterior cruciate ligament injuries were complete.When the anterior internal tract of the anterior cruciate ligament was broken or absent under knee internal rotation,the equivalent stress peak value of femoral cartilage and tibia cartilage shifted from medial cartilage to lateral cartilage,and the stress peak value of meniscus increased significantly.At this time,the anterior internal tract of the anterior cruciate ligament played a leading role in the rotational stability of the knee joint.(2)These results indicate that the risk of secondary meniscus injury in patients with anterior and medial anterior cruciate ligament band rupture was much higher than that in patients with posterior and external anterior cruciate ligament band rupture when the knee was in the upright standing position,varus and pronation,and there was no significant difference in the impact on articular cartilage.
摘要
BACKGROUND:Cartilage degeneration and subchondral bone damage are the main pathological features of osteoarthritis,and treatment based on this pathological feature will be a promising improvement for osteoarthritis. OBJECTIVE:To design and study an annotated strontium ranelate-loaded drug delivery system and to observe its therapeutic effect on promoting cartilage repair and improving subchondral bone structure in osteoarthritis. METHODS:(1)In vitro experiment:Strontium ranelate was loaded into sodium alginate/collagen hydrogel matrix to construct in situ drug delivery system,and the in vitro slow release performance of the system was characterized.Strontium ranelate-loaded sodium alginate/collagen hydrogel(experimental group)and alginate sodium/collagen hydrogel(control group)were co-cultured with bone marrow mesenchymal stem cells,respectively,and cultured cells were used as a blank control group to detect cell proliferative activity.After chondroblast-induced differentiation,saffron O staining,Alcian blue staining and RT-qPCR were performed respectively.The two hydrogels were co-cultured with osteoblasts,and the cultured cells were used as a blank control group for immunofluorescence staining and RT-qPCR.(2)In vivo experiment:A total of 18 adult SD rats were selected and the model of right posterior knee osteoarthritis was established by the method of medial meniscectomy.After 1 week,the rats were divided into three groups by the random number table method:The blank group did not receive any treatment.The control group was injected with sodium alginate/collagen hydrogel in the knee,and the experimental group was injected with strontium ranelate-loaded sodium alginate/collagen hydrogel,with 6 rats in each group.After 6 weeks,the samples were subjected to Micro-CT scanning,hematoxylin-eosin staining,saffron O-solid green staining and immunofluorescence staining. RESULTS AND CONCLUSION:(1)In vitro experiment:Strontium ranelate-loaded sodium alginate/collagen hydrogel had porous microstructure and sustainable release of strontium ranelate.At 21 days,the cumulative release reached(60.89±0.58)%.Bone marrow mesenchymal stem cell staining showed that both hydrogels had good cytocompatibility.The results of the CCK-8 assay demonstrated that strontium ranelate-loaded sodium alginate/collagen hydrogel could promote the proliferation of bone marrow mesenchymal stem cells.The results of Safranin O staining,Alcian blue staining,immunofluorescence staining and RT-qPCR exhibited that strontium ranelate-loaded sodium alginate/collagen hydrogel could promote chondrogenic differentiation of bone marrow mesenchymal stem cells.Immunofluorescence staining and RT-qPCR revealed that strontium ranelate-loaded sodium alginate/collagen hydrogel could decrease bone resorptivity by increasing the ratio of osteophosphorin/nuclear factor κB receptor activator ligand.(2)In vivo experiment:Micro-CT scan verified that compared with the blank group and control group,the subchondral bone volume fraction and bone mineral density of the knee of rats were increased in the experimental group(P<0.05,P<0.01).Histological staining displayed that compared with the blank group and control group,the knee cartilage injury was significantly reduced;the expression of type II collagen was promoted,and the expression of matrix metalloproteinase 2 protein was inhibited in the experimental group(P<0.05,P<0.01).(3)These results confirm that the strontium ranelate-loaded sodium alginate/collagen hydrogel can promote the repair of cartilage defects in osteoarthritis and reconstruct the complex interface between cartilage and subchondral bone.
摘要
BACKGROUND:The repair of articular cartilage injury remains a difficult problem to be solved urgently in clinical practice.Utilizing synthetic or biological materials to promote cartilage regeneration has been a research hotspot. OBJECTIVE:To review the research progress of synthetic and biological materials in articular cartilage repair. METHODS:PubMed and CNKI databases were searched for articles about the progress of synthetic and biological materials utilized in articular cartilage repair."Collagen,gelatin,silk,chitosan,alginate,PEG,PCL,PLA,cartilage tissue engineering,cartilage tissue engineering materials"were used as English and Chinese search terms,respectively.After preliminary screening based on the inclusion and exclusion criteria,98 articles with high quality and relevance were retained for review. RESULTS AND CONCLUSION:Natural materials,including collagen,gelatin,silk,chitosan,and alginate,have good biocompatibility and degradability.Synthetic materials,containing polyethylene glycol,polycaprolactone,and polylactic acid,have good mechanical properties.Modification and composition of materials can overcome the inherent defects in materials and show better cartilage repair ability.Studies about multi-layer scaffolds based on hierarchical structure are rare,and it is more targeted at osteochondral injury repair rather than simple cartilage injury repair.At present,scaffold research is focused on the synthetic research and development stage,and the corresponding clinical trials are few,so it is necessary to pay attention to clinical transformation in the future.
摘要
BACKGROUND:Knee osteoarthritis is a common disease in middle-aged and elderly people.It is a kind of disease that seriously affects the quality of life of patients and even has the risk of disability.Therefore,the pathogenesis and treatment of knee osteoarthritis have become the focus of research.In Chinese medicine,knee osteoarthritis is often treated as"biness,"which is closely related to"biness"caused by blood stasis and blood vessels blocking collaterals in the theory of"blood stasis"in traditional Chinese medicine.Iron overload is a kind of pathological state caused by iron metabolism disorder,which highly coincides with the pathogenic characteristics and clinical manifestations of the"blood stasis"theory of traditional Chinese medicine,and is a risk factor that promotes the development of knee osteoarthritis. OBJECTIVE:Based on the"blood stasis"theory,to summarize the effects of iron overload on cartilage metabolism and subchondral bone reconstruction,to lay a new theoretical foundation for the treatment of knee osteoarthritis with traditional Chinese medicine,and to explore the therapeutic effect of traditional Chinese medicine for promoting blood circulation after interfering with bone tissue. METHODS:CNKI,WanFang database,PubMed and Web of Science databases were searched for relevant literature.The Chinese search terms were"ferroptosis,iron,iron overload,osteoarthritis,blood stasis"and the English search terms were"ferroptosis,iron,iron overload,osteoarthritis,TCM."In the end,76 articles were included for further review. RESULTS AND CONCLUSION:First of all,we explored the potential of the"blood stasis"theory in treating knee osteoarthritis,and found that"blood stasis"is a crucial part in the progress of knee osteoarthritis,indicating that the"blood stasis"theory is the key to the treatment of knee osteoarthritis in traditional Chinese medicine.Secondly,"blood stasis"and iron overload have a high degree of similarity in pathogenic factors,clinical manifestations,and pathogenic characteristics,suggesting the possibility of"blood stasis"theory in treating iron overload.This finding reminds us that iron overload may be an important mechanistic basis for the"blood stasis"theory in the treatment of knee osteoarthritis.The extracts of blood-activating drugs can relieve iron overload and treat knee osteoarthritis,but the specific mechanism is still unclear.Therefore,we believe that the relationship between"blood stasis"theory and iron overload and related mechanisms are important research directions for knee osteoarthritis in the future.The related mechanism of"blood stasis"theory to alleviate iron overload and then treat knee osteoarthritis also provides a theoretical basis for the modernization of traditional Chinese medicine,such as the development of new drugs and innovative usage,and has certain guiding significance for clinical practice.
摘要
BACKGROUND:Growth differentiation factor 5 is a member of the transforming growth factor superfamily and one of the earliest markers of joint development.Growth differentiation factor 5 has an important role in cartilage repair. OBJECTIVE:To explore the action mechanism of growth differentiation factor 5-induced chondrogenic differentiation of bone marrow mesenchymal stem cells. METHODS:Rabbit bone marrow mesenchymal stem cells were isolated and cultured.CCK-8 assay was used to detect the effect of different mass concentrations of growth differentiation factor 5 on the proliferation activity of bone marrow mesenchymal stem cells.RT-PCR was utilized to detect the expression of genes related to chondrogenic differentiation of bone marrow mesenchymal stem cells induced by different mass concentrations of growth differentiation factor 5.To further investigate the action mechanism of growth differentiation factor 5-induced chondrogenic differentiation of bone marrow mesenchymal stem cells,we added inhibitor XAV-939 and activator Laduviglusib of Wnt/β-catenin signaling pathways to induce cell culture for 14 days.RT-PCR and western blot assay were performed to detect the expression of cartilage-related genes and Wnt/β-catenin signaling pathway proteins. RESULTS AND CONCLUSION:(1)CCK-8 results showed no significant effect of growth differentiation factor 5 on the proliferation of bone marrow mesenchymal stem cells.(2)Growth differentiation factor 5 promoted the expression of cartilage-related genes type Ⅱ collagen,aggrecan and Sox9,among which growth differentiation factor 5 induced a significant upregulation of cartilage-related genes in the 50 ng/mL group.(3)Addition of Laduviglusib,an activator of Wnt/β-catenin signaling pathway,upregulated Sox9,β-catenin and type Ⅱ collagen expression(P<0.05).Addition of XAV939,an inhibitor of Wnt/β-catenin signaling pathway,down-regulated Sox9,β-catenin and type Ⅱ collagen expression(P<0.05).(4)Taken together,growth differentiation factor 5-induced chondrogenic differentiation of bone marrow mesenchymal stem cells may be associated with the activation of the Wnt/β-catenin signaling pathway.
摘要
BACKGROUND:Internal tension-reduction technique is to reconstruct the anterior cruciate ligament through high-strength suture system combined with tendon.It can effectively reduce graft relaxation and frets by sharing the internal load of the knee joint,and has achieved good biomechanical results and clinical efficacy.However,whether it can reduce cartilage degeneration after anterior cruciate ligament reconstruction through stress sharing reduction has not been studied. OBJECTIVE:To investigate the effect of internal tension-reduction technique on articular cartilage degeneration in southern Yunnan small-ear pigs undergoing anterior cruciate ligament reconstruction. METHODS:Ten adult female Yunnan small-ear pigs were selected,and the ipsilateral knee Achilles tendon was taken from the left knee joint for anterior cruciate ligament reconstruction(normal group,n=10),and the ipsilateral knee Achilles tendon from the right knee joint combined with internal tension-reduction and augmentation system for anterior cruciate ligament reconstruction(tension-reduction group,n=10).One year after surgery,the experimental pigs were sacrificed,and the left and right knee cartilage was taken for hematoxylin-eosin staining,Safranin O-fast green staining,Osteoarthritis Research Society International scoring,and immunohistochemistry staining of type Ⅱ collagen,interleukin-1β,and tumor necrosis factor-alpha in the cartilage. RESULTS AND CONCLUSION:Hematoxylin-eosin staining showed that in the tension-reduction group,there were mild pathologic changes of osteoarthritis,with a low number of empty bone lacunae and no obvious pathological changes such as fibrosis or cell layer breakage;in the normal group,more severe cartilage damage,with an increased number of empty bone lacunae,loss of chondrocytes near the bone and even the formation of fissures.Safranin O-fast green staining indicated that the tension-reduction group had normal cartilage tissue thickness,flat cartilage surface,a neat cell arrangement in a polar pattern,and no swelling or apoptosis,while in the normal group,the thickness of cartilage tissue was obviously thinner,the cell arrangement was disordered with no polarity,the number of cells was reduced,obvious cartilage fractures and cartilage vacuoles formed,and the absence of cells near the central bone was obvious.The Osteoarthritis Research Society International score was significantly lower in the tension-reduction group than in the normal group(P＜0.05).Immunohistochemical findings showed that the protein expression of type Ⅱ collagen in cartilage tissue of the tension-reducing group was higher than that of the normal group(P＜0.05),and the protein expression of interleukin 1β and tumor necrosis factor ɑ in cartilage tissue was lower than that of normal group(P＜0.05).To conclude,internal tension-reduction technique can delay the degeneration of articular cartilage in Yunnan small-eared pigs following anterior cruciate ligament reconstruction.