Injerto osteocondral congelado para tratamiento de lesiones de cartílago de rodilla: resultados a 7 años de seguimiento / Use of frozen osteochondral allograft for the treatment of cartilage defects of the knee. Results at seven-year follow-up

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.

Updates in the Treatment of Knee Osteoarthritis / Atualizações no tratamento da osteoartrite de joelho

Abstract Knee osteoarthritis (OA) is an inflammatory and degenerative condition resulting in articular cartilage destruction and functional loss. Its prevalence has grown considerably due to increased life expectancy and obesity, and its diagnosis relies on evaluation, medical examination, and confirmation by supplementary radiographic images. Knee OA is multifactorial and influenced by several local, systemic, and external aspects. In addition, its progress and therapeutic responses highly depend on the characteristics of each subject. The initial recommendation is drug treatment and alternative therapies to improve quality of life. However, if these treatments are unsuccessful, one must consider surgical treatment. Surgical options include arthroscopies, osteotomies, and partial and total arthroplasties, while non-surgical treatments include medications and alternative therapies such as infiltrations, acupuncture, and physical exercise. It is worth highlighting that biomarkers can be a significant strategy for early disease detection, assessment of disease activity, prediction of prognosis, and monitoring a better response to therapy. Nevertheless, this topic must be the focus of further research to confirm its findings.

Resumo A osteoartrite (OA) do joelho é uma doença inflamatória e degenerativa que ocasiona a destruição da cartilagem articular e leva à perda de funções. Sua prevalência vem crescendo consideravelmente devido ao aumento da expectativa de vida e da obesidade, e o diagnóstico pode ser feito por meio de avaliação e exames médicos, e é confirmado em imagens radiográficas complementares. Uma condição multifatorial, a OA do joelho pode ser influenciada por diversos aspectos locais, sistêmicos e externos; além disso, a sua evolução e as respostas aos tratamentos dependem muito das características de cada indivíduo. Inicialmente, recomenda-se proceder a um tratamento medicamentoso e a terapias alternativas que melhorem a qualidade de vida do paciente; mas, a partir do momento em que se verifica que tais terapias não estão proporcionando resultados satisfatórios, um tratamento cirúrgico deve ser considerado. Entre os tratamentos cirúrgicos, as artroscopias, as osteotomias e as artroplastias parciais e totais são destacadas; os métodos não cirúrgicos incluem o uso de medicamentos e de terapias alternativas, como infiltrações, acupuntura e prática de exercícios físicos. Vale ressaltar ainda que a utilização de biomarcadores pode ser uma importante estratégia para detectar precocemente a doença, avaliar sua atividade, prever um prognóstico e monitorar uma melhor resposta à terapia; porém, esse tema ainda deve ser foco de mais estudos para que os seus resultados sejam comprovados.

Ejercicio terapéutico en la disminución del dolor en pacientes con artrosis de rodilla grado 1: revisión sistemática / Therapeutic exercise to reduce pain in patients with grade 1 knee arthrosis: systematic review / Exercício terapêutico para reduzir a dor em pacientes com artrose grau 1 do joelho: revisão sistemática

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.

Effect of Danggui Niantongtang on Intestinal Flora of Knee Osteoarthritis Mice Based on 16S rDNA Sequencing / 中国实验方剂学杂志

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.

Three-dimensional finite element analysis of effects of partial anterior cruciate ligament rupture on knee joint stress / 中国组织工程研究

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.

Protective effect of anterior cruciate ligament reconstruction assisted by internal tension-reduction technique on the articular cartilage of southern Yunnan small-ear pigs / 中国组织工程研究

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.

Effects and problems of growth differentiation factor 5-induced multidirectional differentiation of mesenchymal stem cells / 中国组织工程研究

BACKGROUND:Growth differentiation factor 5,a member of the transforming growth factor-β superfamily and bone morphogenetic protein family,plays an important role in articular cartilage injury repair,bone regeneration,improvement of intervertebral disc degeneration,tendon healing,and neurodevelopment. OBJECTIVE:To review the research progress of growth differentiation factor 5 in inducing chondrocytes,nucleus pulposus-like cells,tendon cell differentiation,as well as inducing bone formation and neurodevelopment. METHODS:The search terms"growth differentiation factor 5,articular cartilage,bone,nucleus pulposus cells,tendon,nerve regeneration"were used in CNKI,WanFang and PubMed.According to the inclusion and exclusion criteria,the articles not related to the subject matter were excluded and 69 articles related to growth differentiation factor 5 were included. RESULTS AND CONCLUSION:(1)Growth differentiation factor 5 can induce chondrogenic and osteoblastic differentiation of mesenchymal stem cells,but the concentration boundary of growth differentiation factor 5 to induce chondrogenic or osteoblastic differentiation remains unclear.(2)Growth differentiation factor 5 can induce mesenchymal stem cells to differentiate into nucleus pulposus cells,which may play a role in the treatment of intervertebral disc degeneration.(3)Growth differentiation factor 5 can induce mesenchymal stem cells to differentiate into tendon cells and play an important role in tendon repair and prevention of postoperative tendon adhesion.(4)Growth differentiation factor 5 can induce neurodevelopment and promote nerve regeneration.

Yi medicine Sambucus adnata Wall methanol extract in a rat osteoarthritis model:therapeutic effect and target prediction / 中国组织工程研究

BACKGROUND:The Yi people have used Sambucus adnata Wall to treat fractures,bruises,arthritis,etc.The author's group found that the active site aqueous extract(SAW-A)and dichloromethane extract(SAW-B)can promote fracture healing by promoting the expression of genes related to osteoblast proliferation,differentiation and maturation,differentiation and maturation.However,the therapeutic effect of methanol extract(SAW-C)at its active site on osteoarthritis is unclear. OBJECTIVE:To investigate the therapeutic effect of Sambucus adnata Wall extract on osteoarthritis,and to identify the effective targets of Sambucus adnata Wall extract in the treatment of osteoarthritis by network pharmacology technology. METHODS:A rat osteoarthritis model was replicated by anterior cruciate ligamentectomy and model rats were then treated with methanol extract of Sambucus adnata Wall by gavage for 21 days.On the 21st day after modeling,the knee joint of rats was detected by X-ray,the width of the knee joint was measured,oxidative stress indexes and inflammatory factors levels in serum and joint lavage fluid were detected,the morphology of the knee joint was observed by hematoxylin-eosin staining,full-thickness cartilage and hyaline cartilage thickness were measured,and the content of articular cartilage proteoglycan was observed by safranin O-fast green staining.The"drug-component-disease-target"network was constructed.Gene ontology enrichment analysis and Kyoto encyclopedia of genes and genomes enrichment analysis of effective targets were performed,and protein-protein interaction network maps were constructed using cytoscape software. RESULTS AND CONCLUSION:Sambucus adnata Wall extract could reduce tumor necrosis factor-α level in joint lavage fluid and serum levels of prostaglandin E2 and malondialdehyde,while increase the level of superoxide dismutase;relieve joint swelling caused by osteoarthritis;improve the histopathological state of articular cartilage,maintain the thickness of full-thickness articular cartilage,hyaline cartilage and the area of bone trabeculae in subchondral bone;and effectively prevent the loss of proteoglycans in articular cartilage and have a chondroprotective effect.Network pharmacological results showed that the methanol extract of Sambucus adnata Wall may have some targets related to inhibition of tumor necrosis factor,AKT1,interleukin-6,MAPK3,and SRC as well as inhibition of over-activation of EGFR signaling pathway and AGE-RAGE signaling pathway.

Behavior of cartilage-derived microtissue and ability of cartilage formation in three-dimensional dynamic and static culture conditions / 中国组织工程研究

BACKGROUND:Compared with traditional two-dimensional culture,three-dimensional microtissue culture can show greater advantages.However,more favorable cultivation methods in three-dimensional culture still need to be further explored. OBJECTIVE:To evaluate the cell behavior of microtissue and its ability to promote cartilage formation under two three-dimensional culture methods. METHODS:Cartilage-derived microcarriers were prepared by chemical decellularization and tissue crushing.DNA quantification and nuclear staining were used to verify the success of decellularization,and histological staining was used to observe the matrix retention before and after decellularization.The microcarriers were characterized by scanning electron microscopy and CCK-8 assay.Cartilage-derived microtissues were constructed by combining cartilage-derived microcarriers with human adipose mesenchymal stem cells through three-dimensional static culture and three-dimensional dynamic culture methods.The cell viability and chondrogenic ability of the two groups of microtissues were detected by scanning electron microscopy,live and dead staining,and RT-qPCR. RESULTS AND CONCLUSION:(1)Cartilage-derived microcarriers were successfully prepared.Compared with before decellularization,the DNA content significantly decreased after decellularization(P<0.001).Scanning electron microscope observation showed that the surface of the microcarrier was surrounded by collagen,maintaining the characteristics of the natural extracellular matrix of cartilage cells.CCK-8 assay indicated that microcarriers had no cytotoxicity and could promote cell proliferation.(2)Scanning electron microscopy and live and dead staining results showed that compared with the three-dimensional static group,the three-dimensional dynamic group had a more extended morphology of microtissue cells,and extensive connections between cells and cells,between cells and matrix,and between matrix.(3)The results of RT-qPCR showed that the expressions of SOX9,proteoglycan,and type Ⅱ collagen in microtissues of both groups were increased at 7 or 14 days.The relative expression levels of each gene in the three-dimensional dynamic group were significantly higher than those in the three-dimensional static group at 14 days(P<0.05).At 21 days,the three-dimensional static group had significantly higher gene expression compared with the three-diomensional dynamic group(P<0.001).(4)The results showed that compared with three-dimensional static culture microtissue,three-dimensional dynamic culture microtissue could achieve higher expression of chondrogen-related genes in a shorter time,showing better cell viability and chondrogenic ability.

Research hotspots and trends in the field of articular cartilage repair:a visualization analysis / 中国组织工程研究

BACKGROUND:Due to the very limited ability of articular cartilage to repair itself,articular cartilage defects caused by natural degeneration or trauma often cannot be repaired on their own,which triggers or aggravates osteoarthritis and even leads to severe disability.Therefore,the repair treatment after articular cartilage injury has become an urgent clinical problem. OBJECTIVE:To summarize the hot research topics and development trends in the field of articular cartilage repair using bibliometric analysis. METHODS:Literature related to articular cartilage repair was searched from the Web of Science Core Collection from 2000 to 2023,and bibliometric and visualization analyses were carried out using VOSviewer,Citespeace and Bibliometrix R-package. RESULTS AND CONCLUSION:The annual publication volume in the field of articular cartilage repair shows an overall increasing trend,with the United States,China,and Germany being the top three countries in terms of publication volume,and the research institutions focus on universities and hospitals,with Harvard University,New York Hospital for Special Surgery,and Shanghai Jiao Tong University being the top three institutions in terms of publication volume.AMERICAN JOURNAL OF SPORTS MEDICINE is the journal that publishes the most research literature in the field,and BIOMATERIALS is the journal with the highest number of citations in the field."Injectable hydrogels for cartilage and bone tissue engineering"is the most cited document published in the last decade,and the author with the most publications is Madry Henning,an active author in the field.The active authors in this field have formed a number of stable research teams with each other,and the cooperation between different teams needs to be further strengthened.Intra-articular injections,high tibial osteotomies,hydrogels,drug delivery,inflammation,cartilage regeneration,and scaffolds are the current hot topics of research in this field,and the application of 3D printing technology,bio-inks,silk proteins,injectable hydrogels,and exosomes in articular cartilage repair may be the frontier of research in this field.Integrating various innovative technologies and methods for more effective,durable and functional cartilage tissue regeneration and repair,and facilitating the clinical translation of the relevant technologies and methods by conducting more high-quality clinical studies may be the future research trend in this field.

Pulsed electromagnetic fields inhibit knee cartilage degeneration in aged rats / 中国组织工程研究

BACKGROUND:Pulsed electromagnetic fields,as an important physical therapy,are exactly effective in the treatment of osteoarthritis,but the mechanism has not been fully clarified. OBJECTIVE:To observe the effect of pulsed electromagnetic field on the degeneration of knee joint cartilage in aged rats. METHODS:Eight 6-month-old Sprague-Dawley rats were selected as the young group and were subjected to normal diet with no treatment.Sixteen 22-month-old Sprague-Dawley rats were randomly divided into old group(n=8)and pulsed electromagnetic field group(n=8).The rats in the pulsed electromagnetic field group were subjected to a pulsed electromagnetic field intervention,once a day,5 days per week for continuous 8 weeks.The rats in the old group were given no treatment.All rats were anesthetized and executed after 8 weeks for the detection of relevant indexes. RESULTS AND CONCLUSION:Compared with the young group,serum type Ⅱ collagen C-terminal peptide level was increased in the old group(P<0.05);compared with the old group,serum type Ⅱ collagen C-terminal peptide level was decreased in the pulsed electromagnetic field group(P<0.05).Micro-CT showed that the bone volume fraction,bone mineral density,and number of bone trabeculae decreased(P<0.05)and the trabecular separation increased(P<0.05)in the tibia of rats in the aged group compared with the young group;and the bone volume fraction,bone density,and number of trabeculae increased(P<0.05)and the trabecular separation decreased(P<0.05)in the tibia of rats in the pulsed electromagnetic field group compared with the aged group.The tibial plateau Safranin O-fast green staining showed that the articular cartilage structure of rats in the aged group was disorganized,and the number of chondrocytes was obviously reduced,and the tidal line could not be distinguished.The above results were improved in the pulsed electromagnetic field group.RT-qPCR and western blot assay showed that the mRNA and protein expression levels of matrix metalloproteinase 1,matrix metalloproteinase 13,P53 and P21 in the articular cartilage and subchondral bone of rats were elevated in the aged group compared with the young group(P<0.05)and decreased in the pulsed electromagnetic field group compared with the old group(P<0.05).To conclude,pulsed electromagnetic fields may improve osteoarthritis in aged rats by inhibiting chondrocyte senescence,alleviating articular cartilage degradation and inhibiting subchondral bone osteoporosis through suppressing the expression of P53/P21.

Finite element analysis of effect of proximal fibular fracture on knee joint stress in an extended state / 中国组织工程研究

BACKGROUND:The traditional view is that proximal fibular fractures do not require fixation.Others and our research suggest that the proximal fibular structure plays an important role in the stability of the posterolateral structure of the knee joint,and its mechanism of action is worth studying. OBJECTIVE:To investigate the biomechanical effects of proximal fibular fractures on various structures of the knee joint in an extended state. METHODS:Finite element method was used to conduct simulated biomechanical experiments.A healthy young male volunteer was selected to establish a finite element model of the knee joint in an extended state using MRI and CT image data,and four proximal fibular shapes were simulated(Model A:intact,Model B:1 cm fracture below the fibular head,Model C:1 cm tip defect fracture from the proximal end of the fibula to the distal end,and Model D:2 cm bone defect from the proximal end of the fibula).A longitudinal concentrated load of 1 500 N was applied to the femoral shaft to compare and analyze the distribution and changing trend of the maximum equivalent stress and maximum first principal stress of each structure of the knee joint in an extended state under four working conditions. RESULTS AND CONCLUSION:(1)In Model A,the maximum equivalent stress in the tibial cartilage and lateral compartment of the meniscus was greater than that in the medial compartment,while the maximum first principal stress in the tibial plateau and medial compartment of the meniscus was greater than that in the lateral compartment.The maximum equivalent stress of the medial condyle of the femoral cartilage was greater than that of the lateral condyle,and the maximum first principal stress of the medial condyle of the femoral cartilage was greater than that of the medial condyle.(2)Compared to Model A,there was no significant difference in the magnitude and distribution of the maximum equivalent stress and maximum first principal stress in the cartilage and meniscus of Model C.(3)Compared to Model A,the maximum equivalent stress increase amplitude of Model B was in the order of medial tibial cartilage(14.9％),medial condyle of femoral cartilage(13.6％),and medial meniscus(6.6％).The maximum first principal stress increase amplitude was the medial meniscus(11.06％),the medial tibial cartilage(8.65％),and the medial condyle of the femoral cartilage(7.46％).The maximum equivalent stress increase amplitude of the ligament was as follows:popliteal arch ligament(33.2％)>anterior cruciate ligament(21.3％)>fibular collateral ligament(17％)>posterior cruciate ligament(14.3％)>anterior lateral collateral ligament(13.2％)>medial collateral ligament(10.1％).(4)Compared to Model A,the maximum equivalent stress increasing trend of Model D followed the medial tibial cartilage(19.5％),femoral cartilage medial condyle(17.9％),and medial meniscus(9.9％).The maximum first principal stress in sequence was the medial meniscus(14.04％),the medial tibial cartilage(13.03％),and the medial condyle of the femoral cartilage(11.37％).The increasing trend of maximum equivalent stress in ligaments was as follows:anterior cruciate ligament(25.2％)>posterior cruciate ligament(18.9％)>medial collateral ligament(18.5％)>anterior lateral collateral ligament(12.7％).(5)It is suggested that when the knee joint is extended,a 1 cm fracture below the fibular head and a 2 cm fibular tip bone defect have a significant impact on the structure of the medial ventricular cartilage,anterior cruciate ligament,and posterior lateral ligament complex.

Circular RNAs are involved in the pathogenesis of osteoarthritis through intracellular mechanisms / 中国组织工程研究

BACKGROUND:Currently,there is no drug that can completely cure osteoarthritis and its pathogenesis is still unclear.Circular RNAs(circRNAs)are differentially expressed in patients with osteoarthritis and are closely associated with various pathological processes in osteoarthritis.circRNAs play an important role in various physiological and pathological processes,such as chondrocyte homeostasis,extracellular matrix formation,and inflammatory response. OBJECTIVE:To mainly review the effects of circRNAs on pathological factors related to osteoarthritis,as well as the types and expression levels of circRNAs in osteoarthritis. METHODS:Related articles published from 1976 to August 2023 were retrieved from CNKI,WanFang,VIP,PubMed,Medline,Web of Science and Elsevier databases.The keywords were"osteoarthritis,circular RNA,non-coding RNA,synovial tissue,chondrocytes"in Chinese and English,respectively.All the relevant articles were screened,summarized,analyzed,and finally 69 papers were included in the review. RESULTS AND CONCLUSION:circRNAs are non-coding RNAs widely found in eukaryotic cells,with covalently closed continuous loop structure,but with no 5'hat structure and 3'poly A tail,which are involved in multi-gene and multi-target regulatory networks and cannot be degraded by nucleic acid exonucleases(RNase R).circRNAs have a high abundance,high conservativeness and stability,and cell and tissue specificity.circRNAs have biological functions such as acting as molecular sponges for miRNAs,regulating linear RNA transcription and RNA shearing,interacting with RNA-bound proteins,and translating proteins.circRNAs regulate chondrocyte apoptosis and proliferation,degradation of cartilage extracellular matrix,and inflammation and other physiopathologic processes.circRNAs are expected to become biomarkers and potential therapeutic targets for clinical diagnosis and prognosis of osteoarthritis,and may become a new strategy for clinical treatment of osteoarthritis in the future.

The Wave Sign Correlates with the Posterior Horn Medial Meniscus (PHMM) Tear in the Anterior Cruciate Ligament (ACL) Deficient Knee

@#Introduction: A posterior horn medial meniscus (PHMM) tear subjects the knee to pathological stresses, especially in the setting of a deficient anterior cruciate ligament (ACL). These PHMM tears have to be surgically addressed, however they remain a diagnostic challenge. Hence, this study aims to evaluate the wave sign as an arthroscopic diagnostic aid for the PHMM tear which may be occult. Materials and methods: This is a retrospective study of 61 consecutive patients (62 ACL-deficient knees) who underwent arthroscopic primary ACL reconstruction between September 2017 and August 2018. We defined PHMM tears as tears located in the posterior one-third of the medial meniscus. Root tears and ramp lesions were included in our analysis. The arthroscopic findings were recorded after a comprehensive arthroscopic survey. Results: In the sample of ACL-deficient knees, 44 (71.0%) had a concomitant medial meniscus tear. The most common location for the tear was in the posterior horn (81.8%). There were seven occult PHMM tears, not described by the radiologist or identified by the operating surgeon on the preoperative magnetic resonance imaging. The wave sign was identified in 10 (16.1%) knees, all confirming the presence of the PHMM tear. A positive correlation was found between the presence of the wave sign and the PHMM tear. Conclusions: The wave sign has a statistically significant but weak positive correlation with the presence of the PHMM. We view the wave sign as a valuable arthroscopic cue to rule-in the presence of the PHMM tear in the ACLdeficient knee.

Quantitative study of 3.0T MRI on the thickness of knee joint cartilage in healthy young people / 中国骨伤

OBJECTIVE@#To explore 3.0T MRI accurate measurement of knee cartilage thickness in healthy youth provides reliable anatomical parameters for quantitative diagnosis of osteoarthritis and accurate osteotomy of joint replacement.@*METHODS@#From January 2013 to December 2013, 30 healthy young volunteers including 14 males and 16 females with an average age of (25.8±2.4) years old ranging from 22 to 33 years were recruited in Changchun, Jilin Province, and a 3.0T MRI scan was performed on the bilateral knee joints of each volunteer. The cartilage thickness was measured on the lateral femoral condyle (LFC), medial femoral condyle (MFC), lateral tibial plateau (LTP) and medial tibial plateau (MTP).@*RESULTS@#In four regions of the knee joint:LFC, MFC, LTP and MTP, whether young men or women, there was no significant difference in cartilage thickness between the left and right knee joints (P>0.05). There were significant differences in knee cartilage thickness between healthy young men and women (P<0.05). In the same sex group, LFC cartilage thickness was thinner in the middle, thicker in front and rear;MFC cartilage thickness was the thinnest in front and gradually thickening from the front to the rear; LTP cartilage thickness was thickest in the middle, second in the rear and thinnest in the front;MTP cartilage thickness was the thinnest in the front, was relatively uniform in the middle and rear and thicker than that in the front.@*CONCLUSION@#In Northeast China, among healthy adults aged 22 to 33, gender difference may be an important factor in the difference of cartilage thickness in various regions of the knee joint. Regardless of whether male or female healthy young people, the cartilage thickness of the entire knee joint is unevenly distributed, but there is no significant difference in cartilage thickness in the same area between the left and right knee joints.

Research Progress on Biomechanics and Mechanobiology of Articular Cartilage in 2022 / 医用生物力学

As a kind of elastic load-bearing connective tissues on bone surface in dynamic joints, articular cartilage can provide low wear lubrication, shock absorption, load transfer and other supporting functions, and has hierarchical fiber composite structures and excellent mechanical properties. As an avascular and aneural tissue,the degenerated articular cartilage lacks the capability of self-healing after damage. The high incidence of arthritisis still a hot spot in basic and clinical researches. Articular cartilage is a mechanical sensitive tissue, andmechanical environment will affect the development of tissues in different directions. Extensive researches onbiomechanics and mechanobiology of articular cartilage were conducted in 2022. Many studies on morphology, function and mechanical state of cartilage,as well as mechanical state of cartilage under different conditions were reported. Some cartilage-related loading devices were designed at animal, tissue and cell levels. Researches onthe repair of cartilage degeneration and injury under mechanical loads were carried out in vitro and in vivo, andsome important repair method and means were obtained. The biomechanical and mechanobiology research on articular cartilage is the basis of arthritis, cartilage defect and repair. The influence of quantitative mechanical under 4 conditions on the repair of articular cartilage injury needs further study in vivo and in vitro

Mechanism of extracorporeal shock wave combined with platelet rich plasma in the treatment of articular cartilage injury in knee osteoarthritis rats based on the Sirt1/FoxO1 pathway / 国际生物医学工程杂志

Objective:To explore the mechanism of extracorporeal shock wave combined with platelet rich plasma in the treatment of articular cartilage injury in knee osteoarthritis (KOA) rats based on the silent information regulator 1 (Sirt1)/forkhead transcription factor O1 (FoxO1) pathway.Methods:15 SD rats were used for platelet rich plasma extraction and 35 SD rats were randomly divided into blank control group, model group, extracorporeal shock wave group, platelet rich plasma group, and extracorporeal shock wave + platelet rich plasma group. Each group had 7 cases. After the intervention, HE staining of articular cartilage tissue was used to observe changes in articular cartilage morphology, Mankin score was used for pathological evaluation, CCK-8 method was used to detect chondrocyte vitality and proliferation, ELISA method was used to detect inflammatory factor levels in joint fluid, and Western Blot method was used to detect the expression levels of Sirt1 and acely-FoxO1/FoxO1 in five groups of articular cartilage tissue.Results:The HE staining of articular cartilage tissue showed that model group, extracorporeal shock wave group, platelet rich plasma group, and extracorporeal shock wave + platelet rich plasma group had varying degrees of pathological damage, with model group having the most severe pathological damage, while the other three experimental groups had no significant differences. The Mankin score and the level of acely-FoxO1/FoxO1 in articular cartilage tissue showed that blank control group < extracorporeal shock wave + platelet rich plasma group < platelet rich plasma group < extracorporeal shock wave group < model group (all P < 0.05). The results of Sirt1 level in articular cartilage tissue, activity, and proliferation ability of articular chondrocytes showed that model group < extracorporeal shock wave group < platelet rich plasma group < extracorporeal shock wave + platelet rich plasma group < blank control group (all P < 0.05). Comparison of inflammatory factor levels in joint fluid, blank control group < extracorporeal shock wave + platelet rich plasma group < extracorporeal shock wave group < platelet rich plasma group < model group (all P < 0.05). Conclusions:The combination of extracorporeal shock wave and platelet rich plasma can promote the proliferation of osteoarthritis chondrocytes and alleviate joint inflammation and cartilage damage in KOA rats by upregulating Sirt1 expression and downregulating FoxO1 acetylation levels.

Repair Effects of Xiaoyusan New Formula on Cartilage Injury and MMP-13 Expression in Knee Osteoarthritis Model Rabbits / 实验动物与比较医学

ObjectiveTo study the effect of Xiaoyusan new formula on the articular cartilage of knee osteoarthritis (KOA) rabbits and its mechanism. MethodsA total of 42 New Zealand white rabbits aged 6 months were randomly divided into normal group, model group, ointment of Xiaoyusan group, and ointment of Xiaoyusan new formula group, with 10 rabbits in each group (the other 2 rabbits were used for model validation). Except for the normal group, the right knee joints of all rabbits in the other groups were prepared as KOA models according to the modified Hulth method. After 5 weeks of molding, the rabbits in ointment of Xiaoyusan group, ointment of Xiaoyusan New Formula group were given corresponding ointments for knee arthritis treatment, once a day, each time for 10 hours. After 2-week continuous administration and treatment, the knee joint cartilage of the four groups of rabbits was taken and the cartilage damage of each group was evaluated by Outerbridge grading method. The pathological changes of the cartilage, calcified layer and subchondral bone of the knee joint of rabbits in each group were observed by HE staining method under the light microscope, and the degree of cartilage degeneration was evaluated by Mankin's method. The expression of matrix metalloproteinase-13 (MMP-13) in the cartilage of rabbit knee joint in each group was deteced by immunohistochemistry. Results After the general observation of articular cartilage, the Outerbridge grading showed that the number of high-grade animals in ointment of Xiaoyusan group was reduced compared with the model group (P<0.05), and the number of high-grade animals in ointment of Xiaoyusan new formula group was also reduced (P<0.05) compared with ointment of Xiaoyusan group. HE staining showed that Mankin's scores of articular cartilage in the four groups ranked from high to low: model group (10.82±1.76), ointment of Xiaoyusan group (6.19±1.23), ointment of Xiaoyusan new formula group (2.64±1.18) and normal group (0.28±0.17). The difference among four groups was statistically significant (P<0.05). Immunohistochemical detection showed that the positive rates of MMP-13 expression in rabbit articular cartilage tissues in each group were (67.90±13.94)% of model group, (37.10±19.16)% of ointment of Xiaoyusan group, (13.60±3.10)% of ointment of Xiaoyusan new formula group and (3.20±2.39) % of normal group, ranking from high to low, and the difference among four groups was statistically significant (P<0.05). ConclusionXiaoyusan new formula can repair articular cartilage degeneration in KOA rabbits and decrease the expression of MMP-13 in cartilage, which may be one of the mechanisms of the treatment.

Advancing drug delivery to articular cartilage: From single to multiple strategies

Articular cartilage (AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis (OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intra-articular drug delivery systems (DDSs) in the future.

Inhibition of ADAMTS by iPSC⁃MSCs in vitro protects cartilage matrix in patients with osteoarthritis / 安徽医科大学学报

Objective @# To study the protective effect and mechanism of iPSC⁃MSCs on cartilage matrix in knee oste⁃ oarthritis (KOA) patients in vitro. @*Methods @#Cartilage tissues removed from KOA patients with joint replacement surgery were collected and subjected to tissue and cellular experiments , respectively. Cartilage tissue was cut into small pieces and randomly divided into a control group , an IL⁃1β ( 10 ng/ml) induction group , and iPSC⁃MSCs 96 h and then co⁃cultured with different amounts of iPSC⁃MSCs ( 1 × 104 , 1 × 105 , 1 × 106 ) cells for 72 h. For in tissues , the pathological changes of isolated cartilage tissues were examined by HE staining. The levels of ADAMTS⁃4 , ADAMTS⁃5 , and type II collagen expression were analyzed by immunohistochemistry , while the levels of MMP13 , IL⁃6 , and IL⁃10 in culture supernatants were detected by ELISA kits. The 2 to 5 generations of chondrocytes , which were extracted from cartilage tissue of KOA patients , were stimulated with IL⁃1β ( 10 ng/ml) for 48 h and then co⁃cultured with different concentrations of iPSC⁃MSCs ( 1 × 104 , 1 × 105 , 1 × 106 ) cells for 72 h. Immunofluorescence and Western blot detected the expression of RUNX2 , ADAMTS⁃4 , and ADAMTS⁃5 in chondrocytes. @*Results @#Comparison with the control group , in the IL⁃1β⁃induced group , the levels of RUNX2 , ADAMTS⁃4 , and ADAMTS⁃5 increased , the level of type II collagen decreased , the levels of MMP⁃13 and IL⁃6 in the culture supernatant increased ( P < 0. 05) , and the level of IL⁃10 decreased ( P < 0. 05) ; Compared with the IL⁃1β⁃induced decreased the expression of RUNX2 , ADAMTS⁃4 , and ADAMTS⁃5 , promoted type II collagen expression and elevated IL⁃10 levels. @*Conclusion @#iPSC⁃MSCs inhibited ADAMTS⁃4 and ADAMTS⁃5 expression in vitro , reduced cartilage extracellular matrix degradation , and played a role in articular cartilage protection.