Osteoarthritis is a common aging-related disorder that is confined mostly to the chondral layer of joints(e.g., the knee) but can spread to bony layers over time. In its early stages, osteoarthritis has minimal sympto...Osteoarthritis is a common aging-related disorder that is confined mostly to the chondral layer of joints(e.g., the knee) but can spread to bony layers over time. In its early stages, osteoarthritis has minimal symptoms;however, these gradually worsen over time and include joint pain, stiffness, loss of mobility, and inflammation. The exposed subchondral bone of a Grade 4 osteoarthritic knee is highly prone to erosion if left untreated due to persistent rubbing between the bones, which can lead to painful bone spurs. However, treating osteoarthritis is especially challenging due to the poor mitotic potential and low metabolic activity of chondrocytes. Although currently available tissue-engineered products(e.g., BST-CarGel■, TruFit■, and Atelocollagen■) can achieve structural reconstruction and tissue regeneration, final clinical outcomes can still be improved. Major challenges faced during clinical studies of tissue-engineered constructs include chondrocyte hypertrophy and the development of mechanically inferior fibrous tissue, among others. These issues can be addressed by selecting suitable biomaterial combinations, mimicking the three-dimensional(3D) architecture of the tissue matrix, and better controlling inflammation. Furthermore, it is crucial to generate essential signaling molecules within the articular cartilage ecosystem. This approach must also account for the microarchitecture of the affected joint and support the chondrogenic differentiation of mesenchymal stem cells. The use of tissue-engineered constructs has the potential to overcome each of these challenges, since materials can be modified for drug/biomolecule delivery while simultaneously facilitating the regeneration of robust articular cartilage. Three-dimensional printing has been successfully used in tissue engineering to achieve bioprinting. By manipulating conventional 3D printing techniques and the types of bioink used, many different types of bioprinting have emerged. Overall, these bioprinting techniques can be used to address various challenges associated with osteoarthritis treatment.展开更多
The primary objective of Cartilage Tissue Engineering(CTE)involves repairing or rebuilding impaired cartilage in an effort to restore joint functionality and enhance patients'quality of life.In this field,research...The primary objective of Cartilage Tissue Engineering(CTE)involves repairing or rebuilding impaired cartilage in an effort to restore joint functionality and enhance patients'quality of life.In this field,researchers are constantly exploring new materials and technologies to address the challenges posed by cartilage damage.Biomimetic hydrogels present several distinct advantages in articular cartilage repair when compared to conventional treatment methods like minimally invasive surgery,joint replacement,and drug therapies.These hydrogels effectively mimic the mechanical characteristics of natural cartilage while also promoting cell adhesion,proliferation,and differentiation through the inclusion of bioactive factors.This results in the creation of high-performance biomaterials,positioning them as a particularly promising therapeutic option.Recently,researchers have drawn inspiration from the intricate structures found in soft tissues to develop various types of biomimetic hydrogels.These innovative hydrogels find applications across various fields,such as biomedicine,tissue engineering,and flexible electronics.In tissue engineering,these materials serve as optimal scaffolds for cartilage regeneration and aid in restoring tissue function.Nevertheless,creating and manufacturing biomimetic hydrogels with complex designs,strong mechanical properties,and multifunctionality poses significant challenges.This paper reviews existing studies on natural and synthetic matrices for biomimetic hydrogels,explores the similarities between these hydrogels and natural cartilage,examines their biological and physical characteristics,discusses their advantages and limitations,and suggests future research avenues.展开更多
OBJECTIVE: To corroborate the efficacy of Jintiange capsules(JTGs)( 金天格胶囊) in the treatment of osteoarthritis(OA) by exploring the potential mechanism of action of synovial mesenchymal stem cell exosomes(SMSC-Exo...OBJECTIVE: To corroborate the efficacy of Jintiange capsules(JTGs)( 金天格胶囊) in the treatment of osteoarthritis(OA) by exploring the potential mechanism of action of synovial mesenchymal stem cell exosomes(SMSC-Exos) and articular chondrocytes(ACs) through transcriptome sequencing(RNA-seq). METHODS: Type Ⅱ collagenase was used to induce OA in rats. The efficacy of JTGs was confirmed by macroscopic observation of articular cartilage, micro-CT observation, and safranin fast green staining. After SMSC-Exos and ACs were qualified, RNA-seq was used to screen differentially expressed mi RNAs and m RNAs. The target genes of differentially expressed mi RNAs in Synovial mesenchymal stem cells(SMSCs) were predicted based on the multi Mi R R package. The codifferentially expressed genes of SMSC-Exos and ACs were obtained by venny 2.1.0. The mi RNA-m RNA regulatory network was constructed by Cytoscape software. Based on the Omic Share platform, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed on the m RNA regulated by key mi RNAs. Expression trend analysis was performed for co-differentially expressed genes. Correlation analysis was performed on micro-CT efficacy indicators, co-differentially expressed genes mRNA and miRNA. RESULTS: The efficacy of each administration group of JTGs was significant compared with the model group. SMSC-Exos and ACs were identified by their characteristics. The expression of rno-mi R-23a-3p, rnomi R-342-3p, rno-miR-146b-5p, rno-miR-501-3p, rnomiR-214-3p was down-regulated in OA pathological state, and the expression of rno-mi R-222-3p, rno-mi R-30e-3p, rno-mi R-676, and rno-miR-192-5p expression was upregulated, and the expression of all these mi RNAs was reversed after the intervention with JTGs containing serum. The co-differentially expressed genes were enriched in the interleukin 17 signaling pathway, tumor necrosis factor signaling pathway, transforming growth factor-β signaling pathway, etc. The expression trends of Ccl7, Akap12, Grem2, Egln3, Arhgdib, Ccl20, Mmp12, Pla2g2a, and Nr4a1 were significant. There was a correlation between micro-CT pharmacodynamic index, m RNA, and mi RNA. CONCLUSION: JTGs can improve the degeneration of joint cartilage and achieve the purpose of cartilage protection, which can be used for the treatment of OA. SMSCs-related mi RNA expression profiles were significantly altered after the intervention with JTGs containing serum. The 9 co-differentially expressed genes may be the key targets for the efficacy of JTGs in the treatment of OA rats, which can be used for subsequent validation.展开更多
Cartilage regeneration and repair are considered clinical challenges since cartilage has limited capability for reconstruction.Although tissue-engineered materials have the ability to repair cartilage,they have weak m...Cartilage regeneration and repair are considered clinical challenges since cartilage has limited capability for reconstruction.Although tissue-engineered materials have the ability to repair cartilage,they have weak mechanical characteristics and cannot resist long-term overload.On the other hand,surgery to replace the joint is frequently done to treat significant cartilage deterioration these days.However,the materials that are being used for replacement have high friction coefficients,lack shock absorption functions,and lack cushioning.Further research on natural articular cartilage structure and function may lead to bionic hydrogels,which have suitable physicochemical and biological characteristics(e.g.,tribological and mechanical properties and the ability to support loadbearing capability),but need improvements.Based on their tribological and mechanical characteristics,the current review highlights the most recent advancements of bionic hydrogels used for articular cartilage,highlighting both the field's recent progress and its potential for future research.For this reason,firstly,some important property improvement methods of bionic hydrogels are discussed and then,the recent findings of various research on the making of those bionic materials are provided and compared.It seems that by using some modifications such as product design,surface treatments,animal tests,controlling the isoelectric point of hydrogels,and computer simulation,the intended mechanical and tribological characteristics of natural articular cartilage may be attained by the bionic hydrogels.展开更多
PRIMARY synovial chondromatosis is a rarecondition in which foci of cartilage develop in thesynovial membrane of joints, bursae and tendonsheaths. It typically involves a single large jointin a young adult male.1 The ...PRIMARY synovial chondromatosis is a rarecondition in which foci of cartilage develop in thesynovial membrane of joints, bursae and tendonsheaths. It typically involves a single large jointin a young adult male.1 The ectopic foci of cartilage canresult in painful joint effusion, and the generation of loosebodies can cause mechanical symptoms.2,3 The etiology ofprimary synovial chondromatosis remains unknown, butmetaplastic theory is the most popular hypothesis. Thecommonly involved joints are knee, elbow, and hip.^4 Theshoulder is a rare site of synovial chondromatosis2,3,5 andthe extra-articular involvement even rarer, with only fewcases presented in literature. This report presents a rarecase of primary combined intra-articular andextra-articular synovial chondromatosis of shoulder jointtreated with arthroscopy.展开更多
It has been previously reported that small mother against decapentaplegic 3 （Smad3） gene knockout （Smad3^ex8/ex8） mice displays phenotypes similar to human osteoarthritis, as characterized by abnormal hypertrophic...It has been previously reported that small mother against decapentaplegic 3 （Smad3） gene knockout （Smad3^ex8/ex8） mice displays phenotypes similar to human osteoarthritis, as characterized by abnormal hypertrophic differentiation of articular chondrocytes. To further clarify the crucial target genes that mediate transformation growth factor-β （TGF-β）/Smad3 signals on articular chondrocytes differentiation and investigate the underlying molecular mechanism of osteoarthritis, microarrays were used to perform comparative transcriptional profiling in the articular cartilage between Smad3^ex8/ex8and wild-type mice on day five after birth. The gene profding results showed that the activity of bone morphogenetic protein （BMP） and TGF-β/cell division cycle 42 （Cdc42） signaling pathways were enhanced in Smad3^ex8/ex8 chondrocytes. Moreover, there was altered gene expression in growth hormone/insulin-like growth factor 1 （Igfl） axis and fibroblast growth factor （Fgf） signaling pathway. Notably, protein synthesis related genes and electron transport chain related genes were upregulated in Smad3^ex8/ex8 chondrocytes, implying that accelerated protein synthesis and enhanced cellular respiration might contribute to hypertrophic differentiation of articular chondrocytes and the pathogenesis of osteoarthritis.展开更多
<strong>Introduction:</strong> Purpose to study prevalence of the intraarticular chondral lesion in the malleolar fracture by using ankle arthroscopy to fully understand the severity and complexity of the ...<strong>Introduction:</strong> Purpose to study prevalence of the intraarticular chondral lesion in the malleolar fracture by using ankle arthroscopy to fully understand the severity and complexity of the injury. <strong>Methods:</strong> Cross sectional study of 32 patients diagnosed with ankle fracture and undergone open reduction and internal fixation with arthroscopic assessment performed stimultaneously. The mechanism of injury, patterns of injury and intraarticular chondral injury were documented. <strong>Results:</strong> Mean age was 38 years (SD = 14.1, range 18 - 68 years). Eighteen were female and 14 were male. Fifteen involved syndesmostic distruption, 22 had Danis-Weber B injury and 16 had supination external rotation (SER). Ten (31.2%) had positive intraoperative cartilage injury. Significant correlation between the Lauge-Hansen classifications with positive findings with 6 had SER, 2 had pronation adduction and 2 had pronation external rotation.<strong> Conclusion: </strong>The prevalence of chondral injury in ankle fracture was quite high and may leads to poor outcome. Arthroscopy procedure allow surgeon to assess intraarticular surface and reduction of the ankle fracture which prompt further intervention that may improve the clinical outcomes and prognosis of the patients.展开更多
Since articular cartilage possesses only a weak capac-ity for repair, its regeneration potential is considered one of the most important challenges for orthopedic surgeons. The treatment options, such as marrow stimul...Since articular cartilage possesses only a weak capac-ity for repair, its regeneration potential is considered one of the most important challenges for orthopedic surgeons. The treatment options, such as marrow stimulation techniques, fail to induce a repair tissue with the same functional and mechanical properties of native hyaline cartilage. Osteochondral transplantation is considered an effective treatment option but is as-sociated with some disadvantages, including donor-site morbidity, tissue supply limitation, unsuitable mechani-cal properties and thickness of the obtained tissue. Although autologous chondrocyte implantation results in reasonable repair, it requires a two-step surgical pro-cedure. Moreover, chondrocytes expanded in culture gradually undergo dedifferentiation, so lose morpho-logical features and specialized functions. In the search for alternative cells, scientists have found mesenchymal stem cells(MSCs) to be an appropriate cellular mate-rial for articular cartilage repair. These cells were origi-nally isolated from bone marrow samples and further investigations have revealed the presence of the cells in many other tissues. Furthermore, chondrogenic dif-ferentiation is an inherent property of MSCs noticedat the time of the cell discovery. MSCs are known to exhibit homing potential to the damaged site at which they differentiate into the tissue cells or secrete a wide spectrum of bioactive factors with regenerative proper-ties. Moreover, these cells possess a considerable im-munomodulatory potential that make them the general donor for therapeutic applications. All of these topics will be discussed in this review.展开更多
AIM To determine peculiarities of tissue responses to manual and automated Ilizarov bone distraction in nerves and articular cartilage.METHODS Twenty-nine dogs were divided in two experimental groups: Group M-leg leng...AIM To determine peculiarities of tissue responses to manual and automated Ilizarov bone distraction in nerves and articular cartilage.METHODS Twenty-nine dogs were divided in two experimental groups: Group M-leg lengthening with manual distraction(1 mm/d in 4 steps), Group A-automated distraction(1 mm/d in 60 steps) and intact group. Animals were euthanized at the end of distraction, at 30 th day of fixation in apparatus and 30 d after the fixator removal. M-responses in gastrocnemius and tibialis anterior muscles were recorded, numerical histology of peronealand tibialis nerves and knee cartilage semi-thin sections, scanning electron microscopy and X-ray electron probe microanalysis were performed.RESULTS Better restoration of M-response amplitudes in leg muscles was noted in A-group. Fibrosis of epineurium with adipocytes loss in peroneal nerve, subperineurial edema and fibrosis of endoneurium in some fascicles of both nerves were noted only in M-group, shares of nerve fibers with atrophic and degenerative changes were bigger in M-group than in A-group. At the end of experiment morphometric parameters of nerve fibers in peroneal nerve were comparable with intact nerve only in A-group. Quantitative parameters of articular cartilage(thickness, volumetric densities of chondrocytes, percentages of isogenic clusters and empty cellular lacunas, contents of sulfur and calcium) were badly changed in M-group and less changed in A-group.CONCLUSION Automated Ilizarov distraction is more safe method of orthopedic leg lengthening than manual distraction in points of nervous fibers survival and articular cartilage arthrotic changes.展开更多
Osteoarthritis is the most prevalent chronic and debilitating joint disease,resulting in huge medical and socioeconomic burdens.Intra-articular administration of agents is clinically used for pain management.However,t...Osteoarthritis is the most prevalent chronic and debilitating joint disease,resulting in huge medical and socioeconomic burdens.Intra-articular administration of agents is clinically used for pain management.However,the effectiveness is inapparent caused by the rapid clearance of agents.To overcome this issue,nanoparticles as delivery systems hold considerable promise for local control of the pharmacokinetics of therapeutic agents.Given the therapeutic programs are inseparable from pathological progress of osteoarthritis,an ideal delivery system should allow the release of therapeutic agents upon specific features of disorders.In this review,we firstly introduce the pathological features of osteoarthritis and the design concept for accurate localization within cartilage for sustained drug release.Then,we review the interactions of nanoparticles with cartilage microenvironment and the rational design.Furthermore,we highlight advances in the therapeutic schemes according to the pathology signals.Finally,armed with an updated understanding of the pathological mechanisms,we place an emphasis on the development of“smart”bioresponsive and multiple modality nanoparticles on the near horizon to interact with the pathological signals.We anticipate that the exploration of nanoparticles by balancing the efficacy,safety,and complexity will lay down a solid foundation tangible for clinical translation.展开更多
It is well known that subtle changes in structure and tissue composition of articular cartilage can lead to its degeneration. The present paper puts forward a modified layered inhomogeneous triphasic model with four p...It is well known that subtle changes in structure and tissue composition of articular cartilage can lead to its degeneration. The present paper puts forward a modified layered inhomogeneous triphasic model with four parameters based on the inhomogeneous triphasic model proposed by Narmoneva et al. Incorporating a piecewise fitting optimization criterion, the new model was used to obtain the uniaxial modulus Ha, and predict swelling pattern for the articular cartilage based on ultrasound-measured swelling strain data. The results show that the new method can be used to provide more accurate estimation on the uniaxial modulus than the inhomogeneous triphasic model with three parameters and the homogeneous mode, and predict effectively the swell- ing strains of highly nonuniform distribution of degenerated articular cartilages. This study can provide supplementary information for exploring mechanical and material properties of the cartilage, and thus be helpful for the diagnosis of osteoarthritis-related diseases.展开更多
Objective： In our previous work, we prepared a type of chitosan hydrogel with excellent biocompatibility. In this study, tissue-engineered cartilage constructed with this chitosan hydrogel and costal chondrocytes was...Objective： In our previous work, we prepared a type of chitosan hydrogel with excellent biocompatibility. In this study, tissue-engineered cartilage constructed with this chitosan hydrogel and costal chondrocytes was used to repair the articular cartilage defects. Methods： Chitosan hydrogels were prepared with a crosslinker formed by combining 1,6-diisocyanatohexane and polyethylene glycol. Chitosan hydrogel scaffold was seeded with rabbit chondrocytes that had been cultured for one week in vitro to form the preliminary tissue-engineered cartilage. This preliminary tissue-engineered cartilage was then transplanted into the defective rabbit articular cartilage. There were three treatment groups： the experimental group received preliminary tissue-engineered cartilage; the blank group received pure chitosan hydrogels; and, the control group had received no implantation. The knee joints were harvested at predetermined time. The repaired cartilage was analyzed through gross morphology, histologically and immunohistochemically. The repairs were scored according to the international cartilage repair society （ICRS） standard. Results： The gross morphology results suggested that the defects were repaired completely in the experimental group after twelve weeks. The regenerated tissue connected closely with subchondral bone and the boundary with normal tissue was fuzzy. The cartilage lacuna in the regenerated tissue was similar to normal cartilage lacuna. The results of ICRS gross and histological grading showed that there were significant differences among the three groups （P〈0.05）. Conclusions： Chondrocytes implanted in the scaffold can adhere, proliferate, and secrete extracellular matrix. The novel tissue-engineered cartilage constructed in our research can completely repair the structure of damaged articular cartilage.展开更多
Objective Using MR T2-mapping and histopathologic score for articular cartilage to evaluate the effect of structural changes in subchondral bone on articular cartilage. Methods Twenty-four male Beagle dogs were random...Objective Using MR T2-mapping and histopathologic score for articular cartilage to evaluate the effect of structural changes in subchondral bone on articular cartilage. Methods Twenty-four male Beagle dogs were randomly divided into a subchondral bone defect group （n = 12） and a bone cement group （n = 12）. Models of subchondral bone defectin the medial tibial plateau and subchondral bone filled with bone cement were constructed. In all dogs, the left knee joint was used as the experimental sideand the right knee as the sham side. The T2 value for articular cartilage at the medial tibial plateau was measured at postoperative weeks 4, 8, 16, and 24. The articular cartilage specimens were stained with hematoxylin and eosin, and evaluated using the Mankin score. Results There was a statistically significant difference （P 〈 0.05） in Mankin score between the bone defect group and the cement group at postoperative weeks 16 and 24. There was a statistically significant difference in the T2 values between the bone defect group and its sham group （P 〈 0.05） from week 8, and between the cement group and its sham group （P 〈 0.05） from week 16. There was significant difference in T2 values between the two experimental groups at postoperative week 24 （P 〈 0.01）. The T2 value for articular cartilage was positively correlated with the Mankin score （ρ = 0.758, P 〈 0.01）. Conclusion Structural changes in subchondral bone can lead to degeneration of the adjacent articular cartilage. Defects in subchondral bone cause more severe degeneration of cartilage than subchondral bone filled with cement. The T2 value for articular cartilage increases with the extent of degeneration. MR T2-mapping images and the T2 value for articular cartilage can indicate earlycartilage degeneration.展开更多
Osteochondral allografting has been proved to be a useful method to treat diseased or damaged areas of joint surfaces. Operational long-term stocks of grafts which supply a buffer between procurement and utilization w...Osteochondral allografting has been proved to be a useful method to treat diseased or damaged areas of joint surfaces. Operational long-term stocks of grafts which supply a buffer between procurement and utilization would contribute to the commercialization or industrialization of this technology. Vitrification has been thought to be a promising method for successful preservation of articular cartilage （AC）, but high concentration cryoprotectants （CPAs） are used which may cause high cellular toxicity. An effective way to reduce CPA toxioity is to increase CPA concen- tration gradually while the temperature is lowered. Understanding the mechanism of （31~A permeation at subzero temperatures is important for designing the cryopreservation protocol. In this research, the permeation of dimethyl sulfoxide （MezSO） in ovine AC at subzero temperatures was studied experimentally. Pretreated AC discs were ex- posed in Me2SO solutions for different time （0, 5, 15, 30, 50, 80, and 120 min） at three temperature levels （-10, -20, and -30℃）. The Me2SO concentration within the tissue was determined by ultraviolet （UV） spectrophotometry. The diffusion coefficients were estimated to be 0.85×10-6, 0.48×10-8, and 0.27×10-6 cm2/s at -10, -20, and -,30℃, respectively, and the corresponding activation energy was 29.23 kJ/mol. Numerical simulation was performed to com- pare two Me2SO addition protocols, and the results demonstrated that the total loading duration could be effectively reduced with the knowledge of permeation kinetics.展开更多
Articular cartilage(AC)is an avascular and flexible connective tissue located on the bone surface in the diarthrodial joints.AC defects are common in the knees of young and physically active individuals.Because of the...Articular cartilage(AC)is an avascular and flexible connective tissue located on the bone surface in the diarthrodial joints.AC defects are common in the knees of young and physically active individuals.Because of the lack of suitable tissue-engineered artificial matrices,current therapies for AC defects,espe-cially full-thickness AC defects and osteochondral interfaces,fail to replace or regenerate damaged carti-lage adequately.With rapid research and development advancements in AC tissue engineering(ACTE),functionalized hydrogels have emerged as promising cartilage matrix substitutes because of their favor-able biomechanical properties,water content,swelling ability,cytocompatibility,biodegradability,and lubricating behaviors.They can be rationally designed and conveniently tuned to simulate the extracel-lular matrix of cartilage.This article briefly introduces the composition,structure,and function of AC and its defects,followed by a comprehensive review of the exquisite(bio)design and(bio)fabrication of func-tionalized hydrogels for AC repair.Finally,we summarize the challenges encountered in functionalized hydrogel-based strategies for ACTE both in vivo and in vitro and the future directions for clinical translation.展开更多
For improving the theory of gradient microstructure of cartilage/bone interface, human distal femurs were studied. Scanning Electron Microscope （SEM）, histological sections and MicroCT were used to observe, measure ...For improving the theory of gradient microstructure of cartilage/bone interface, human distal femurs were studied. Scanning Electron Microscope （SEM）, histological sections and MicroCT were used to observe, measure and model the micro- structure of cartilage/bone interface. The results showed that the cartilage/bone interface is in a hierarchical structure which is composed of four different tissue layers. The interlocking of hyaline cartilage and calcified cartilage and that of calcified car- tilage and subchondral bone are in the manner of＂protrusion-pore＂ with average diameter of 17.0 gm and 34.1 lam respectively. In addition, the cancellous bone under the cartilage is also formed by four layer hierarchical structure, and the adjacent layers are connected by bone trabecula in the shape of H, I and Y, forming a complex interwoven network structure. Finally, the simplified structure model of the cartilage/bone interface was proposed according to the natural articular cartilage/bone interface. The simplified model is a 4-layer gradient biomimetic structure, which corresponds to four different tissues of natural cartilage/bone interface. The results of this work would be beneficial to the design of bionic scaffold for the tissue engineering of articular cartilage/bone.展开更多
BACKGROUND Inflammatory cytokines play a vital role in the occurrence of osteoarticular injury and inflammation. Whether inflammation-associated factors interleukin-1β(IL- 1β), IL-6, tumor necrosis factor-α(TNF-α)...BACKGROUND Inflammatory cytokines play a vital role in the occurrence of osteoarticular injury and inflammation. Whether inflammation-associated factors interleukin-1β(IL- 1β), IL-6, tumor necrosis factor-α(TNF-α) and vascular endothelial growth factor (VEGF) are involved in the pathogenesis of keen articular cartilage injury remains poorly understood. AIM To measure the levels of inflammatory factors [IL-1β, IL-6, TNF-α and VEGF] in patients with knee articular cartilage injury. METHODS Fifty-five patients with knee articular cartilage injury were selected as patient groups, who were divided into three grades [mild (n = 20), moderate (n = 19) and severe (n = 16)] according to disease severity and X-ray examinations. Meanwhile, 30 healthy individuals who underwent physical examination were selected as the control group. The levels of IL-1β, IL-6, TNF-α and VEGF were measured by ELISA and immunohistochemical staining. RESULTS Compared with the control group, patient groups displayed significantly higher levels of IL-1β, IL-6, TNF-α and VEGF, and the extent of increase was directly proportional to the severity of injury (P < 0.05). In addition, the number of cells with positive staining of IL-1β, IL-6, TNF-α and VEGF in the synovial membrane were significantly increased, along with increased disease severity (P < 0.05). After treatment, the scores of visual analogue scale and the Western Ontario and McMaster University of Orthopaedic Index in patient groups were 2.26 ± 1.13 and 15.56 ± 7.12 points, respectively, which were significantly lower than those before treatment (6.98 ± 1.32 and 49.48 ± 8.96). Correlation analysis suggested that IL-1β and TNF-α were positively correlated with VEGF. CONCLUSION IL-1β, IL-6, TNF-α and VEGF levels are increased in patients with knee articular cartilage injury, and are associated with the disease severity, indicating they might play an important role in the occurrence and development of knee articular cartilage injury. Furthermore, therapeutically targeting them might be a novel approach for the treatment of keen articular cartilage injury.展开更多
The microgravity environment of a long-term space flight may induce acute changes in an astronaut＇s musculo-skeletal systems. This study explores the effects of simulated microgravity on the mechanical characteristic...The microgravity environment of a long-term space flight may induce acute changes in an astronaut＇s musculo-skeletal systems. This study explores the effects of simulated microgravity on the mechanical characteristics of articular cartilage. Six rats underwent tail suspension for 14 days and six additional rats were kept under normal earth gravity as controls. Swelling strains were measured using high-frequency ultrasound in all cartilage samples subject to osmotic loading. Site-specific swelling strain data were used in a triphasic theoretical model of cartilage swelling to determine the uniaxial modulus of the cartilage solid matrix. No severe surface irregularities were found in the cartilage samples obtained from the control or tail-suspended groups. For the tail-suspended group, the thickness of the cartilage at a specified site, as determined by ultrasound echo, showed a minor decrease. The uniaxial modulus of articular cartilage at the specified site decreased significantly, from （6.31 ± 3.37） MPa to （5.05 ± 2.98）MPa （p 〈 0.05）. The histology- stained image of a cartilage sample also showed a reduced number of chondrocytes and decreased degree of matrix staining. These results demonstrated that the 14 d simulated microgravity induced significant effects on the mechanical characteristics of articular cartilage. This study is the first attempt to explore the effects of simulated microgravity on the mechanical characteristics of articular cartilage using an osmotic loading method and a triphasic model. The conclusions may provide reference information for manned space flights and a better understanding of the effects of microgravity on the skeletal system.展开更多
BACKGROUND Non-steroid anti-inflammatory drugs(NSAIDs)have played a crucial role in the treatment of osteoarthritis,especially in the early stages.However,the cardiovascular risk and adverse gastrointestinal reactions...BACKGROUND Non-steroid anti-inflammatory drugs(NSAIDs)have played a crucial role in the treatment of osteoarthritis,especially in the early stages.However,the cardiovascular risk and adverse gastrointestinal reactions of oral NSAIDs in elderly people cannot be underestimated.Intra-articular injection of NSAIDs may be a new attempt for early knee osteoarthritis treatment.Parecoxib may be a suitable drug for intra-articular injection.AIM To observe the clinical efficacy of the intra-articular injection of parecoxib for early knee osteoarthritis.METHODS Early knee osteoarthritis patients(n=110)were retrospectively analyzed.These patients were divided into three groups:Basic treatment+oral glucosamine(group A,n=37),oral celecoxib+basic treatment+oral glucosamine(group B,n=37),and intra-articular injection of parecoxib+basic treatment+oral glucosamine(group C,n=36).Intra-articular injection of parecoxib was performed once every 2 wk at a dose of 40 mg each time,for three times total.The three groups were compared in terms of visual analogue scale(VAS)scores,Hospital for Special Surgery(HSS)scores and patient satisfaction before and after treatment.The levels of inflammatory cytokines in the synovial fluid were detected in the three groups before and after treatment.RESULTS All patients were followed up for an average of 15.5±2.7 mo.The clinical efficacy was estimated by VAS and HSS scores at 12 mo after treatment.Inflammatory cytokine levels in the synovial fluid were evaluated at 3 mo after treatment.VAS and HSS scores were significantly improved in each group compared with before(P<0.001).There were significant differences among the three groups in VAS and HSS scores(P<0.001).The clinical efficacy of group C was superior to that of groups A and B(P<0.001),while group B outperformed group A in this respect(P<0.001).The patient satisfaction was the highest in group C(P<0.001).After treatment,the levels of tumor necrosis factorα(TNF-α)and interleukin(IL)-6 in the synovial fluid decreased in each group compared with before(P<0.001),while the levels of IL-10 increased(P<0.001).The three groups differed significantly in the levels of TNF-a,IL-6 and IL-10 in the synovial fluid after treatment(P<0.001).CONCLUSION For patients with early knee osteoarthritis,intra-articular injection of parecoxib could effectively improve clinical symptoms.This method may be a reliable alternative for early knee osteoarthritis.展开更多
Tetramethylpyrazine(TMP) is a traditional Chinese herbal medicine with strong antiinflammatory and cartilage protection activities, and thus a promising candidate for treating osteoarthritis. However, TMP is rapidly c...Tetramethylpyrazine(TMP) is a traditional Chinese herbal medicine with strong antiinflammatory and cartilage protection activities, and thus a promising candidate for treating osteoarthritis. However, TMP is rapidly cleared from the joint cavity after intra-articular injection and requires multiple injections to maintain efficacy. The aim of this study was to encapsulate TMP into poly(lactic-co-glycolic acid)(PLGA) microspheres to enhance the TMP retention in the joint, reducing injection frequencies and decreasing dosage. TMP microspheres were prepared by emulsion/solvent evaporation method. The intra-articular retention of the drug was assessed by detecting the drug concentration distributed in the joint tissue at different time points. The therapeutic effect of TMP microspheres was evaluated by the swelling of knee joints and histologic analysis in papain-induced OA rat model. The prepared freezedried microspheres with a particle size of about 10 μm can effectively prolong the retention time of the drug in the articular cavity to 30 d, which is 4.7 times that of the TMP solution.Intra-articular injection of TMP microspheres efficiently relieved inflammatory symptoms,improved joint lesions and decreased the depletion of proteoglycan. In conclusion, intraarticular injection of TMP loaded microspheres was a promising therapeutic method in the treatment of OA.展开更多
基金Open access funding provided by Manipal Academy of Higher Education,Manipal.
文摘Osteoarthritis is a common aging-related disorder that is confined mostly to the chondral layer of joints(e.g., the knee) but can spread to bony layers over time. In its early stages, osteoarthritis has minimal symptoms;however, these gradually worsen over time and include joint pain, stiffness, loss of mobility, and inflammation. The exposed subchondral bone of a Grade 4 osteoarthritic knee is highly prone to erosion if left untreated due to persistent rubbing between the bones, which can lead to painful bone spurs. However, treating osteoarthritis is especially challenging due to the poor mitotic potential and low metabolic activity of chondrocytes. Although currently available tissue-engineered products(e.g., BST-CarGel■, TruFit■, and Atelocollagen■) can achieve structural reconstruction and tissue regeneration, final clinical outcomes can still be improved. Major challenges faced during clinical studies of tissue-engineered constructs include chondrocyte hypertrophy and the development of mechanically inferior fibrous tissue, among others. These issues can be addressed by selecting suitable biomaterial combinations, mimicking the three-dimensional(3D) architecture of the tissue matrix, and better controlling inflammation. Furthermore, it is crucial to generate essential signaling molecules within the articular cartilage ecosystem. This approach must also account for the microarchitecture of the affected joint and support the chondrogenic differentiation of mesenchymal stem cells. The use of tissue-engineered constructs has the potential to overcome each of these challenges, since materials can be modified for drug/biomolecule delivery while simultaneously facilitating the regeneration of robust articular cartilage. Three-dimensional printing has been successfully used in tissue engineering to achieve bioprinting. By manipulating conventional 3D printing techniques and the types of bioink used, many different types of bioprinting have emerged. Overall, these bioprinting techniques can be used to address various challenges associated with osteoarthritis treatment.
基金supported by the Shandong Provincial Natural Science Foundation(for the preparation of bionic scaffolds for bone and cartilage repair and their osteogenic wear resistance study)(ZR2022ME086).
文摘The primary objective of Cartilage Tissue Engineering(CTE)involves repairing or rebuilding impaired cartilage in an effort to restore joint functionality and enhance patients'quality of life.In this field,researchers are constantly exploring new materials and technologies to address the challenges posed by cartilage damage.Biomimetic hydrogels present several distinct advantages in articular cartilage repair when compared to conventional treatment methods like minimally invasive surgery,joint replacement,and drug therapies.These hydrogels effectively mimic the mechanical characteristics of natural cartilage while also promoting cell adhesion,proliferation,and differentiation through the inclusion of bioactive factors.This results in the creation of high-performance biomaterials,positioning them as a particularly promising therapeutic option.Recently,researchers have drawn inspiration from the intricate structures found in soft tissues to develop various types of biomimetic hydrogels.These innovative hydrogels find applications across various fields,such as biomedicine,tissue engineering,and flexible electronics.In tissue engineering,these materials serve as optimal scaffolds for cartilage regeneration and aid in restoring tissue function.Nevertheless,creating and manufacturing biomimetic hydrogels with complex designs,strong mechanical properties,and multifunctionality poses significant challenges.This paper reviews existing studies on natural and synthetic matrices for biomimetic hydrogels,explores the similarities between these hydrogels and natural cartilage,examines their biological and physical characteristics,discusses their advantages and limitations,and suggests future research avenues.
基金Shaanxi Province Key R&D Program (2022SF-238)Chinese Medicine Pharmaceutical Key Discipline of Shaanxi province (303061107)+1 种基金Discipline Innovation team Project of Shaanxi University of Chinese Medicine (2019-YL11)Shaanxi Province Key subject of pharmacy engineering of Shaanxi Provincial Traditional Chinese Medicine administration (2017001)。
文摘OBJECTIVE: To corroborate the efficacy of Jintiange capsules(JTGs)( 金天格胶囊) in the treatment of osteoarthritis(OA) by exploring the potential mechanism of action of synovial mesenchymal stem cell exosomes(SMSC-Exos) and articular chondrocytes(ACs) through transcriptome sequencing(RNA-seq). METHODS: Type Ⅱ collagenase was used to induce OA in rats. The efficacy of JTGs was confirmed by macroscopic observation of articular cartilage, micro-CT observation, and safranin fast green staining. After SMSC-Exos and ACs were qualified, RNA-seq was used to screen differentially expressed mi RNAs and m RNAs. The target genes of differentially expressed mi RNAs in Synovial mesenchymal stem cells(SMSCs) were predicted based on the multi Mi R R package. The codifferentially expressed genes of SMSC-Exos and ACs were obtained by venny 2.1.0. The mi RNA-m RNA regulatory network was constructed by Cytoscape software. Based on the Omic Share platform, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed on the m RNA regulated by key mi RNAs. Expression trend analysis was performed for co-differentially expressed genes. Correlation analysis was performed on micro-CT efficacy indicators, co-differentially expressed genes mRNA and miRNA. RESULTS: The efficacy of each administration group of JTGs was significant compared with the model group. SMSC-Exos and ACs were identified by their characteristics. The expression of rno-mi R-23a-3p, rnomi R-342-3p, rno-miR-146b-5p, rno-miR-501-3p, rnomiR-214-3p was down-regulated in OA pathological state, and the expression of rno-mi R-222-3p, rno-mi R-30e-3p, rno-mi R-676, and rno-miR-192-5p expression was upregulated, and the expression of all these mi RNAs was reversed after the intervention with JTGs containing serum. The co-differentially expressed genes were enriched in the interleukin 17 signaling pathway, tumor necrosis factor signaling pathway, transforming growth factor-β signaling pathway, etc. The expression trends of Ccl7, Akap12, Grem2, Egln3, Arhgdib, Ccl20, Mmp12, Pla2g2a, and Nr4a1 were significant. There was a correlation between micro-CT pharmacodynamic index, m RNA, and mi RNA. CONCLUSION: JTGs can improve the degeneration of joint cartilage and achieve the purpose of cartilage protection, which can be used for the treatment of OA. SMSCs-related mi RNA expression profiles were significantly altered after the intervention with JTGs containing serum. The 9 co-differentially expressed genes may be the key targets for the efficacy of JTGs in the treatment of OA rats, which can be used for subsequent validation.
基金supported by National Natural Science Foundation of China(Grant No.51975296).
文摘Cartilage regeneration and repair are considered clinical challenges since cartilage has limited capability for reconstruction.Although tissue-engineered materials have the ability to repair cartilage,they have weak mechanical characteristics and cannot resist long-term overload.On the other hand,surgery to replace the joint is frequently done to treat significant cartilage deterioration these days.However,the materials that are being used for replacement have high friction coefficients,lack shock absorption functions,and lack cushioning.Further research on natural articular cartilage structure and function may lead to bionic hydrogels,which have suitable physicochemical and biological characteristics(e.g.,tribological and mechanical properties and the ability to support loadbearing capability),but need improvements.Based on their tribological and mechanical characteristics,the current review highlights the most recent advancements of bionic hydrogels used for articular cartilage,highlighting both the field's recent progress and its potential for future research.For this reason,firstly,some important property improvement methods of bionic hydrogels are discussed and then,the recent findings of various research on the making of those bionic materials are provided and compared.It seems that by using some modifications such as product design,surface treatments,animal tests,controlling the isoelectric point of hydrogels,and computer simulation,the intended mechanical and tribological characteristics of natural articular cartilage may be attained by the bionic hydrogels.
文摘PRIMARY synovial chondromatosis is a rarecondition in which foci of cartilage develop in thesynovial membrane of joints, bursae and tendonsheaths. It typically involves a single large jointin a young adult male.1 The ectopic foci of cartilage canresult in painful joint effusion, and the generation of loosebodies can cause mechanical symptoms.2,3 The etiology ofprimary synovial chondromatosis remains unknown, butmetaplastic theory is the most popular hypothesis. Thecommonly involved joints are knee, elbow, and hip.^4 Theshoulder is a rare site of synovial chondromatosis2,3,5 andthe extra-articular involvement even rarer, with only fewcases presented in literature. This report presents a rarecase of primary combined intra-articular andextra-articular synovial chondromatosis of shoulder jointtreated with arthroscopy.
基金This work was supported by the National Key Program on Basic Research of China (No. 2006BAI23B01-3)National Natural Scie- nce Foundation of China (No. 30430350, 30500)National High-Tech Research and Development Program (No. 2006AA 02Z168, Z000 6303041231).
文摘It has been previously reported that small mother against decapentaplegic 3 （Smad3） gene knockout （Smad3^ex8/ex8） mice displays phenotypes similar to human osteoarthritis, as characterized by abnormal hypertrophic differentiation of articular chondrocytes. To further clarify the crucial target genes that mediate transformation growth factor-β （TGF-β）/Smad3 signals on articular chondrocytes differentiation and investigate the underlying molecular mechanism of osteoarthritis, microarrays were used to perform comparative transcriptional profiling in the articular cartilage between Smad3^ex8/ex8and wild-type mice on day five after birth. The gene profding results showed that the activity of bone morphogenetic protein （BMP） and TGF-β/cell division cycle 42 （Cdc42） signaling pathways were enhanced in Smad3^ex8/ex8 chondrocytes. Moreover, there was altered gene expression in growth hormone/insulin-like growth factor 1 （Igfl） axis and fibroblast growth factor （Fgf） signaling pathway. Notably, protein synthesis related genes and electron transport chain related genes were upregulated in Smad3^ex8/ex8 chondrocytes, implying that accelerated protein synthesis and enhanced cellular respiration might contribute to hypertrophic differentiation of articular chondrocytes and the pathogenesis of osteoarthritis.
文摘<strong>Introduction:</strong> Purpose to study prevalence of the intraarticular chondral lesion in the malleolar fracture by using ankle arthroscopy to fully understand the severity and complexity of the injury. <strong>Methods:</strong> Cross sectional study of 32 patients diagnosed with ankle fracture and undergone open reduction and internal fixation with arthroscopic assessment performed stimultaneously. The mechanism of injury, patterns of injury and intraarticular chondral injury were documented. <strong>Results:</strong> Mean age was 38 years (SD = 14.1, range 18 - 68 years). Eighteen were female and 14 were male. Fifteen involved syndesmostic distruption, 22 had Danis-Weber B injury and 16 had supination external rotation (SER). Ten (31.2%) had positive intraoperative cartilage injury. Significant correlation between the Lauge-Hansen classifications with positive findings with 6 had SER, 2 had pronation adduction and 2 had pronation external rotation.<strong> Conclusion: </strong>The prevalence of chondral injury in ankle fracture was quite high and may leads to poor outcome. Arthroscopy procedure allow surgeon to assess intraarticular surface and reduction of the ankle fracture which prompt further intervention that may improve the clinical outcomes and prognosis of the patients.
文摘Since articular cartilage possesses only a weak capac-ity for repair, its regeneration potential is considered one of the most important challenges for orthopedic surgeons. The treatment options, such as marrow stimulation techniques, fail to induce a repair tissue with the same functional and mechanical properties of native hyaline cartilage. Osteochondral transplantation is considered an effective treatment option but is as-sociated with some disadvantages, including donor-site morbidity, tissue supply limitation, unsuitable mechani-cal properties and thickness of the obtained tissue. Although autologous chondrocyte implantation results in reasonable repair, it requires a two-step surgical pro-cedure. Moreover, chondrocytes expanded in culture gradually undergo dedifferentiation, so lose morpho-logical features and specialized functions. In the search for alternative cells, scientists have found mesenchymal stem cells(MSCs) to be an appropriate cellular mate-rial for articular cartilage repair. These cells were origi-nally isolated from bone marrow samples and further investigations have revealed the presence of the cells in many other tissues. Furthermore, chondrogenic dif-ferentiation is an inherent property of MSCs noticedat the time of the cell discovery. MSCs are known to exhibit homing potential to the damaged site at which they differentiate into the tissue cells or secrete a wide spectrum of bioactive factors with regenerative proper-ties. Moreover, these cells possess a considerable im-munomodulatory potential that make them the general donor for therapeutic applications. All of these topics will be discussed in this review.
基金Supported by Russian Foundation for Basic Research,No.14-4 4-00010
文摘AIM To determine peculiarities of tissue responses to manual and automated Ilizarov bone distraction in nerves and articular cartilage.METHODS Twenty-nine dogs were divided in two experimental groups: Group M-leg lengthening with manual distraction(1 mm/d in 4 steps), Group A-automated distraction(1 mm/d in 60 steps) and intact group. Animals were euthanized at the end of distraction, at 30 th day of fixation in apparatus and 30 d after the fixator removal. M-responses in gastrocnemius and tibialis anterior muscles were recorded, numerical histology of peronealand tibialis nerves and knee cartilage semi-thin sections, scanning electron microscopy and X-ray electron probe microanalysis were performed.RESULTS Better restoration of M-response amplitudes in leg muscles was noted in A-group. Fibrosis of epineurium with adipocytes loss in peroneal nerve, subperineurial edema and fibrosis of endoneurium in some fascicles of both nerves were noted only in M-group, shares of nerve fibers with atrophic and degenerative changes were bigger in M-group than in A-group. At the end of experiment morphometric parameters of nerve fibers in peroneal nerve were comparable with intact nerve only in A-group. Quantitative parameters of articular cartilage(thickness, volumetric densities of chondrocytes, percentages of isogenic clusters and empty cellular lacunas, contents of sulfur and calcium) were badly changed in M-group and less changed in A-group.CONCLUSION Automated Ilizarov distraction is more safe method of orthopedic leg lengthening than manual distraction in points of nervous fibers survival and articular cartilage arthrotic changes.
基金supported by RGC Themebased Research Scheme of Hong Kong (T13-402/17N)National Natural Science Foundation of China (81802152)+5 种基金Natural Science Foundation of Guangdong Province (2019A1515012224)RGC Areas of Excellence (AoE/M-402/20)RGC Collaborative Research Fund (C4026-17WF)General Research Fund (14121918 and 14173917)the Innovation and Technology Commission Funding (ITS/208/18FX)Key-Area Research and Development Program of Guangdong Province (2019B010941001)。
文摘Osteoarthritis is the most prevalent chronic and debilitating joint disease,resulting in huge medical and socioeconomic burdens.Intra-articular administration of agents is clinically used for pain management.However,the effectiveness is inapparent caused by the rapid clearance of agents.To overcome this issue,nanoparticles as delivery systems hold considerable promise for local control of the pharmacokinetics of therapeutic agents.Given the therapeutic programs are inseparable from pathological progress of osteoarthritis,an ideal delivery system should allow the release of therapeutic agents upon specific features of disorders.In this review,we firstly introduce the pathological features of osteoarthritis and the design concept for accurate localization within cartilage for sustained drug release.Then,we review the interactions of nanoparticles with cartilage microenvironment and the rational design.Furthermore,we highlight advances in the therapeutic schemes according to the pathology signals.Finally,armed with an updated understanding of the pathological mechanisms,we place an emphasis on the development of“smart”bioresponsive and multiple modality nanoparticles on the near horizon to interact with the pathological signals.We anticipate that the exploration of nanoparticles by balancing the efficacy,safety,and complexity will lay down a solid foundation tangible for clinical translation.
基金supported by the National Natural Science Foundation of China(10772018,30872720)
文摘It is well known that subtle changes in structure and tissue composition of articular cartilage can lead to its degeneration. The present paper puts forward a modified layered inhomogeneous triphasic model with four parameters based on the inhomogeneous triphasic model proposed by Narmoneva et al. Incorporating a piecewise fitting optimization criterion, the new model was used to obtain the uniaxial modulus Ha, and predict swelling pattern for the articular cartilage based on ultrasound-measured swelling strain data. The results show that the new method can be used to provide more accurate estimation on the uniaxial modulus than the inhomogeneous triphasic model with three parameters and the homogeneous mode, and predict effectively the swell- ing strains of highly nonuniform distribution of degenerated articular cartilages. This study can provide supplementary information for exploring mechanical and material properties of the cartilage, and thus be helpful for the diagnosis of osteoarthritis-related diseases.
基金supported by the National Natural Science Foundation of China(Nos.81171472,81201407,and 81071270)the Innovation Team Project of Sichuan Provincial Education Department(No.13TD0030)+1 种基金the Major Transformation Cultivation Project of Sichuan Provincial Education Department(No.15CZ0021)the Science and Technology Project of Nanchong City(No.14A0021),China
文摘Objective： In our previous work, we prepared a type of chitosan hydrogel with excellent biocompatibility. In this study, tissue-engineered cartilage constructed with this chitosan hydrogel and costal chondrocytes was used to repair the articular cartilage defects. Methods： Chitosan hydrogels were prepared with a crosslinker formed by combining 1,6-diisocyanatohexane and polyethylene glycol. Chitosan hydrogel scaffold was seeded with rabbit chondrocytes that had been cultured for one week in vitro to form the preliminary tissue-engineered cartilage. This preliminary tissue-engineered cartilage was then transplanted into the defective rabbit articular cartilage. There were three treatment groups： the experimental group received preliminary tissue-engineered cartilage; the blank group received pure chitosan hydrogels; and, the control group had received no implantation. The knee joints were harvested at predetermined time. The repaired cartilage was analyzed through gross morphology, histologically and immunohistochemically. The repairs were scored according to the international cartilage repair society （ICRS） standard. Results： The gross morphology results suggested that the defects were repaired completely in the experimental group after twelve weeks. The regenerated tissue connected closely with subchondral bone and the boundary with normal tissue was fuzzy. The cartilage lacuna in the regenerated tissue was similar to normal cartilage lacuna. The results of ICRS gross and histological grading showed that there were significant differences among the three groups （P〈0.05）. Conclusions： Chondrocytes implanted in the scaffold can adhere, proliferate, and secrete extracellular matrix. The novel tissue-engineered cartilage constructed in our research can completely repair the structure of damaged articular cartilage.
基金supported by the National Natural Science Foundation of China(Grant No.81071131)Beijing Talents Fund(Grant No.2015000021467G177)
文摘Objective Using MR T2-mapping and histopathologic score for articular cartilage to evaluate the effect of structural changes in subchondral bone on articular cartilage. Methods Twenty-four male Beagle dogs were randomly divided into a subchondral bone defect group （n = 12） and a bone cement group （n = 12）. Models of subchondral bone defectin the medial tibial plateau and subchondral bone filled with bone cement were constructed. In all dogs, the left knee joint was used as the experimental sideand the right knee as the sham side. The T2 value for articular cartilage at the medial tibial plateau was measured at postoperative weeks 4, 8, 16, and 24. The articular cartilage specimens were stained with hematoxylin and eosin, and evaluated using the Mankin score. Results There was a statistically significant difference （P 〈 0.05） in Mankin score between the bone defect group and the cement group at postoperative weeks 16 and 24. There was a statistically significant difference in the T2 values between the bone defect group and its sham group （P 〈 0.05） from week 8, and between the cement group and its sham group （P 〈 0.05） from week 16. There was significant difference in T2 values between the two experimental groups at postoperative week 24 （P 〈 0.01）. The T2 value for articular cartilage was positively correlated with the Mankin score （ρ = 0.758, P 〈 0.01）. Conclusion Structural changes in subchondral bone can lead to degeneration of the adjacent articular cartilage. Defects in subchondral bone cause more severe degeneration of cartilage than subchondral bone filled with cement. The T2 value for articular cartilage increases with the extent of degeneration. MR T2-mapping images and the T2 value for articular cartilage can indicate earlycartilage degeneration.
基金supported by the National Natural Science Foundation of China (No. 50606032)the Graduate Innovation Research Program of Zhejiang Province (No. YK2008020), China
文摘Osteochondral allografting has been proved to be a useful method to treat diseased or damaged areas of joint surfaces. Operational long-term stocks of grafts which supply a buffer between procurement and utilization would contribute to the commercialization or industrialization of this technology. Vitrification has been thought to be a promising method for successful preservation of articular cartilage （AC）, but high concentration cryoprotectants （CPAs） are used which may cause high cellular toxicity. An effective way to reduce CPA toxioity is to increase CPA concen- tration gradually while the temperature is lowered. Understanding the mechanism of （31~A permeation at subzero temperatures is important for designing the cryopreservation protocol. In this research, the permeation of dimethyl sulfoxide （MezSO） in ovine AC at subzero temperatures was studied experimentally. Pretreated AC discs were ex- posed in Me2SO solutions for different time （0, 5, 15, 30, 50, 80, and 120 min） at three temperature levels （-10, -20, and -30℃）. The Me2SO concentration within the tissue was determined by ultraviolet （UV） spectrophotometry. The diffusion coefficients were estimated to be 0.85×10-6, 0.48×10-8, and 0.27×10-6 cm2/s at -10, -20, and -,30℃, respectively, and the corresponding activation energy was 29.23 kJ/mol. Numerical simulation was performed to com- pare two Me2SO addition protocols, and the results demonstrated that the total loading duration could be effectively reduced with the knowledge of permeation kinetics.
基金supported by grants from the AO Foundation (AOOCD Consortium TA1711481)Areas of Excellence Scheme from the University Grant Council of Hong Kong (Ao E/M-402/20)+1 种基金Theme-based Research Scheme from the University Grant Council of Hong Kong (T13-402/17-N)Key-Area Research and Development Program of Guangdong Province (2019B010941001)
文摘Articular cartilage(AC)is an avascular and flexible connective tissue located on the bone surface in the diarthrodial joints.AC defects are common in the knees of young and physically active individuals.Because of the lack of suitable tissue-engineered artificial matrices,current therapies for AC defects,espe-cially full-thickness AC defects and osteochondral interfaces,fail to replace or regenerate damaged carti-lage adequately.With rapid research and development advancements in AC tissue engineering(ACTE),functionalized hydrogels have emerged as promising cartilage matrix substitutes because of their favor-able biomechanical properties,water content,swelling ability,cytocompatibility,biodegradability,and lubricating behaviors.They can be rationally designed and conveniently tuned to simulate the extracel-lular matrix of cartilage.This article briefly introduces the composition,structure,and function of AC and its defects,followed by a comprehensive review of the exquisite(bio)design and(bio)fabrication of func-tionalized hydrogels for AC repair.Finally,we summarize the challenges encountered in functionalized hydrogel-based strategies for ACTE both in vivo and in vitro and the future directions for clinical translation.
基金This paper was supported by the National Natural Science Foundation of China （Grant No： 50875201） and the National Hi-Tech Program of China （Grant No： 2009AA043801）. The authors thank Professor Yiping Tang from Xi＇an Jiaotong University for improving the manuscript.
文摘For improving the theory of gradient microstructure of cartilage/bone interface, human distal femurs were studied. Scanning Electron Microscope （SEM）, histological sections and MicroCT were used to observe, measure and model the micro- structure of cartilage/bone interface. The results showed that the cartilage/bone interface is in a hierarchical structure which is composed of four different tissue layers. The interlocking of hyaline cartilage and calcified cartilage and that of calcified car- tilage and subchondral bone are in the manner of＂protrusion-pore＂ with average diameter of 17.0 gm and 34.1 lam respectively. In addition, the cancellous bone under the cartilage is also formed by four layer hierarchical structure, and the adjacent layers are connected by bone trabecula in the shape of H, I and Y, forming a complex interwoven network structure. Finally, the simplified structure model of the cartilage/bone interface was proposed according to the natural articular cartilage/bone interface. The simplified model is a 4-layer gradient biomimetic structure, which corresponds to four different tissues of natural cartilage/bone interface. The results of this work would be beneficial to the design of bionic scaffold for the tissue engineering of articular cartilage/bone.
文摘BACKGROUND Inflammatory cytokines play a vital role in the occurrence of osteoarticular injury and inflammation. Whether inflammation-associated factors interleukin-1β(IL- 1β), IL-6, tumor necrosis factor-α(TNF-α) and vascular endothelial growth factor (VEGF) are involved in the pathogenesis of keen articular cartilage injury remains poorly understood. AIM To measure the levels of inflammatory factors [IL-1β, IL-6, TNF-α and VEGF] in patients with knee articular cartilage injury. METHODS Fifty-five patients with knee articular cartilage injury were selected as patient groups, who were divided into three grades [mild (n = 20), moderate (n = 19) and severe (n = 16)] according to disease severity and X-ray examinations. Meanwhile, 30 healthy individuals who underwent physical examination were selected as the control group. The levels of IL-1β, IL-6, TNF-α and VEGF were measured by ELISA and immunohistochemical staining. RESULTS Compared with the control group, patient groups displayed significantly higher levels of IL-1β, IL-6, TNF-α and VEGF, and the extent of increase was directly proportional to the severity of injury (P < 0.05). In addition, the number of cells with positive staining of IL-1β, IL-6, TNF-α and VEGF in the synovial membrane were significantly increased, along with increased disease severity (P < 0.05). After treatment, the scores of visual analogue scale and the Western Ontario and McMaster University of Orthopaedic Index in patient groups were 2.26 ± 1.13 and 15.56 ± 7.12 points, respectively, which were significantly lower than those before treatment (6.98 ± 1.32 and 49.48 ± 8.96). Correlation analysis suggested that IL-1β and TNF-α were positively correlated with VEGF. CONCLUSION IL-1β, IL-6, TNF-α and VEGF levels are increased in patients with knee articular cartilage injury, and are associated with the disease severity, indicating they might play an important role in the occurrence and development of knee articular cartilage injury. Furthermore, therapeutically targeting them might be a novel approach for the treatment of keen articular cartilage injury.
基金supported by the National Natural Science Foundation of China (31170896)State Key Laboratory of Software Development Environment (SKLSDE-2011ZX-11)
文摘The microgravity environment of a long-term space flight may induce acute changes in an astronaut＇s musculo-skeletal systems. This study explores the effects of simulated microgravity on the mechanical characteristics of articular cartilage. Six rats underwent tail suspension for 14 days and six additional rats were kept under normal earth gravity as controls. Swelling strains were measured using high-frequency ultrasound in all cartilage samples subject to osmotic loading. Site-specific swelling strain data were used in a triphasic theoretical model of cartilage swelling to determine the uniaxial modulus of the cartilage solid matrix. No severe surface irregularities were found in the cartilage samples obtained from the control or tail-suspended groups. For the tail-suspended group, the thickness of the cartilage at a specified site, as determined by ultrasound echo, showed a minor decrease. The uniaxial modulus of articular cartilage at the specified site decreased significantly, from （6.31 ± 3.37） MPa to （5.05 ± 2.98）MPa （p 〈 0.05）. The histology- stained image of a cartilage sample also showed a reduced number of chondrocytes and decreased degree of matrix staining. These results demonstrated that the 14 d simulated microgravity induced significant effects on the mechanical characteristics of articular cartilage. This study is the first attempt to explore the effects of simulated microgravity on the mechanical characteristics of articular cartilage using an osmotic loading method and a triphasic model. The conclusions may provide reference information for manned space flights and a better understanding of the effects of microgravity on the skeletal system.
基金National Natural Science Foundation of China,NO.81774274Project of Jiangsu Provincial Hospital of Traditional Chinese Medicine,NO.Y19058
文摘BACKGROUND Non-steroid anti-inflammatory drugs(NSAIDs)have played a crucial role in the treatment of osteoarthritis,especially in the early stages.However,the cardiovascular risk and adverse gastrointestinal reactions of oral NSAIDs in elderly people cannot be underestimated.Intra-articular injection of NSAIDs may be a new attempt for early knee osteoarthritis treatment.Parecoxib may be a suitable drug for intra-articular injection.AIM To observe the clinical efficacy of the intra-articular injection of parecoxib for early knee osteoarthritis.METHODS Early knee osteoarthritis patients(n=110)were retrospectively analyzed.These patients were divided into three groups:Basic treatment+oral glucosamine(group A,n=37),oral celecoxib+basic treatment+oral glucosamine(group B,n=37),and intra-articular injection of parecoxib+basic treatment+oral glucosamine(group C,n=36).Intra-articular injection of parecoxib was performed once every 2 wk at a dose of 40 mg each time,for three times total.The three groups were compared in terms of visual analogue scale(VAS)scores,Hospital for Special Surgery(HSS)scores and patient satisfaction before and after treatment.The levels of inflammatory cytokines in the synovial fluid were detected in the three groups before and after treatment.RESULTS All patients were followed up for an average of 15.5±2.7 mo.The clinical efficacy was estimated by VAS and HSS scores at 12 mo after treatment.Inflammatory cytokine levels in the synovial fluid were evaluated at 3 mo after treatment.VAS and HSS scores were significantly improved in each group compared with before(P<0.001).There were significant differences among the three groups in VAS and HSS scores(P<0.001).The clinical efficacy of group C was superior to that of groups A and B(P<0.001),while group B outperformed group A in this respect(P<0.001).The patient satisfaction was the highest in group C(P<0.001).After treatment,the levels of tumor necrosis factorα(TNF-α)and interleukin(IL)-6 in the synovial fluid decreased in each group compared with before(P<0.001),while the levels of IL-10 increased(P<0.001).The three groups differed significantly in the levels of TNF-a,IL-6 and IL-10 in the synovial fluid after treatment(P<0.001).CONCLUSION For patients with early knee osteoarthritis,intra-articular injection of parecoxib could effectively improve clinical symptoms.This method may be a reliable alternative for early knee osteoarthritis.
文摘Tetramethylpyrazine(TMP) is a traditional Chinese herbal medicine with strong antiinflammatory and cartilage protection activities, and thus a promising candidate for treating osteoarthritis. However, TMP is rapidly cleared from the joint cavity after intra-articular injection and requires multiple injections to maintain efficacy. The aim of this study was to encapsulate TMP into poly(lactic-co-glycolic acid)(PLGA) microspheres to enhance the TMP retention in the joint, reducing injection frequencies and decreasing dosage. TMP microspheres were prepared by emulsion/solvent evaporation method. The intra-articular retention of the drug was assessed by detecting the drug concentration distributed in the joint tissue at different time points. The therapeutic effect of TMP microspheres was evaluated by the swelling of knee joints and histologic analysis in papain-induced OA rat model. The prepared freezedried microspheres with a particle size of about 10 μm can effectively prolong the retention time of the drug in the articular cavity to 30 d, which is 4.7 times that of the TMP solution.Intra-articular injection of TMP microspheres efficiently relieved inflammatory symptoms,improved joint lesions and decreased the depletion of proteoglycan. In conclusion, intraarticular injection of TMP loaded microspheres was a promising therapeutic method in the treatment of OA.
