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
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
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
Type 2 diabetes (T2D) is associated with systemic abnormal bone remodeling and bone loss. Meanwhile, abnormal subchondral bone remodeling induces cartilage degradation, resulting in osteoarthritis (OA). Accordingl...Type 2 diabetes (T2D) is associated with systemic abnormal bone remodeling and bone loss. Meanwhile, abnormal subchondral bone remodeling induces cartilage degradation, resulting in osteoarthritis (OA). Accordingly, we investigated alterations in subchondral bone remodeling, microstructure and strength in knees from T2D patients and their association with cartilage degradation. Tibial plateaus were collected from knee OA patients undergoing total knee arthroplasty and divided into non-diabetic (n---70) and diabetes (n = 51) groups. Tibial plateaus were also collected from cadaver donors (n = 20) and used as controls. Subchondral bone microstructure was assessed using micro-computed tomography. Bone strength was evaluated by micro-finite-element analysis. Cartilage degradation was estimated using histology. The expression of tartrate-resistant acidic phosphatase (TRAP), osterix, and osteocalcin were calculated using immunohistochemistry. Osteoarthritis Research Society International (OARSI) scores of lateral tibial plateau did not differ between non-diabetic and diabetes groups, while higher OARSI scores on medial side were detected in diabetes group. Lower bone volume fraction and trabecular number and higher structure model index were found on both sides in diabetes group. These microstructural alterations translated into lower elastic modulus in diabetes group. Moreover, diabetes group had a larger number of TRAP~ osteoclasts and lower number of Osterix~ osteoprogenitors and Osteocalcin~ osteoblasts. T2D knees are characterized by abnormal subchondral bone remodeling and microstructural and mechanical impairments, which were associated with exacerbated cartilage degradation. In regions with intact cartilage the underlying bone still had abnormal remodeling in diabetes group, suggesting that abnormal bone remodeling may contribute to the early pathogenesis of T2D-associated knee OA.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
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
The normal displacement of articular cartilage was measured under load and in sliding, and the coefficient of friction during sliding was measured using a UMT-2 Multi-Specimen Test System. The maximum normal displacem...The normal displacement of articular cartilage was measured under load and in sliding, and the coefficient of friction during sliding was measured using a UMT-2 Multi-Specimen Test System. The maximum normal displacement under load and the start-up frictional coefficient have similar tendency of variation with loading time. The sliding speed does not significantly influence the frictional coefficient of articular cartilage.展开更多
The articular cartilage (AC) can be seen as a biphasic poroelastic material. The cartilage deformation under compression mainly leads to an interstitial fluid flow in the porous solid phase. In this paper, an analyt...The articular cartilage (AC) can be seen as a biphasic poroelastic material. The cartilage deformation under compression mainly leads to an interstitial fluid flow in the porous solid phase. In this paper, an analytical poroelastic model for the AC under laboratorial mechanical testing is developed. The solutions of interstitial fluid pressure and velocity are obtained. The results show the following facts. (i) Both the pressure and fluid velocity amplitudes are proportional to the strain loading amplitude. (ii) Both the amplitudes of pore fluid pressure and velocity in the AC depend more on the loading amplitude than on the frequency. Thus, in order to obtain the considerable fluid stimulus for the AC cell responses, the most effective way is to increase the loading amplitude rather than the frequency. (iii) Both the interstitiM fluid pressure and velocity are strongly affected by permeability variations. This model can be used in experimental tests of the parameters of AC or other poroelastic materials, and in research of mechanotransduction and injury mechanism involved interstitial fluid flow.展开更多
Two discriminant methods,partial least squares-discriminant analysis(PLS-DA)and Fisher's discriminant analysis(FDA),were combined with Fourier transform infrared imaging(FTIRI)to differentiate healthy and osteoart...Two discriminant methods,partial least squares-discriminant analysis(PLS-DA)and Fisher's discriminant analysis(FDA),were combined with Fourier transform infrared imaging(FTIRI)to differentiate healthy and osteoarthritic articular cartilage in a canine model.Osteoarthritic cartilage had been developed for up to two years after the anterior cruciate ligament(ACL)transection in one knee.Cartilage specimens were sectioned into 10μm thickness for FTIRI.A PLS-DA model was developed after spectral pre-processing.All IR spectra extracted from FTIR images were calculated by PLS-DA with the discriminant accuracy of 90%.Prior to FDA,principal component analysis(PCA)was performed to decompose the IR spectral matrix into informative princi pal component matrices.Based on the different discriminant mechanism,the discriminant accuracy(96%)of PCA-FDA with high convenience was higher than that of PLS-DA.No healthy cartilage sample was mis assigned by these two methods.The above mentioned suggested that both integrated technologies of FTIRI-PLS-DA and,especially,FTIRI-PCA-FDA could become a promising tool for the discrimination of healthy and osteoarthritic cartilage specimen as well as the diagnosis of cartilage lesion at microscopic level.The results of the study would be helpful for better understanding the pathology of osteoarthritics.展开更多
Objective: To observe the expression of TGF-β and TNF-α in the spinal cord injured rat model and discuss the significance of the articular cartilage metabolism. Methods: 36 SD female rats were randomly divided int...Objective: To observe the expression of TGF-β and TNF-α in the spinal cord injured rat model and discuss the significance of the articular cartilage metabolism. Methods: 36 SD female rats were randomly divided into 2 groups: Rats models of spinal cord injury were implemented by Allen method. T10 laminectomy was performed in the control group. Both groups of rats were killed respectively in 1w, 3w and 6w. Hematoxylin-eosin stain was given to each slice in the model group and control group. Immunohistochemical stain was applied by using ABC method in the expression of TGF-β and TNF-α. Those expressed level were performed in image analysis and statistics process. Results: TGF-β and TNF-α were mainly distributed on the surface layer of the articular cartilage, with a weak expression in control group. The expression of TNF-α in the model group was more significant than that in the control group in the lw, and still remained an evident difference with that in control group until the 6w(P 〈 0.05). TGF-β expression of the model group had no remarkable difference with the control group in the lw (P 〉 0.05) and prominently became stronger at 6w(P 〈 0.05). Conclusion: The expression of TNF-α occurred early in the development of spinal cord injury, and the expression of TGF-β became stronger with the revival of spinal neural function. Both expressions were strengthened in articular cartilage in the 3rd week.展开更多
Articular cartilage is a layer of low-friction,load-bearing soft hydrated tissue covering bone-ends in diarthrosis,which plays an important role in spreading the load,reducing the joint contact stress,joint friction a...Articular cartilage is a layer of low-friction,load-bearing soft hydrated tissue covering bone-ends in diarthrosis,which plays an important role in spreading the load,reducing the joint contact stress,joint friction and wear during exercise.The vital mechanical function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
The boundary lubrication mechanism at the articulating surface of natural synovial joints has been the subject of much discussion in tribology.In this study,to elucidate the lubricating function of the superficial are...The boundary lubrication mechanism at the articulating surface of natural synovial joints has been the subject of much discussion in tribology.In this study,to elucidate the lubricating function of the superficial area of articular cartilage and synovial fluid(SF),cartilage specimens were processed with four different treatments:gentle and severe washing with detergent,incubation in NaCl solution,and trypsin digestion to selectively remove certain constituents from the cartilage surface.Subsequently,the frictional characteristics were examined in phosphate-buffered saline(PBS)and SF against glass.Angularly reciprocating sliding tests with a spherical glass probe and square articular cartilage specimens were performed at low contact loads in the mN range to extract the frictional behavior in the superficial area of the cartilage specimens.Meanwhile,the cartilage surface was observed to confirm the effects of treatments on the morphology of the cartilage surface using a fluorescence microscope and water-immersion methods.The coefficient of friction(COF)of the prepared cartilage specimens was varied from 0.05 to over 0.3 in PBS.However,a certain group of cartilage specimens exhibited a low COF of less than 0.1 with limited variation.For the low COF group of specimens,all four treatments increased the COF in PBS to different extents,and fluorescence microscopy revealed that the integrity of the cartilage surface was deteriorated by treatments.This means that the intact cartilage surface had lubricating constituents to maintain low friction,and the removal of such constituents resulted in the loss of the intrinsic boundary lubricity of the cartilage surface.The variation in the COF of the cartilage specimens was suppressed in SF because it had a clear boundary lubrication effect on the cartilage surface.The lubricating effect of SF could be confirmed even after degenerative treatment.展开更多
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...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 intraarticular drug delivery systems(DDSs) in the future.展开更多
As a highly specialized shock-absorbing connective tissue,articular cartilage(AC)has very limited self-repair capacity after traumatic injuries,posing a heavy socioeconomic burden.Common clinical therapies for small-t...As a highly specialized shock-absorbing connective tissue,articular cartilage(AC)has very limited self-repair capacity after traumatic injuries,posing a heavy socioeconomic burden.Common clinical therapies for small-to medium-size focal AC defects are well-developed endogenous repair and cell-based strategies,including microfracture,mosaicplasty,autologous chondrocyte implantation(ACI),and matrix-induced ACI(MACI).However,these treatments frequently result in mechanically inferior fibrocartilage,low cost-effectiveness,donor site morbidity,and short-term durability.It prompts an urgent need for innovative approaches to pattern a pro-regenerative microenvironment and yield hyaline-like cartilage with similar biomechanical and biochemical properties as healthy native AC.Acellular regenerative biomaterials can create a favorable local environment for AC repair without causing relevant regulatory and scientific concerns from cell-based treatments.A deeper understanding of the mechanism of endogenous cartilage healing is furthering the(bio)design and application of these scaffolds.Currently,the utilization of regenerative biomaterials to magnify the repairing effect of joint-resident endogenous stem/progenitor cells(ESPCs)presents an evolving improvement for cartilage repair.This review starts by briefly summarizing the current understanding of endogenous AC repair and the vital roles of ESPCs and chemoattractants for cartilage regeneration.Then several intrinsic hurdles for regenerative biomaterials-based AC repair are discussed.The recent advances in novel(bio)design and application regarding regenerative biomaterials with favorable biochemical cues to provide an instructive extracellular microenvironment and to guide the ESPCs(e.g.adhesion,migration,proliferation,differentiation,matrix production,and remodeling)for cartilage repair are summarized.Finally,this review outlines the future directions of engineering the next-generation regenerative biomaterials toward ultimate clinical translation.展开更多
Background Quantitative T2 mapping has been a widely used method for the evaluation, of pathological cartilage properties, and the histological assessment system of osteoarthritis in the rabbit has been published rece...Background Quantitative T2 mapping has been a widely used method for the evaluation, of pathological cartilage properties, and the histological assessment system of osteoarthritis in the rabbit has been published recently. The aim of the study was to investigate the effectiveness of quantitative T2 mapping evaluation for articular cartilage lesions of a rabbit model of anterior cruciate liaament transection (ACLTI osteoarthritis.展开更多
The extremely low friction and minimal wear in natural synovial joints appear to be established by effective lubrication mechanisms based on appropriate combination of articular cartilage and synovial fluid.The comple...The extremely low friction and minimal wear in natural synovial joints appear to be established by effective lubrication mechanisms based on appropriate combination of articular cartilage and synovial fluid.The complex structure of cartilage composed of collagen and proteoglycan with high water content contributes to high load-carrying capacity as biphasic materials and the various constituents of synovial fluid play important roles in various lubrication mechanisms.However,the detailed differences in functions of the intact and damaged cartilage tissues,and the interaction or synergistic action of synovia constituents with articular cartilage have not yet been clarified.In this study,to examine the roles of synovia constituents and the importance of cartilage surface conditions,the changes in friction were observed in the reciprocating tests of intact and damaged articular cartilage specimens against glass plate lubricated with lubricants containing phospholipid,protein and/or hyaluronic acid as main constituents in synovial fluid.The effectiveness of lubricant constituents and the influence of cartilage surface conditions on friction are discussed.In addition,the protectiveness by synovia constituents for intact articular cartilage surfaces is evaluated.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
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 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 National Natural Science Foundation of China(NSFC Nos.81601930 and U1613224)Natural Science Foundation of Guangxi(2016JJB140050)+1 种基金Research Grant Council of Hong Kong(HKU715213 and 17206916)Shenzhen Peacock Project
文摘Type 2 diabetes (T2D) is associated with systemic abnormal bone remodeling and bone loss. Meanwhile, abnormal subchondral bone remodeling induces cartilage degradation, resulting in osteoarthritis (OA). Accordingly, we investigated alterations in subchondral bone remodeling, microstructure and strength in knees from T2D patients and their association with cartilage degradation. Tibial plateaus were collected from knee OA patients undergoing total knee arthroplasty and divided into non-diabetic (n---70) and diabetes (n = 51) groups. Tibial plateaus were also collected from cadaver donors (n = 20) and used as controls. Subchondral bone microstructure was assessed using micro-computed tomography. Bone strength was evaluated by micro-finite-element analysis. Cartilage degradation was estimated using histology. The expression of tartrate-resistant acidic phosphatase (TRAP), osterix, and osteocalcin were calculated using immunohistochemistry. Osteoarthritis Research Society International (OARSI) scores of lateral tibial plateau did not differ between non-diabetic and diabetes groups, while higher OARSI scores on medial side were detected in diabetes group. Lower bone volume fraction and trabecular number and higher structure model index were found on both sides in diabetes group. These microstructural alterations translated into lower elastic modulus in diabetes group. Moreover, diabetes group had a larger number of TRAP~ osteoclasts and lower number of Osterix~ osteoprogenitors and Osteocalcin~ osteoblasts. T2D knees are characterized by abnormal subchondral bone remodeling and microstructural and mechanical impairments, which were associated with exacerbated cartilage degradation. In regions with intact cartilage the underlying bone still had abnormal remodeling in diabetes group, suggesting that abnormal bone remodeling may contribute to the early pathogenesis of T2D-associated knee OA.
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.
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.
文摘The normal displacement of articular cartilage was measured under load and in sliding, and the coefficient of friction during sliding was measured using a UMT-2 Multi-Specimen Test System. The maximum normal displacement under load and the start-up frictional coefficient have similar tendency of variation with loading time. The sliding speed does not significantly influence the frictional coefficient of articular cartilage.
基金Project supported by the National Natural Science Foundation of China(Nos.11632013,11472185,and 11702183)the Natural Science Foundation of Shanxi Province(No.2016021145)+1 种基金the Program for the OIT of Higher Learning Institutions of Shanxi,the State Key Laboratory of Fine Chemicals(No.KF 1511)the Scientific and Technological Innovation Projects of Colleges and Universities in Shanxi Province(No.2017135)
文摘The articular cartilage (AC) can be seen as a biphasic poroelastic material. The cartilage deformation under compression mainly leads to an interstitial fluid flow in the porous solid phase. In this paper, an analytical poroelastic model for the AC under laboratorial mechanical testing is developed. The solutions of interstitial fluid pressure and velocity are obtained. The results show the following facts. (i) Both the pressure and fluid velocity amplitudes are proportional to the strain loading amplitude. (ii) Both the amplitudes of pore fluid pressure and velocity in the AC depend more on the loading amplitude than on the frequency. Thus, in order to obtain the considerable fluid stimulus for the AC cell responses, the most effective way is to increase the loading amplitude rather than the frequency. (iii) Both the interstitiM fluid pressure and velocity are strongly affected by permeability variations. This model can be used in experimental tests of the parameters of AC or other poroelastic materials, and in research of mechanotransduction and injury mechanism involved interstitial fluid flow.
基金the National Natural Science Foundation of China for the grant of 61378087Natural Science Foundation of Jiangsu Province(BK20151478)+1 种基金Zhi-Hua Mao is grateful to the Open Funds for Graduate Innovation Lab of Nanjing University of Aeronautics and Astronautics(kfjj20150309)and Fundamental Research Funds for the Central Universities.The raw data acquisition in FTIRI was mostly carried out in the lab of Professor Yang Xia at Oakland University(Rochester,Michigan,USA).Professor Xia was supported by an NIH grant R01-AR052353 during the time of the data acquisition.
文摘Two discriminant methods,partial least squares-discriminant analysis(PLS-DA)and Fisher's discriminant analysis(FDA),were combined with Fourier transform infrared imaging(FTIRI)to differentiate healthy and osteoarthritic articular cartilage in a canine model.Osteoarthritic cartilage had been developed for up to two years after the anterior cruciate ligament(ACL)transection in one knee.Cartilage specimens were sectioned into 10μm thickness for FTIRI.A PLS-DA model was developed after spectral pre-processing.All IR spectra extracted from FTIR images were calculated by PLS-DA with the discriminant accuracy of 90%.Prior to FDA,principal component analysis(PCA)was performed to decompose the IR spectral matrix into informative princi pal component matrices.Based on the different discriminant mechanism,the discriminant accuracy(96%)of PCA-FDA with high convenience was higher than that of PLS-DA.No healthy cartilage sample was mis assigned by these two methods.The above mentioned suggested that both integrated technologies of FTIRI-PLS-DA and,especially,FTIRI-PCA-FDA could become a promising tool for the discrimination of healthy and osteoarthritic cartilage specimen as well as the diagnosis of cartilage lesion at microscopic level.The results of the study would be helpful for better understanding the pathology of osteoarthritics.
基金This work was supported by the national nature science fundation(30400163)
文摘Objective: To observe the expression of TGF-β and TNF-α in the spinal cord injured rat model and discuss the significance of the articular cartilage metabolism. Methods: 36 SD female rats were randomly divided into 2 groups: Rats models of spinal cord injury were implemented by Allen method. T10 laminectomy was performed in the control group. Both groups of rats were killed respectively in 1w, 3w and 6w. Hematoxylin-eosin stain was given to each slice in the model group and control group. Immunohistochemical stain was applied by using ABC method in the expression of TGF-β and TNF-α. Those expressed level were performed in image analysis and statistics process. Results: TGF-β and TNF-α were mainly distributed on the surface layer of the articular cartilage, with a weak expression in control group. The expression of TNF-α in the model group was more significant than that in the control group in the lw, and still remained an evident difference with that in control group until the 6w(P 〈 0.05). TGF-β expression of the model group had no remarkable difference with the control group in the lw (P 〉 0.05) and prominently became stronger at 6w(P 〈 0.05). Conclusion: The expression of TNF-α occurred early in the development of spinal cord injury, and the expression of TGF-β became stronger with the revival of spinal neural function. Both expressions were strengthened in articular cartilage in the 3rd week.
基金National Natural Science Foundation of China,10872147Natural Science Foundation of Tianjin,09JCYBJC1400
文摘Articular cartilage is a layer of low-friction,load-bearing soft hydrated tissue covering bone-ends in diarthrosis,which plays an important role in spreading the load,reducing the joint contact stress,joint friction and wear during exercise.The vital mechanical function
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.
基金support was given by the Grant-in Aid for Scientific Research(A)of Japan Society for the Promotion of Science(21H04535).
文摘The boundary lubrication mechanism at the articulating surface of natural synovial joints has been the subject of much discussion in tribology.In this study,to elucidate the lubricating function of the superficial area of articular cartilage and synovial fluid(SF),cartilage specimens were processed with four different treatments:gentle and severe washing with detergent,incubation in NaCl solution,and trypsin digestion to selectively remove certain constituents from the cartilage surface.Subsequently,the frictional characteristics were examined in phosphate-buffered saline(PBS)and SF against glass.Angularly reciprocating sliding tests with a spherical glass probe and square articular cartilage specimens were performed at low contact loads in the mN range to extract the frictional behavior in the superficial area of the cartilage specimens.Meanwhile,the cartilage surface was observed to confirm the effects of treatments on the morphology of the cartilage surface using a fluorescence microscope and water-immersion methods.The coefficient of friction(COF)of the prepared cartilage specimens was varied from 0.05 to over 0.3 in PBS.However,a certain group of cartilage specimens exhibited a low COF of less than 0.1 with limited variation.For the low COF group of specimens,all four treatments increased the COF in PBS to different extents,and fluorescence microscopy revealed that the integrity of the cartilage surface was deteriorated by treatments.This means that the intact cartilage surface had lubricating constituents to maintain low friction,and the removal of such constituents resulted in the loss of the intrinsic boundary lubricity of the cartilage surface.The variation in the COF of the cartilage specimens was suppressed in SF because it had a clear boundary lubrication effect on the cartilage surface.The lubricating effect of SF could be confirmed even after degenerative treatment.
基金supported by the National Key R&D Program of China (2019YFA0110600, China)Medical Research and Development Projects (BLB20J001, China)。
文摘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 intraarticular drug delivery systems(DDSs) in the future.
基金supported by the Areas of Excellence Scheme from University Grant Council of Hong Kong(AoE/M-402/20)the AO Foundation,Switzerland(AO-OCD Consortium TA1711481)+1 种基金the Theme-based Research Scheme from University Grant Council of Hong Kong(T13-402/17-N)the Mainland-Hong Kong Joint Funding Scheme of Innovation and Technology Fund:ITF MHKJFS(MHP/011/20).
文摘As a highly specialized shock-absorbing connective tissue,articular cartilage(AC)has very limited self-repair capacity after traumatic injuries,posing a heavy socioeconomic burden.Common clinical therapies for small-to medium-size focal AC defects are well-developed endogenous repair and cell-based strategies,including microfracture,mosaicplasty,autologous chondrocyte implantation(ACI),and matrix-induced ACI(MACI).However,these treatments frequently result in mechanically inferior fibrocartilage,low cost-effectiveness,donor site morbidity,and short-term durability.It prompts an urgent need for innovative approaches to pattern a pro-regenerative microenvironment and yield hyaline-like cartilage with similar biomechanical and biochemical properties as healthy native AC.Acellular regenerative biomaterials can create a favorable local environment for AC repair without causing relevant regulatory and scientific concerns from cell-based treatments.A deeper understanding of the mechanism of endogenous cartilage healing is furthering the(bio)design and application of these scaffolds.Currently,the utilization of regenerative biomaterials to magnify the repairing effect of joint-resident endogenous stem/progenitor cells(ESPCs)presents an evolving improvement for cartilage repair.This review starts by briefly summarizing the current understanding of endogenous AC repair and the vital roles of ESPCs and chemoattractants for cartilage regeneration.Then several intrinsic hurdles for regenerative biomaterials-based AC repair are discussed.The recent advances in novel(bio)design and application regarding regenerative biomaterials with favorable biochemical cues to provide an instructive extracellular microenvironment and to guide the ESPCs(e.g.adhesion,migration,proliferation,differentiation,matrix production,and remodeling)for cartilage repair are summarized.Finally,this review outlines the future directions of engineering the next-generation regenerative biomaterials toward ultimate clinical translation.
基金This work was supported by a grant from the National Natural Science Foundation of China (No. 81071203/H 1808).
文摘Background Quantitative T2 mapping has been a widely used method for the evaluation, of pathological cartilage properties, and the histological assessment system of osteoarthritis in the rabbit has been published recently. The aim of the study was to investigate the effectiveness of quantitative T2 mapping evaluation for articular cartilage lesions of a rabbit model of anterior cruciate liaament transection (ACLTI osteoarthritis.
基金the Grant-in-Aid for Specially Promoted Research of Japan Society for the Promotion of Science(23000011).
文摘The extremely low friction and minimal wear in natural synovial joints appear to be established by effective lubrication mechanisms based on appropriate combination of articular cartilage and synovial fluid.The complex structure of cartilage composed of collagen and proteoglycan with high water content contributes to high load-carrying capacity as biphasic materials and the various constituents of synovial fluid play important roles in various lubrication mechanisms.However,the detailed differences in functions of the intact and damaged cartilage tissues,and the interaction or synergistic action of synovia constituents with articular cartilage have not yet been clarified.In this study,to examine the roles of synovia constituents and the importance of cartilage surface conditions,the changes in friction were observed in the reciprocating tests of intact and damaged articular cartilage specimens against glass plate lubricated with lubricants containing phospholipid,protein and/or hyaluronic acid as main constituents in synovial fluid.The effectiveness of lubricant constituents and the influence of cartilage surface conditions on friction are discussed.In addition,the protectiveness by synovia constituents for intact articular cartilage surfaces is evaluated.
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.