1.Key roles of the superficial zone in articular cartilage physiology, pathology, and regeneration.
Li GUO ; Pengcui LI ; Xueqin RONG ; Xiaochun WEI
Chinese Medical Journal 2025;138(12):1399-1410
The superficial zone (SFZ) of articular cartilage is an important interface that isolates deeper zones from the microenvironment of the articular cavity and is directly exposed to various biological and mechanical stimuli. The SFZ is not only a crucial structure for maintaining the normal physiological function of articular cartilage but also the earliest site of osteoarthritis (OA) cartilage degeneration and a major site of cartilage progenitor cells, suggesting that the SFZ might represent a key target for the early diagnosis and treatment of OA. However, to date, SFZ research has not received sufficient attention, accounting for only about 0.58% of cartilage tissue research. The structure, biological composition, function, and related mechanisms of the SFZ in the physiological and pathological processes of articular cartilage remain unclear. This article reviews the key role of the SFZ in articular cartilage physiology and pathology and focuses on the characteristics of SFZ in articular cartilage degeneration and regeneration in OA, aiming to provide researchers with a systematic understanding of the current research status of the SFZ of articular cartilage, hoping that scholars will give more attention to the SFZ of articular cartilage in the future.
Cartilage, Articular/pathology*
;
Humans
;
Regeneration/physiology*
;
Animals
;
Osteoarthritis/physiopathology*
2.Finite element analysis of impact of bone mass and volume in low-density zone beneath tibial plateau on cartilage and meniscus in knee joint.
Longfei HAN ; Wenyuan HOU ; Shun LU ; Zijun ZENG ; Kun LIN ; Mingli HAN ; Guifeng LUO ; Long TIAN ; Fan YANG ; Mincong HE ; Qiushi WEI
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(3):296-306
OBJECTIVE:
To investigate the impact of bone mass and volume of low-density zones beneath the tibial plateau on the maximum von Mises stresses experienced by the cartilage and meniscus in the knee joint.
METHODS:
The study included one healthy adult volunteer, from whom CT scans were obtained, and one patient diagnosed with knee osteoarthrisis (KOA), for whom X-ray films were acquired. A static model of the knee joint featuring a low-density zone was established based on a normal knee model. In the finite element analysis, axial loads of 1 000 N and 1 800 N were applied to the weight-bearing region of the upper surface of the femoral head for model validation and subsequent finite element studies, respectively. The maximum von Mises stresses in the femoral cartilage, as well as the medial and lateral tibial cartilage and menisci, were observed, and the stress percentage of the medial and lateral components were concurrently analyzed. Additionally, HE staining, as well as alkaline magenta staining, were performed on the pathological specimens of patients with KOA in various low-density regions.
RESULTS:
The results of model validation indicated that the model was consistent with normal anatomical structures and correlated with previous calculations documented in the literature. Static analysis revealed that the maximum von Mises stress in the medial component of the normal knee was the lowest and increased with the advancement of the hypointensity zone. In contrast, the lateral component exhibited an opposing trend, with the maximum von Mises stress in the lateral component being the highest and decreasing as the hypointensity zone progressed. Additionally, the medial component experienced an increasing proportion of stress within the overall knee joint. HE staining demonstrated that the chondrocyte layer progressively deteriorated and may even disappear as the hypointensity zone expanded. Furthermore, alkaline magenta staining indicated that the severity of microfractures in the trabecular bone increased concurrently with the expansion of the hypointensity zone.
CONCLUSION
The presence of subtalar plateau low-density zone may aggravate joint degeneration. In clinical practice, it is necessary to pay attention to the changes in the subtalar plateau low-density zone and actively take effective measures to strengthen the bone status of the subtalar plateau low-density zone and restore the complete biomechanical function of the knee joint, in order to slow down or reverse the progression of osteoarthritis.
Humans
;
Finite Element Analysis
;
Knee Joint/physiology*
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Tibia/anatomy & histology*
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Cartilage, Articular/physiology*
;
Menisci, Tibial/physiopathology*
;
Tomography, X-Ray Computed
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Osteoarthritis, Knee/diagnostic imaging*
;
Weight-Bearing
;
Bone Density
;
Adult
;
Stress, Mechanical
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Male
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Middle Aged
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Biomechanical Phenomena
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Female
3.Experimental study on autologous osteochondral transplantation in the treatment of recurrent anterior dislocation of the shoulder joint with articular cartilage defect in rabbits.
Tao LIU ; Sen FANG ; Fang-Xiang LIU ; Ming-Tao ZHANG ; Zhi-Tao YANG ; Bo-Rong ZHANG ; Jun-Wen LIANG ; Xi-Hao WANG ; Jin JIANG ; Xiang-Dong YUN
China Journal of Orthopaedics and Traumatology 2025;38(6):619-625
OBJECTIVE:
To explore clinical effect of autologous osteochondral transplantation (AOT) in the treatment of recurrent anterior dislocation of the shoulder joint with glenoid cartilage defect in rabbits by establishing a model of recurrent anterior dislocation of the shoulder joint with < 20% glenoid cartilage defect in rabbits.
METHODS:
Twenty-four male New Zealand white rabbits, aged 6-month-old, weighed (2.69±0.17) kg were selected. The labrum of shoulder joint of rabbits was artificially destroyed to establish a model of recurrent anterior dislocation of shoulder joint with cartilage defect. They were divided into AOT surgery group and simple suture group, with 12 rabbits in each group. AOT group were underwent AOT surgery, while simple suture group was treated with simple Bankart suture for recurrent shoulder joint dislocation. At 6 and 12 weeks after operation, 6 rabbits between two groups were sacrificed for sampling. The dietary conditions, activity conditions, mental states of rabbits and healing conditions of grafts in the specimens were observed and compared between two groups. HE staining was used to observe cell creep, cell morphology, inflammatory cell infiltration, fibrochondrocytes and their arrangement. Masson staining was used to observe the formation and arrangement of collagen fibers; Safrane-green staining was used to observe the regeneration of articular cartilage, subchondral bone and bone tissue. Bone mineral density (BMD), bone volume (BV) and trabecular thickness (Tb.Th) between two groups were measured by Micro-CT to evaluate the remodeling of shoulder glenoid bone defects by autologous osteochondral cartilage.
RESULTS:
After different surgical interventions were carried out in both groups of rabbits, at 6 weeks after the operation, the abduction, extension, internal rotation and external rotation of the shoulder joint on the operated side showed limited range of motion compared with the contralateral side, while adduction and forward flexion showed no obvious abnormalities compared with the contralateral side. At 12 weeks after operation, the range motion of tshoulder joints in both groups of rabbits had returned to the state before modeling. The effects of HE staining, Masson staining and safrane-green staining at 12 weeks after operation in both groups were stronger than the staining results at 6 weeks after operation. Moreover, the results of HE staining, Masson staining and safranin fixation green staining in AOT group at 6 and 12 weeks after operation were all higher than those in simple suture group. Micro-CT scan results at 6 and 12 weeks after operation showed that BMD (0.427±0.014), (0.466±0.032) g·cm-3, BV(116.171±3.527), (159.327±3.500) mm3, and Tb.Th (0.230±0.006), (0.285±0.009) mm in AOT group, which were higher than those of simple suture group in BMD(0.358±0.011), (0.384±0.096) g·cm-3, BV(72.657±3.903), (118.713±3.860) mm3, and Tb.Th(0.204±0.009), (0.243±0.007) mm;and the differences were statistically significant (P<0.05).
CONCLUSION
AOT procedure could effectively promote osteogenesis and fibrocartilage regeneration in the cartilage defect area of the shoulder glenoid <20%, which is conducive to reshaping the structure of the shoulder glenoid.
Animals
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Rabbits
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Male
;
Transplantation, Autologous
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Cartilage, Articular/injuries*
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Shoulder Dislocation/physiopathology*
;
Bone Transplantation
;
Shoulder Joint/surgery*
4.Finite element analysis of the correlation between lateral collateral ligament injury of the ankle joint and subtalar articular cartilage injury.
Hai-Yang ZHANG ; Bo LOU ; Zheng LIU ; Zhe ZHU ; Huan WANG
China Journal of Orthopaedics and Traumatology 2025;38(6):626-632
OBJECTIVE:
To establish foot and ankle models of different lateral collateral ligament injuries of ankle joint, and conduct finite element analysis on, and to explore the force conditions of subtalar articular cartilage during foot inversion movements under different gait stages and under different loads.
METHODS:
A normal ankle CT scan of a 30-year-old male healthy volunteer (heighted 175 cm and weighted 60 kg) was selected. The CT images were imported into software such as Mimics 21.0, Geomajic 2017, and Solidworks 2017 respectively, extract the normal ankle bone model. Then, the foot and ankle finite element models of different lateral collateral ligament injuries of ankle joint were constructed and divided into anterior talofibular ligament(ATFL) rupture group, ATFL and calcaneo fibular ligament (CFL) rupture group, ATFL, CFL and posterior talofibular ligament (PTFL) rupture group, and control group with intact ligament function by ANSYS 2021. Corresponding horizontal and vertical loads and torques were applied respectively on tibia and talus according to the force conditions of different phases to simulate landing phase, neutral and off-ground phase in walking gait. The changes in stress distribution area and stress peak of subtalar articular cartilage in the loading phase, neutral phase and off-ground phase gaits among four groups were observed. Simulate varus sprain action, apply different loads of 600, 1, 800, and 4, 200 N respectively, and changes in stress distribution area and the stress peak of subtalar articular cartilage among four groups of models were observed.
RESULTS:
In the gait simulation, the stress results of loading phase in ATFL fracture group, ATFL and CFL fracture groups, ATFL, CFL and PTFL fracture groups, and control group were 0.889 54, 0.960 89, 1.139 20, and 0.722 64 MPa, respectively. The neutral response force results were 1.250 60, 1.358 50, 1.363 70, 1.246 40 MPa respectively;the results of corresponding forces off-ground phase were 1.029 90, 1.138 70, 1.145 90 and 0.832 40 MPa respectively. In the inversion simulation, the stresses of ATFL fracture group, ATFL and CFL fracture groups, ATFL, CFL and PTFL fracture groups, and control group under load of 600 N were 2.191 3, 2.208 5, 2.215 7, and 2.156 6 MPa respectively. The stresses under a load of 1 800 N were 7.134 7, 9.715 2, 10.064 0, and 7.107 0 MPa respectively;the stresses under a load of 4 200 N were 17.435 0, 25.309 0, 26.119 0 and 16.010 0 MPa respectively.
CONCLUSION
The lateral collateral ligament of ankle joint plays an important role in the stability of the subtalar joint, especially CFL plays an important role in restricting calcaneal varus. If these ligaments are damaged, it will cause instability of the subtalar joint and further lead to lesions in the subtalar articular cartilage. Relevant exercises should be reduced or the ligament injuries should be treated in a timely manner.
Humans
;
Finite Element Analysis
;
Male
;
Adult
;
Cartilage, Articular/physiopathology*
;
Ankle Injuries/physiopathology*
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Ankle Joint/physiopathology*
;
Biomechanical Phenomena
;
Subtalar Joint/injuries*
;
Tomography, X-Ray Computed
5.One-year recovery after lateral retinaculum release combined with chondroplasty in patients with lateral patellar compression syndrome.
Zhen-Long LIU ; Yi-Ting WANG ; Jin-Ming LIN ; Wu-Ji ZHANG ; Jiong-Yuan LI ; Zhi-Hui HE ; Yue-Yang HOU ; Jian-Li GAO ; Wei-Li SHI ; Yu-Ping YANG
Chinese Journal of Traumatology 2025;28(6):462-468
PURPOSE:
Lateral patellar compression syndrome (LPCS) is characterized by a persistent abnormally high stress exerted on the lateral articular surface of the patella due to lateral patellar tilt without dislocation and lateral retinaculum contracture, leading to anterior knee pain. The purpose of this study is to evaluate the efficacy and prognosis of lateral retinaculum release (LRR) combined with chondroplasty in the treatment of LPCS.
METHODS:
This retrospective study evaluated 40 patients who underwent LRR combined with chondroplasty for LPCS between 2020 and 2021. The assessment included improvement in postoperative tenderness and knee joint function. Patients were evaluated using the Lysholm, Tegner, and International Knee Documentation Committee 2000 scoring systems, as well as the visual analog scale, both preoperatively and postoperatively, with the paired comparisons analyzed using a t-test. Additionally, intraoperative observations were made regarding knee joint lesions, including cartilage damage and osteophyte formation, with analysis by the Chi-square test.
RESULTS:
The visual analog scale score for tenderness showed a significant decrease after surgery (p < 0.001). Evaluation of knee joint function also indicated significant improvements, as demonstrated by increased Lysholm, Tegner, and International Knee Documentation Committee 2000 scores postoperatively (p < 0.001, p = 0.011, p < 0.001, respectively). Furthermore, all LPCS patients included in the study presented with cartilage injuries and osteophyte formation. Significant differences were noted in the incidence of cartilage damage and osteophyte formation at different locations within the knee among patients with LPCS.
CONCLUSION
LRR combined with chondroplasty is an effective surgical approach for treating patients with LPCS, with satisfactory recovery observed at the 1-year follow-up. Additionally, the incidence of cartilage damage and osteophyte formation in LPCS patients varies significantly depending on the specific location within the knee joint.
Humans
;
Male
;
Female
;
Retrospective Studies
;
Adult
;
Middle Aged
;
Patella/surgery*
;
Knee Joint/physiopathology*
;
Recovery of Function
;
Young Adult
;
Treatment Outcome
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Cartilage, Articular/surgery*
;
Adolescent
6.Increased Chondrocyte Apoptosis in Kashin-Beck Disease and Rats Induced by T-2 Toxin and Selenium Deficiency.
Hao Jie YANG ; Ying ZHANG ; Zhi Lun WANG ; Sen Hai XUE ; Si Yuan LI ; Xiao Rong ZHOU ; Meng ZHANG ; Qian FANG ; Wen Jun WANG ; Chen CHEN ; Xiang Hua DENG ; Jing Hong CHEN
Biomedical and Environmental Sciences 2017;30(5):351-362
OBJECTIVETo investigate chondrocyte apoptosis and the expression of biochemical markers associated with apoptosis in Kashin-Beck disease (KBD) and in an established T-2 toxin- and selenium (Se) deficiency-induced rat model.
METHODSCartilages were collected from the hand phalanges of five patients with KBD and five healthy children. Sprague-Dawley rats were administered a selenium-deficient diet for 4 weeks prior to T-2 toxin exposure. The apoptotic chondrocytes were observed by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Caspase-3, p53, Bcl-2, and Bax proteins in the cartilages were visualized by immunohistochemistry, their protein levels were determined by Western blotting, and mRNA levels were determined by real-time reverse transcription polymerase chain reaction.
RESULTSIncreased chondrocyte apoptosis was observed in the cartilages of children with KBD. Increased apoptotic and caspase-3-stained cells were observed in the cartilages of rats fed with normal and Se-deficient diets plus T-2 toxin exposure compared to those in rats fed with normal and Se-deficient diets. Caspase-3, p53, and Bax proteins and mRNA levels were higher, whereas Bcl-2 levels were lower in rats fed with normal or Se-deficiency diets supplemented with T-2 toxin than the corresponding levels in rats fed with normal diet.
CONCLUSIONT-2 toxin under a selenium-deficient nutritional status induces chondrocyte death, which emphasizes the role of chondrocyte apoptosis in cartilage damage and progression of KBD.
Adolescent ; Animals ; Apoptosis ; drug effects ; Biomarkers ; Cartilage, Articular ; physiopathology ; Child ; Chondrocytes ; physiology ; Female ; Humans ; Kashin-Beck Disease ; etiology ; physiopathology ; Male ; Matrilin Proteins ; genetics ; metabolism ; Models, Animal ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Selenium ; deficiency ; T-2 Toxin ; pharmacology
7.Effect of eletroacupuncture with close-to-bone needling treatment on expression of Sox9, VEGF and ColX in impaired cartilage of rabbits with knee osteoarthritis.
Fei LIU ; Xue-Zhi LI ; Ni-Ni FU ; Xiao-Fang XI ; Yi REN ; Xiao-Guang YANG ; Yu ZHANG
Journal of Southern Medical University 2016;36(7):997-1003
OBJECTIVETo investigate the effect of eletroacupuncture with close-to-bone needling treatment on expression of Sox9, vascular endothelial growth factor (VEGF) and type X collagen (ColX) in impaired cartilage of rabbits with knee osteoarthritis (KOA) and explore its possible mechanisms.
METHODSForty New Zealand rabbits were randomized equally into normal control group, KOA model group, eletroacupuncture with close-to-bone needling group (CN group), and normal thrust needing group (NTN group). In the latter 3 groups, KOA was induced by Hulth-Telhag treatment and evaluated with X-ray examination, and 6 weeks after the modeling, eletroacupuncture for 20 min was administered in CN and NTN groups at the acupoints "Zusanli", "Waixiyan", "Neixiyan", "Liangqiu" and "Yinlingquan" in the left knee joints once daily for 5 days as a treatment cycle. After 5 treatment cycles, the rabbits were examined for behavioral changes, cartilage morphology, and Mankin scores; The protein and mRNA expressions of S0x9, VEGF, and ColX were examined using Westen blotting, immunohistochemistry, and RT-PCR as appropriate.
RESULTSThe rabbits in the model, CN and NTN groups showed significant changes in behaviors and cartilage histomorphology after the modeling and after the treatments. HE staining showed that cartilage injury was repaired and tended to recovery in CN and NTN groups. The cartilage pathologies was severer in the model group than in the normal control, CN and NTN groups (P<0.01); Sox9 protein increased and VEGF mRNA level decreased in CN and NTN groups after treatment as compared with those in the model group (P<0.01).
CONCLUSIONEletroacupuncture with close-to-bone needling can effectively improve KOA in rabbits probably by enhancing Sox9 and reducing VEGF and ColX expressions in the cartilage to inhibit hypertrophic differentiation of the chondrocytes, maintain chondrogenic phenotype and repair cartilage cells.
Acupuncture Points ; Animals ; Cartilage, Articular ; metabolism ; pathology ; Cell Differentiation ; Chondrocytes ; cytology ; Chondrogenesis ; Collagen Type X ; metabolism ; Electroacupuncture ; Knee Joint ; physiopathology ; Osteoarthritis, Knee ; therapy ; Rabbits ; SOX9 Transcription Factor ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism
8.The value of 3 dimensional-fat suppression-spoiled gradient-recalled acquisition sequence on single compartment osteoarthritis for unicompartmental arthroplasty preoperative assessment.
Gang ZHAO ; Yujie LIU ; Email: LIUYUJIE301@163.COM. ; Feng QU ; Bangtuo YUAN ; Jiangtao WANG ; Xuezhen SHEN ; Hongliang LI ; Xi LU ; Qi GUO ; Wei QI ; Yang LIU ; Juanli ZHU
Chinese Journal of Surgery 2015;53(7):528-532
OBJECTIVETo analyze the 3 dimensional-fat suppression-spoiled gradient-recalled acquisition (3D-FS-SPGR) sequence in the diagnosis of knee articular cartilage injury.
METHODSA total of 56 knee osteoarthritis patients (26 males, 30 females, ages 52-73 years, mean 61.8 years) treated in Department of Orthopedics, Chinese People's Liberation Army General Hospital between June 2013 and May 2014 were involved in this study. All patients underwent knee MRI, plus 3D-FS-SPGR sequence, arthroscopic exploration, and in contrast to the results of MRI results analysis, evaluation 3D-FS-SPGR and conventional sequence of cartilage damage consistent with the arthroscopic accuracy.
RESULTSDivided 56 knee joints into 336 cartilage articular surface, included 55.1% normal articular surface, 21.4% early osteoarthritis and 23.5% advanced osteoarthritis. The accordance of 3D-FS-SPGR sequence grading and arthroscopic was 90.2%. The sensitivity of 3D-FS-SPGR sequence was 93.1%, specificity was 98.3%, and Kappa value was 0.849. The sensitivity of T2WI sequence was 84.4%, specificity was 96.9%, and the Kappa value was 0.671.
CONCLUSIONFor unicompartment osteoarthritis , MRI 3D-FS-SPGR sequence is effective in sensitivity and specificity of cartilage damage.
Aged ; Arthroplasty ; Arthroscopy ; Cartilage, Articular ; Female ; Humans ; Knee Injuries ; diagnosis ; Knee Joint ; physiopathology ; surgery ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Orthopedic Procedures ; Osteoarthritis, Knee ; surgery ; Preoperative Care ; Sensitivity and Specificity
9.Quantitative T2 mapping evaluation for articular cartilage lesions in a rabbit model of anterior cruciate ligament transection osteoarthritis.
Zheng-mao WEI ; Xiang-ke DU ; Tian-long HUO ; Xu-bin LI ; Guang-nan QUAN ; Tian-ran LI ; Jin CHENG ; Wei-tao ZHANG
Chinese Medical Journal 2012;125(5):843-850
BACKGROUNDQuantitative 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 ligament transection (ACLT) osteoarthritis.
METHODSTwenty New Zealand White (NZW) rabbits were divided into ACLT surgical group and sham operated group equally. The anterior cruciate ligaments of the rabbits in ACLT group were transected, while the joints were closed intactly in sham operated group. Magnetic resonance (MR) examinations were performed on 3.0T MR unit at week 0, week 6, and week 12. T2 values were computed on GE ADW4.3 workstation. All rabbits were killed at week 13, and left knees were stained with Haematoxylin and Eosin. Semiquantitative histological grading was obtained according to the osteoarthritis cartilage histopathology assessment system. Computerized image analysis was performed to quantitate the immunostained collagen type II.
RESULTSThe average MR T2 value of whole left knee cartilage in ACLT surgical group ((29.05±12.01) ms) was significantly higher than that in sham operated group ((24.52±7.97) ms) (P=0.024) at week 6. The average T2 value increased to (32.18±12.79) ms in ACLT group at week 12, but remained near the baseline level ((27.66±8.08) ms) in the sham operated group (P=0.03). The cartilage lesion level of left knee in ACLT group was significantly increased at week 6 (P=0.005) and week 12 (P<0.001). T2 values had positive correlation with histological grading scores, but inverse correlation with optical densities (OD) of type II collagen.
CONCLUSIONThis study demonstrated the reliability and practicability of quantitative T2 mapping for the cartilage injury of rabbit ACLT osteoarthritis model.
Animals ; Anterior Cruciate Ligament ; metabolism ; physiopathology ; Cartilage, Articular ; metabolism ; physiopathology ; Collagen Type II ; metabolism ; Magnetic Resonance Imaging ; Male ; Osteoarthritis ; metabolism ; physiopathology ; Rabbits
10.Research of repairing rabbit knee joint cartilage defect by compound material of fibrin glue and decalcified bone matrix (DBM) and chondrocytes.
Jie HE ; Xiang YANG ; Peng-ju YUE ; Guan-yu WANG ; Ting GUO ; Jian-ning ZHAO
China Journal of Orthopaedics and Traumatology 2009;22(7):523-526
OBJECTIVETo investigate the feasibility and effectivity of using compound material of fibrin glue and DBM as scaffolds for cartilage tissue engineering.
METHODSChondrocytes isolated from articular cartilage were seeded into prepared scaffolds, after incubation for 4 weeks in vitro. Chondrocytes and fibrin glue and DBM constructs were implanted in the joint cave of rabbit. The specimens were excised at the 4th, 8th, 12th week, examined grossly analyzed by haematoxylin cosine, toluidine blues staining and type II collagen immunohistochemistry reaction. Wakitani score was counted to evaluate the repairing effect.
RESULTSGrossly analysis showed some ivory tissue filled the caves after 4 weeks and the caves were full filled with smooth surface after 12 weeks. The microscope showed a good deal of chondrocytes appeared after 8 weeks and more type II collagen than 4 weeks. Twelve weeks later, cartilage lacuna could be observed. The cells arrangement and the amount of type II collagen both showed the same as the natural one.
CONCLUSIONComplicated material of fibrin glue and DBM as scaffolds can be used as scaffolds for cartilage tissue engineering.
Animals ; Bone Matrix ; physiology ; transplantation ; Cartilage, Articular ; physiopathology ; surgery ; Cell Transplantation ; Cells, Cultured ; Chondrocytes ; physiology ; transplantation ; Female ; Fibrin Tissue Adhesive ; therapeutic use ; Male ; Rabbits ; Random Allocation ; Regeneration ; Tissue Adhesives ; therapeutic use ; Tissue Engineering ; Tissue Scaffolds

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