RESUMEN
To demonstrate the current strategies for treating cartilage defects of knees and the related research. Published papers about cartilage defects were searched and reviewed. The current strategies for the treatment were summarized. Based on the research of our study and others, the conclusion how to treat cartilage defects was made. The current ways for treating cartilage defects include micro-fractures, chondrocytes transplantation, mosaicplasty and tissue engineering; Research on functional magnetic resonance imaging in the early diagnosis of cartilage defects, cartilage degeneration is gradually increasing. There is still no effective treatment of cartilage defects and tissue engineering has brought new hopes for the treatment of cartilage defects , functional magnetic resonance imaging has some significance in early diagnosis of cartilage defects, cartilage degeneration.
Asunto(s)
Enfermedades de los Cartílagos/terapia , Rodilla/cirugía , Animales , Enfermedades de los Cartílagos/cirugía , Cartílago Articular/cirugía , Humanos , Ingeniería de Tejidos , Trasplante AutólogoRESUMEN
The aim of this study was to assess the feasibility of creating extracellular matrix (ECM) scaffolds from mesenchymal stem cells. Bone marrow mesenchymal stem cell (BMSC)-derived ECM (BMSC-dECM) scaffolds were fabricated by lyophilization after crosslinking, without using a decellularization process. Acellular porcine chondrocyte-derived ECM (AC-dECM) scaffolds were used as a control. The surface morphology, internal structure, water uptake ratio, mechanical properties, and biocompatibility of the scaffolds, as well as the in vitro behavior of cells grown on the scaffolds were examined and compared between the two scaffold types. For the BMSC-dECM scaffolds, the average pore size was 304.4 ± 108.2 µm, average porosity was 93.3% ± 4.5%, average compressive modulus was 6.8 ± 1.5 kPa, and average water uptake ratio exceeded 20. The BMSC-dECM scaffolds supported the in vitro attachment and proliferation of cells, with these aspects likely being comparable to those of the AC-dECM scaffolds. The findings of this preliminary study highlight the potential utility of BMSC-derived ECM scaffolds for future cartilage tissue-engineering applications.
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Materiales Biocompatibles , Células de la Médula Ósea/ultraestructura , Matriz Extracelular/ultraestructura , Células Madre Mesenquimatosas/ultraestructura , Andamios del Tejido , Adipogénesis , Animales , Células de la Médula Ósea/citología , Adhesión Celular , División Celular , Células Cultivadas , Condrocitos/citología , Condrogénesis , Fuerza Compresiva , Reactivos de Enlaces Cruzados , Estudios de Factibilidad , Liofilización , Interacciones Hidrofóbicas e Hidrofílicas , Microscopía Electrónica , Microscopía Electrónica de Rastreo , Osteogénesis , Porosidad , ConejosRESUMEN
Cartilage tissue engineering using cells and biocompatible scaffolds has emerged as a promising approach to repair of cartilage damage. To date, however, no engineered cartilage has proven to be equivalent to native cartilage in terms of biochemical and compression properties, as well as histological features. An alternative strategy for cartilage engineering is to focus on the in vivo regeneration potential of immature engineered cartilage. Here, we used a rabbit model to evaluate the extent to which the maturity of engineered cartilage influenced the remodeling and integration of implanted extracellular matrix scaffolds containing allogenous chondrocytes. Full-thickness osteochondral defects were created in the trochlear groove of New Zealand white rabbits. Left knee defects were left untreated as a control (group 1), and right knee defects were implanted with tissue-engineered cartilage cultured in vitro for 2 days (group 2), 2 weeks (group 3), or 4 weeks (group 4). Histological, chemical, and compression assays of engineered cartilage in vitro showed that biochemical composition became more cartilagenous, and biomechanical property for compression gradually increased with culture time. In an in vivo study, gross imaging and histological observation at 1 and 3 months after implanting in vitro-cultured engineered cartilage showed that defects in groups 3 and 4 were repaired with hyaline cartilage-like tissue, whereas defects were only partially filled with fibrocartilage after 1 month in groups 1 and 2. At 3 months, group 4 showed striking features of hyaline cartilage tissue, with a mature matrix and a columnar arrangement of chondrocytes. Zonal distribution of type II collagen was most prominent, and the International Cartilage Repair Society score was also highest at this time. In addition, the subchondral bone was well ossified. In conclusion, in vivo engineered cartilage was remodeled when implanted; however, its extent to maturity varied with cultivation period. Our results showed that the more matured the engineered cartilage was, the better repaired the osteochondral defect was, highlighting the importance of the in vitro cultivation period.
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Huesos/patología , Cartílago Articular/patología , Ingeniería de Tejidos/métodos , Cicatrización de Heridas , Animales , Colágeno/metabolismo , Colágeno Tipo II/metabolismo , Fuerza Compresiva , ADN/metabolismo , Matriz Extracelular/metabolismo , Glicosaminoglicanos/metabolismo , Inmunohistoquímica , Implantes Experimentales , Ensayo de Materiales , Conejos , Coloración y Etiquetado , Sus scrofaRESUMEN
BACKGROUND: The authors devised a double-bundle posterior cruciate ligament reconstruction technique in combination with a single-sling method. However, the double-bundle technique needs more simplicity and a decreased possibility of failure. HYPOTHESIS: A novel surgical technique of transtibial double-bundle posterior cruciate ligament reconstruction using a single-sling method with a tibialis anterior allograft, previously introduced, produces satisfactory results. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Twenty-one patients who underwent double-bundle transtibial isolated posterior cruciate ligament reconstruction using a single-sling method between July 2003 and September 2007 were enrolled in this study. The exclusion criteria applied were (1) a multiligamentous injury, (2) posterior cruciate ligament reconstruction previously performed using another technique, and (3) the presence of any additional injury capable of affecting knee stability. The Lysholm and International Knee Documentation Committee (IKDC) knee scales were used for the clinical outcome evaluation. Stability was evaluated using a KT-2000 arthrometer. The evaluation was performed by comparing preoperative and last follow-up results. RESULTS: Nineteen men and 2 women were enrolled, with a mean follow-up of 49.2 months (range, 25-73 months). The mean Lysholm score was 53 ± 5.3 (range, 34-68) preoperatively and improved to 83.5 ± 13 (range, 61-97) at the last follow-up after surgery (P < .001). The IKDC score also improved from preoperative (0 A, 0 B, 7 C, 14 D) to final follow-up (8 A, 9 B, 3 C, 1 D; P < .001). Mean side-to-side difference in posterior translation, measured using the KT-2000 arthrometer, was 13.5 ± 1.2 mm preoperatively and 3.4 ± 0.8 mm at last follow-up evaluations (mean 51.7 months postoperatively). CONCLUSION: After follow-up for longer than 24 months, the transtibial double-bundle posterior cruciate ligament reconstruction with a single sling was found to produce satisfactory clinical and stability results, which indicates that the described technique should be viewed as a viable alternative.
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Procedimientos de Cirugía Plástica/métodos , Ligamento Cruzado Posterior/cirugía , Tendones/trasplante , Trasplante Homólogo , Adolescente , Adulto , Artroscopía/métodos , Femenino , Estudios de Seguimiento , Humanos , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
A cell-derived extracellular matrix (ECM) scaffold was constructed using cultured porcine chondrocytes via a freeze-drying method, and its ability to promote cartilage formation was evaluated in vitro. Scanning electron microscope (SEM) revealed that the scaffold had highly uniform porous microstructure. Then, rabbit chondrocytes were seeded dynamically on ECM scaffold and cultured for 2 days, 1, 2, and 4 weeks in vitro for analysis. Polyglycolic acid (PGA) scaffold was used as a control. On gross observation of neocartilage tissue, a silvery white cartilage-like tissue was observed after 1 week of culture in ECM scaffold, while similar morphology was seen only after 4 weeks in PGA scaffold. The volume of neocartilage-like tissue was significantly increased in both ECM and PGA groups. The compressive strength was gradually increased with time in ECM group, while gradually decreased in PGA group. DNA, glycosaminoglycan (GAG) and collagen contents also increased gradually with time in both groups, but showed more significant increase in ECM group. Histological staining for GAG (Safranin O staining) and type II collagen (immunohistochemistry) showed sustained accumulation of ECM molecules with time, which gradually and uniformly filled porous space in ECM scaffold. On the contrary, they accumulated only at the peripheral area of PGA scaffold. These results suggest that a novel cell-derived ECM scaffold can provide a promising environment for generating a high quality cartilage in vitro.
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Cartílago , Matriz Extracelular/química , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Animales , Materiales Biocompatibles/química , Cartílago/citología , Cartílago/metabolismo , Forma de la Célula , Células Cultivadas , Condrocitos/citología , Condrocitos/metabolismo , Colágeno Tipo II/metabolismo , Fuerza Compresiva , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Porosidad , Proteoglicanos/química , Conejos , Estrés Mecánico , Porcinos , Ingeniería de Tejidos/instrumentaciónRESUMEN
We designed chiral 2-nitroimidazole derivatives containing a 2-aminomethylene-4-cyclopentene-1,3-dione moiety as antiangiogenic hypoxic cell radiosensitizers. Based on results of molecular orbital calculations, the 2-aminomethylene-4-cyclopentene-1,3-dione moiety is expected to show high electrophilicity comparable to that of the 2-methylene-4-cyclopentene-1,3-dione moiety included in TX-1123 and tyrphostin AG17. We evaluated the antiangiogenic and radiosensitizing effects of the new compounds, along with other biological properties including their activities as hypoxic cytotoxicities and protein tyrosine kinase (PTK) inhibitory activities. Among the compounds tested, 5 (TX-2036) proved to be the strongest antiangiogenic hypoxic cell radiosensitizer. All the other chiral 2-nitroimidazole derivatives having 2-aminomethylene-4-cyclopentene-1,3-dione moiety tested were also antiangiogenic hypoxic cell radiosensitizers. The PTK inhibitory activity of 5 (TX-2036) showed this to be a promising and potent EGFR kinase inhibitor, having an IC(50) value of lower than 2microM. This compound also was an Flt-1 kinase inhibitor having an IC(50) value of lower than 20microM. Our results show that these chiral 2-nitroimidazole derivatives that contain the 2-aminomethylene-4-cyclopentene-1,3-dione moiety as a potent antiangiogenic pharmacophoric descriptor are promising lead candidates for the development of antiangiogenic hypoxic cell radiosensitizers.
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Inhibidores de la Angiogénesis/síntesis química , Hipoxia de la Célula/efectos de los fármacos , Ciclopentanos/síntesis química , Diseño de Fármacos , Nitroimidazoles/química , Fármacos Sensibilizantes a Radiaciones/síntesis química , Inhibidores de la Angiogénesis/toxicidad , Animales , Antineoplásicos/síntesis química , Antineoplásicos/toxicidad , Línea Celular , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Embrión de Pollo , Ciclopentanos/toxicidad , Ratones , Modelos Moleculares , Nitroimidazoles/toxicidad , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/toxicidad , Fármacos Sensibilizantes a Radiaciones/toxicidad , Ratas , EstereoisomerismoRESUMEN
Reconstruction of the posterior cruciate ligament (PCL) has been performed in various ways. Recent biomechanical tests revealed that a double-bundle graft with a 2-tunnel technique is more likely to restore normal knee stability throughout the full range of knee motion. Several techniques using double-bundle grafts have been implemented for PCL reconstruction; however, each technique has its own advantages and disadvantages. To provide a simplified surgical technique and minimize its inherent complications, the purpose of this study was to introduce a novel technique of arthroscopic PCL reconstruction using an allogeneic tibialis anterior tendon and forming a single sling.
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Artroscopía/métodos , Ligamento Cruzado Posterior/cirugía , Tendones/trasplante , Humanos , Trasplante de Órganos/métodosRESUMEN
We have observed in our previous study that a cell-derived extracellular matrix (ECM) scaffold could assure the growth of a cartilage tissue construct in vitro. The purpose of the present study was to evaluate the feasibility of a chondrocyte-seeded cell-derived ECM scaffold by implanting it in vivo in nude mouse. A porous cell-derived ECM scaffold was prepared with a freeze-drying protocol using porcine chondrocytes. Rabbit articular chondrocytes were seeded onto the scaffold and cultured for 2 days in vitro, and then implanted into the nude mouse subcutaneously. They were retrieved at 1, 2, and 3 weeks postimplantation. Under macroscopic analysis, the cartilage-like tissue formation matured with time and developed a smooth, white surface. Contrary to the control (in which no cells were seeded), the size of the neocartilage tissue increased slightly by the third week and remained more stable. Total glycosaminoglycan (GAG) content and the GAG/DNA ratio increased significantly with time in the chemical analysis. The histology exhibited a sustained accumulation of newly synthesized sulfated proteoglycans. Immunohistochemistry, Western blot, and reverse transcriptase-polymerase chain reaction (RT-PCR) clearly identified type II collagen at all time points. Compressive strength of in vivo neocartilage increased from 0.45 +/- 0.06 MPa at 1 week to 1.18 +/- 0.17 MPa at 3 weeks. In conclusion, this study demonstrated that the cell-derived ECM scaffold could provide chondrocytes with favorable in vivo environment to produce a hyaline-like cartilage tissue.
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Materiales Biocompatibles , Cartílago/metabolismo , Condrocitos/trasplante , Colágeno Tipo II/metabolismo , Matriz Extracelular/fisiología , Ingeniería de Tejidos/métodos , Animales , Condrocitos/fisiología , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo II/genética , Histocitoquímica , Ratones , Ratones Desnudos , Microscopía Electrónica de Rastreo , Modelos Animales , Conejos , PorcinosRESUMEN
The purpose of this study is to evaluate the feasibility of human amniotic membrane (HAM) as a chondrocyte carrier by assessing cell proliferation and maintenance of phenotype in vitro and cartilage regeneration in vivo. Intact HAM was treated with 0.1% trypsin-ethylenediaminetetraacetic acid (EDTA) for 15 min and the epithelial cells removed to make a denuded HAM. Rabbit articular chondrocytes were then seeded on three different HAM substrates: the epithelial side of intact HAM (IHE), basement side of denuded HAM (DHB), and stromal side of denuded HAM (DHS). These cell-substrate specimens were cultured for up to 4 weeks, and cell proliferation rate and phenotypic stability were examined at weeks 1 and 4. While chondrocytes grew in monolayer fashion on the surface of IHE and DHB substrates, the cells seeded in DHS penetrated and spread into the whole thickness of the stromal layer. The proliferating activity of chondrocytes in DHB was continuously up-regulated. A similar proliferating activity was observed in DHS in the first week, which remained stable for up to 4 weeks. The expression of type II collagen gradually increased with time in the DHS group, while it gradually decreased in the DHB group or was not detected at all in the IHE group. These results suggested that denuded HAM was able to support chondrocyte proliferation and maintenance of phenotype in vitro, seemingly more favorable when DHS was used. Based on this data, the DHS with chondrocytes was used to cover rabbit osteochondral defect with the stromal side facing in. The defect area was successfully regenerated with hyaline cartilage in the Safranin-O stain and International Cartilage Repair Society (ICRS) scoring after 8 weeks of implantation. In conclusion, our findings suggest that denuded HAM could be one of the ideal cell carrier matrices for cartilage regeneration.
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Amnios/trasplante , Cartílago Articular/crecimiento & desarrollo , Cartílago Articular/cirugía , Condrocitos/citología , Condrocitos/trasplante , Fracturas del Cartílago/cirugía , Ingeniería de Tejidos/métodos , Amnios/patología , Animales , Cartílago Articular/patología , Técnicas de Cultivo de Célula/métodos , Células Cultivadas , Fracturas del Cartílago/patología , Conejos , Resultado del TratamientoRESUMEN
BACKGROUND: A clavicle fracture is a common traumatic injury. However, the high percentage of distal clavicle fractures associated with a rupture of the coracoclavicular (CC) ligament can result in delayed union or nonunion. There is no standard treatment for a clavicle fracture. This report introduces a method for treating distal clavicle fractures associated with a ruptured CC ligament using a cannulated screw. METHODS: Seventeen patients suffering from a clavicle fracture caused by a rupture of the CC ligament were treated with a closed reduction and a cannulated screw fixation technique. Twelve patients were male and five were female and the average age was 30.5 years (range, 8-64 years). The patients were assessed using a clinical and radiologic evaluation as well as by the University of California at Los Angeles (UCLA) shoulder rating scale for 12 to 16 months after surgery. RESULTS: After confirming the formation of a callus, the implants were routinely removed approximately 8 weeks after surgery in all patients except for one. In this patient, the implant was removed 16 weeks after surgery as a result of a loosened screw, which caused displacement at the fracture site. During the final follow-up, the fracture site displayed nonunion and a partially limited range of motion (ROM). The shoulder function of the other 16 patients was restored to the preinjury level after 4 approximately 6 months of treatment. In one patient, heterotopic ossification was observed along the CC ligament without any functional deficit. All but one patient showed good results according to the UCLA scale. CONCLUSIONS: The cannulated screw fixation technique can maintain the rigid fixation of fracture fragments and allow an early return to work and sport activities. Therefore, the cannulated screw fixation technique is expected to be a useful method for treating distal clavicle fractures associated with a coracoclavicular ligament rupture.
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Tornillos Óseos , Clavícula/lesiones , Fijación Interna de Fracturas/métodos , Fracturas Óseas/cirugía , Ligamentos/lesiones , Adolescente , Adulto , Niño , Femenino , Curación de Fractura , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/etiología , Fracturas Óseas/rehabilitación , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Rango del Movimiento Articular , Rotura , Articulación del HombroRESUMEN
High molecular weight (MW) hyaluronan (HA) preparation is considered to be more biologically active than HAs of lower MWs. However, many of the HA preparations currently used to treat osteoarthritis (OA) have lower MWs by the enhanced penetration of HA molecules into the synovial lining cells. In this study, we determined the effectiveness of sonophoresis on the delivery of high MW HA into synovial membrane using an animal model of OA. A total of 1000 kDa (HA1000) and 3000 kDa (HA3000) HA were labeled with fluorescein and injected into the knees of rabbits. Low-intensity continuous ultrasound at 1 MHz, 400 mW/cm2 was applied to the knees for 10 min treatment bid. Synovial fluid analysis revealed increased absorption and fluorescence microscopy showed deeper penetration of both HA1000 and HA3000, more so with the latter. Histologic examination indicated that ultrasound treatment resulted in no apparent damage to the synovial membrane. These results suggest that simultaneous sonication with HA injection might compensate for the short half-life of HA. Consequently, this dual treatment would render HA a far more effective tool in the management of OA.
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Ácido Hialurónico/administración & dosificación , Osteoartritis de la Rodilla/terapia , Sonicación , Membrana Sinovial/metabolismo , Animales , Femenino , Semivida , Miembro Posterior , Ácido Hialurónico/química , Ácido Hialurónico/metabolismo , Modelos Animales , Peso Molecular , Osteoartritis de la Rodilla/metabolismo , Osteoartritis de la Rodilla/patología , Conejos , Líquido Sinovial/química , Líquido Sinovial/metabolismo , Membrana Sinovial/patologíaRESUMEN
(R)- and (S)-Epichlorohydrins were used to prepare the enantiomers of sterically diverse haloacetylcarbamoyl-2-nitroimidazoles that function as hypoxic cell radiosensitizers. The synthetic design allowed for introduction of a side chain of varying bulk that permitted an examination of the steric effects on enantio-discrimination in biological assay systems. The single stereocenter also connected the two pharmacophores--a 2-nitroimidazole moiety critical to hypoxic cell radiosensitization, and a haloacetylcarbamoyl group to function as an anti-angiogenesis pharmacophore. In the chick embryo chorioallantoic membrane (CAM) assay, the R-enantiomers possessing the bulky p-tert-butylphenyl group showed higher anti-angiogenic activity than the corresponding S-enantiomers, while there were no differences in the activity between the enantiomers containing the less bulky methyl and tert-butyl groups. Among the compounds we report, R-p-tert-butylphenyl-bromoacetylcarbamoyl-2-nitroimidazole, TX-1898, was found to be the most promising candidate for further development of as anti-angiogenic hypoxic cell radiosensitizer.