A novel quantitative metric for joint space width: data from the Osteoarthritis Initiative (OAI).

OBJECTIVE: Joint space width (JSW) has been the gold standard to assess loss of cartilage in knee osteoarthritis (OA). Here we describe a novel quantitative measure of joint space width: standardized JSW (stdJSW). We assess the performance of this quantitative metric for JSW at tracking Osteoarthritis Research Society International (OARSI) joint space narrowing grade (JSN) changes and provide reference values for different JSN grades and their annual change. METHODS: We collected 18,934 individual knee images along with JSW and JSN readings from baseline up to month 48 (4 follow-ups) from the OAI study. Standardized JSW and 12-month JSN grade changes were calculated for each knee. For each JSN grade and 12-month grade change, the distribution of JSW loss was calculated for JSW and stdJSW. Area under the ROC curves was calculated on discrimination between different JSN grades for JSW and stdJSW. Standardized response mean (SRM) was used to compare the responsiveness of the two measures to changes in JSN grade. RESULTS: The areas under the receiver operating characteristic (ROC) curve (AUC) for stdJSW at discriminating between successive JSN grades were AUCstdJSW = 0.87, 0.95, and 0.96, for JSN>0, JSN>1 and JSN>2, respectively, whereas these were AUCfJSW = 0.79, 0.90, 0.98 for absolute JSW. We find that standardized JSW is significantly more responsive than absolute JSW, as measured by the SRM. CONCLUSIONS: Our results show that stdJSW outperforms absolute JSW at discriminating and tracking changes in JSN and further that this effect is in part because stdJSW cancels JSW variations attributed to patient height variations.

Matrix-associated autologous chondrocyte transplantation in a compartmentalized early stage of osteoarthritis.

OBJECTIVE: Cartilage restoration in joints with an early stage of osteoarthritis (OA) is an important clinical challenge. In this study, a compartmentalized, early-stage OA was generated surgically in sheep stifle joints, and this model was used to evaluate a matrix-associated cell transplantation approach for cartilage repair. METHOD: Eighteen sheep were operated twice. During the first operation, a unicompartmental OA in a stable joint was induced by creating a critical-size defect. The second operation served as a regeneration procedure. The eighteen sheep were divided into three groups. One group was treated with spongialization (SPONGIO), while the two others had spongialization followed by implantation of a hyaluronan matrix with (MACT) or without chondrocytes (MATRIX). The follow-up took place 4 months after the second operation. Gross Assessment of Joint Changes score and Brittberg score were used for the macroscopic evaluation, Mankin score, O'Driscoll score, and immunohistochemistry for collagen type I and type II for histological evaluation. RESULTS: The MACT group achieved significantly better results in both macroscopic and histological examinations. In the regeneration area, a Mankin score of 7.88 (6.20; 9.55) [mean (upper 95% confidence interval; lower 95% confidence interval)] was reached in the MACT group, 10.38 (8.03; 12.72) in the MATRIX group, and 10.33 (8.80; 11.87) in the SPONGIO group. The O'Driscoll score revealed a highly significant difference in the degree of defect repair: 15.92 (14.58; 17.25) for the MACT group compared to the two other groups [5.04 (1.21; 8.87) MATRIX and 6.58 (5.17; 8.00) SPONGIO; P < 0.0001]. CONCLUSION: This study demonstrates promising results toward the development of a biological regeneration technique for early-stage OA.

[Differential diagnostics of the musculoskeletal system in sports medicine]. / Differenzialdiagnostische Untersuchung in der Sportmedizin des Bewegungsapparats.

The positive effects of sports on the cardiovascular and musculoskeleal systems are widely accepted. Nevertheless, sports also can cause injury and overuse leading to sport-specific problems, which are often a challenge in diagnosing and treatment. The history of the sport-related injury is crucial for further differential diagnosis. Careful inspection, palpation and functional testing can reveal the possible pathology and lead to an effective strategy in the diagnostic assessment using radiographic tools such as sonography, X-ray and MR imaging (MRI). In muscle and tendon injuries sonography can provide ready to use information concerning muscle tears and tendon ruptures or degenerative lesions. Plain X-rays give a good overview on joint conditions regarding the bone and sometimes have to be completed by focused enlargement of the critical structure, especially in stress fractures and small bone lesions. MRT is the gold standard in the evaluation of interarticular and extra-articular sport-related pathologies, however, an exact clinical diagnosis allows a more effective investigation protocol. Profound knowledge of possible sport-specific injury and overuse patterns is necessary to detect lesions of the musculoskeletal system in active athletes and to use the fitting radiographic strategy for confirmation. The exact diagnosis is the prerequisite for initiating the appropriate treatment and a fast sports medical rehabilitation process.

Platelet-rich plasma (PRP) as therapy for cartilage, tendon and muscle damage - German working group position statement.

PURPOSE: Platelet rich plasma (PRP) is widely used in orthopaedics, but is still heavily debated. Therefore, a survey among the German "Working Group for Clinical Tissue Regeneration" of the German Society of Orthopaedics and Traumatology was conducted to achieve a consensus about the current therapeutical potential of PRP. METHODS: A first survey (n = 65 experts, all orthopaedic/trauma surgeons) was conducted (n = 13 questions). Following, a second round (n = 40 experts) was conducted with 31 questions to achieve consensus in 5 categories: three most common indications, PRP application, future research areas. RESULTS: Therapeutic PRP application was regarded as useful (89%), possibly even more important in the future (90%). Most common indications were tendon pathologies (77%), osteoarthritis (OA) (68%), muscle injuries (57%) and cartilage damage (51%). Consensus was reached in 16/31 statements. The application of PRP for early knee OA (Kellgren-Lawrence grade II) was regarded as potentially useful, as well as for acute and chronic tendinopathies. For chronic lesions (cartilage, tendons), multiple injections (2-4) were seen preferable to singular injections. However, no sufficient data exists on the time interval between the injections. Standardization of PRP preparation, application, frequency, as well as determining the range of indication is strongly recommended. CONCLUSIONS: There is a need of further standardization of the PRP preparation methods, indication and application protocols for knee OA and other indications, which must be further evaluated in basic science studies and randomized controlled clinical trials. LEVEL OF EVIDENCE: Consensus of expert opinion, Level V.

Tribocorrosion of a CoCrMo alloy sliding against articular cartilage and the impact of metal ion release on chondrocytes.

Partial knee replacement and hemiarthroplasty are some of the orthopedic procedures resulting in a metal on cartilage interface. As metal implant material, CoCrMo based alloys are commonly used. The aim of the present study is to assess the role of biotribocorrosion on the CoCrMo-cartilage interface with an emphasis on metal release during sliding contact. The biotribocorrosion experiments were performed under controlled electrochemical conditions using a floating cell with a three electrode set up coupled to a microtribometer. Throughout the experiment the coefficient of friction and the open circuit potential were monitored. Analyses of the electrolyte after the experiment show that metal release can occur during sliding contact of CoCrMo alloy against articular cartilage despite the extraordinary low coefficient of friction measured. Metal release is attributed to changes in passive layer caused at the onset of sliding. The released metal was found to be forming compounds with potential cytotoxicity. Since the presence of metal ions in the cartilage matrix can potentially lead to cell apoptosis, the metabolic activity of human osteoarthritic chondrocytes (2D-cultures) was investigated in the presence of phosphate buffered saline containing metal ions using XTT-assay. The experiments indicate that critical concentrations of Co ions lead to a significant decrease in chondrocyte metabolic activity. Therefore, biotribocorrosion is a mechanism that can occur in partial replacements and lead to chondrocyte apoptosis thus playing a role in the observed accelerated degradation of the remaining cartilage tissue after the mentioned orthopedic procedures. STATEMENT OF SIGNIFICANCE: Partial replacements provide an alternative to total joint replacements. This procedure is less invasive, allows a faster rehabilitation and provides a better function of the joint. However, the remaining native cartilage experiences accelerated degradation when in contact with metallic implant components. This work investigates the role of tribocorrosion at the metal-cartilage interface during sliding. Tribocorrosion is a degradation process that can alter significantly the wear rates experienced by metallic implants and lead to the release of metal ions and particles. The released metal can form compounds with potential cytotoxicity on cartilage tissue. The knowledge gained in this work will serve to understand the mechanisms behind the failure of partial replacements and develop future biomaterials with an enhanced lifetime.

Effects of a lower extremity exercise program on gait biomechanics and clinical outcomes in children and adolescents with obesity: A randomized controlled trial.

BACKGROUND: Research highlights the detrimental effects of obesity on gait biomechanics and the accompanied risk of lower-extremity skeletal malalignments, increased joint stress, pain and discomfort. Individuals with obesity typically show increased knee valgus angles combined with an increased step width. Accompanying muscular dysfunctions impede their ability to compensate for these alterations, especially in the frontal plane. To date, no studies are available, which evaluated the potential effects of an exercise program (EP) in reducing these unfavorable biomechanical changes. RESEARCH QUESTIONS: Is a 12-week EP, which includes hip abductor and knee extensor strength exercises and fosters dynamic knee alignment, effective in positively altering gait biomechanics in children and adolescents with obesity? METHODS: This study was a randomized controlled trial having children and adolescents with obesity assigned to an EP (n = 19) or control (n = 16) group. Pain, self-rated knee function, muscle strength and 3D gait analysis during walking and stair climbing were evaluated. RESULTS: Results indicate that the EP was able to increase muscular strength especially in the hip abductors. In addition, children from the EP group walked with less maximum hip adduction and reduced pelvic drop during weight acceptance at follow-up. No changes were present in self-rated knee function, pain or discomfort. SIGNIFICANCE: Even though effects were small, results indicate that an EP is an effective short-term possibility to counteract the progressive development of biomechanical malalignments of the lower extremity. Clinical parameters indicated that the program was feasible. Nonetheless, low adherence highlights the need to develop more attractive programs. CLINICAL TRIALS REG. NO: clinicaltrials.gov (NCT02545764).

Results of chondrocyte implantation with a fibrin-hyaluronan matrix: a preliminary study.

UNLABELLED: Fibrin, a homologous polymer, is the natural scaffold of wound healing and therefore a candidate as a carrier for cell transplantation. We explored a novel matrix-based implant cartilage repair composed of both fibrin and hyaluronan in a defined ratio that takes advantage of the biological and mechanical properties of these two elements. The matrix was seeded with autologous chondrocytes expanded in the presence of a proprietary growth factor variant designed to preserve their chondrogenic potential. We prospectively followed eight patients with symptomatic-chronic cartilage defects treated with this carrier. Patients had arthroscopy to harvest autologous chondrocytes then grown in autologous serum. Chondrocytes were cultured in the presence of the FGF variant and then seeded on the fibrin-hyaluronan matrix. About 4 weeks following biopsy, the patients underwent implantation of the constructs by miniarthrotomy. Three of the eight patients had transient effusion. Clinical performance was measured by Lysholm and IKDC scores, MRI, and the need for secondary surgery. The clinical outcome of a 1-year followup demonstrated increase of clinical scores. The MRI followup showed good filling of the defect with tissue having the imaging appearance of cartilage in all patients. Apart from the transient effusion in three patients we observed no other adverse events during the followup. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Three-year clinical outcome after chondrocyte transplantation using a hyaluronan matrix for cartilage repair.

Repair of articular cartilage represents a significant clinical problem and although various new techniques - including the use of autologous chondrocytes - have been developed within the last century the clinical efficacy of these procedures is still discussed controversially. Although autologous chondrocyte transplantation (ACT) has been widely used with success, it has several inherent limitations, including its invasive nature and problems related to the use of the periosteal flap. To overcome these problems autologous chondrocytes transplantation combined with the use of biodegradable scaffolds has received wide attention. Among these, a hyaluronan-based scaffold has been found useful for inducing hyaline cartilage regeneration. In the present study, we have investigated the mid-term efficacy and safety of Hyalograft C grafts in a group of 36 patients undergoing surgery for chronic cartilage lesions of the knee. Clinical Outcome was assessed prospectively before and at 12, 24, and 36 months after surgery. No major adverse events have been reported during the 3-year follow-up. Significant improvements of the evaluated scores were observed (P < 0.02) at 1 year and a continued increase of clinical performance was evident at 2 and 3 years follow-up. Patients under 30 years of age with single lesions showed statistically significant improvements at all follow-up visits compared to those over 30 with multiple defects (P < 0.01). Hyalograft C compares favorably with classic ACT and is particularly indicated in younger patients with single lesions. The graft can be implanted through a miniarthrotomy and needs no additional fixation with sutures except optional fibrin gluing at the defect borders. These results suggest that Hyalograft C is a valid alternative to ACT.

Repair of articular cartilage defects treated by microfracture and a three-dimensional collagen matrix.

The objective of our study was to evaluate the behavior of ovine chondrocytes and bone marrow stromal cells (BMSC) on a matrix comprising type-I, -II, and -III collagen in vitro, and the healing of chondral defects in an ovine model treated with the matrix, either unseeded or seeded with autologous chondrocytes, combined with microfracture treatment. For in vitro investigation, ovine chondrocytes and BMSC were seeded on the matrix and cultured at different time points. Histological analysis, immunohistochemistry, biochemical assays for glycosaminoglycans, and real-time quantitative PCR for collagens were performed. The animal study described here included 22 chondral defects in 11 sheep, divided into four treatment groups. Group A: microfracture and collagen matrix seeded with chondrocytes; B: microfracture and unseeded matrices; C: microfracture; D: untreated defects. All animals were sacrificed 16 weeks after implantation, and a histomorphometrical and qualitative evaluation of the defects was performed. The in vitro investigation revealed viable cells up to 3 weeks; chondrocytes had a predominantly round morphology, produced glycosaminoglycans, and expressed both collagen markers, whereas BMSC stained positive for antibodies against type-II collagen; however, no mRNA for type-II collagen was amplified. All treatment groups of the animal model showed better defect filling compared to untreated knees. The cell-seeded group had the greatest quantity of repair tissue and the largest quantity of hyaline-like tissue. Although the collagen matrix is an adequate environment for BMSC in vitro, the additionally implanted unseeded collagen matrix did not increase the repair response after microfracture in chondral defects. Only the matrices seeded with autologous cells in combination with microfracture were able to facilitate the regeneration of hyaline-like cartilage.

Matrix collagen type and pore size influence behaviour of seeded canine chondrocytes.

This study directly compared the behaviour of chondrocytes in porous matrices comprising different collagen types and different pore diameters. There was a dramatic difference in the morphology of the cells in the type I and type II collagen matrices. The cells in the type II collagen matrix retained their chondrocytic morphology and synthesized glycosaminoglycans, while in the type I matrix the chondrocytes displayed a fibroblastic morphology with less biosynthetic activity than those in the type II. Small pore diameter affected morphology initially in the type I matrices and showed a higher increase of DNA content, but with time the cells lost the chondrocytic morphology. Our results demonstrate the marked influence of collagen type and pore characteristics on the phenotypic expression of seeded chondrocytes.

Chondrocyte-seeded collagen matrices implanted in a chondral defect in a canine model.

The objective of our study was to evaluate reparative tissues formed in chondral defects in an adult canine model implanted with cultured autologous articular chondrocytes seeded in type I and II collagen GAG matrices. Two defects were produced in the trochlea grooves of the knees of 21 dogs, with cartilage removed down to the tidemark. This study includes the evaluation of 36 defects distributed among five treatment groups: Group A, type II collagen matrix seeded with autologous chondrocytes under a sutured type II collagen flap; Group B, type I collagen matrices seeded with chondrocytes under a sutured fascia flap; Group C, unseeded type I collagen matrix implanted under a sutured fascia flap; Group D, fascia lata flap alone; and Group E, untreated defects. All animals were killed 15 weeks after implantation. Six other defects were created at the time of death and evaluated immediately after production as 'acute defect controls'. In three additional defects, unseeded matrices were sutured to the defect and the knee closed and reopened after 30 min to determine if early displacement of the graft was occurring; these defects served as 'acute implant controls'. The areal percentages of four tissue types in the chondral zone of the original defect were determined histomorphometrically: fibrous tissue (FT); hyaline cartilage (HC); transitional tissue (TT, including fibrocartilage); and articular cartilage (AC). New tissue formed in the remodeling subchondral bone underlying certain defects was also assessed. Bonding of the repair tissue to the subchondral plate and adjacent cartilage, and degradation of the adjacent tissues were evaluated. There were no significant differences in the tissues filling the original defect area of the sites treated with chondrocyte-seeded type I and type II matrices. Most of the tissue in the area of the original defect in all of the groups was FT and TT. The areal percentage of HC plus AC was highest in group E, with little such tissue in the cell-seeded groups, and none in groups C and D. The greatest total amount of reparative tissue, however, was found in the cell-seeded type II matrix group. Moreover, examination of the reparative tissue formed in the subchondral region of defects treated with the chondrocyte-seeded collagen matrices (Groups A and B) demonstrated that the majority of the tissue was positive for type II collagen and stained with safranin O. These results indicate an influence of the exogenous chondrocytes on the process of chondrogenesis in this site. In all groups with implants (A-D), 30(50% of the FT and TT was bonded to the adjacent cartilage. Little of this tissue (6-22%) was attached to the subchondral plate, which was only about 50% intact. Remarkable suture damage was found in sections from each group in which sutures were used. Harvest sites showed no regeneration of normal articular cartilage, 18 weeks after the biopsy procedure. Future studies need to investigate other matrix characteristics, and the effects of cell density and incubation of the seeded sponges prior to implantation on the regenerative response.

Articular cartilage chondrocytes in type I and type II collagen-GAG matrices exhibit contractile behavior in vitro.

Natural healing of articular cartilage defects generally does not occur, and untreated lesions may predispose the joint to osteoarthritis. To promote healing of cartilage defects, many researchers are turning toward a tissue engineering approach involving cultured cells and/or porous, resorbable matrices. This study investigated the contractile behavior of cultured canine chondrocytes seeded in a porous collagen-glycosaminoglycan (GAG) scaffold. Chondrocytes isolated from the knee joints of adult canines and expanded in monolayer culture were seeded into porous collagen-GAG scaffolds. Scaffolds were of two different compositions, with the predominant collagen being either type I or type II collagen, and of varying pore diameters. Over the 4-week culture period, the seeded cells contracted all of the type I and type II collagen-based matrices, despite a wide range of stiffness (145 +/- 23 Pa, for the type I scaffold, to 732 +/- 35 Pa, for the type II material). Pore diameter (25-85 microm, type I; and 53-257 microm, type II) did not affect cell-mediated contraction. Immunohistochemical staining revealed the presence of alpha-smooth muscle actin, an isoform responsible for contraction of smooth muscle cells and myofibroblasts, in the cytoplasm of the seeded cells and in chondrocytes in normal adult canine articular cartilage.

Autologous chondrocyte implantation in a canine model: change in composition of reparative tissue with time.

The objective of the study was to evaluate the tissue types filling 4-mm diameter defects in the canine trochlear groove 1.5, 3, and 6 months after autologous chondrocyte implantation (ACI). Untreated defects served as controls. Periosteum alone controls were also included at the 1.5-month time period. The results were compared with previously published findings obtained 12 and 18 months postoperative. After 3 months the ACI-treated defects contained significantly more reparative tissue than found in the untreated control group, including twice the amount of hyaline cartilage (HC). These findings, however, were the only significant effects of the ACI treatment when compared to the periosteum alone or empty control groups. The benefits of ACI found at 3 months did not persist to longer time periods. An evaluation of the inter-observer error associated with the histomorphometric method indicated that it was generally less than the inter-animal variation in the results.

Effect of cultured autologous chondrocytes on repair of chondral defects in a canine model.

Articular cartilage has a limited capacity for repair. In recent clinical and animal experiments, investigators have attempted to elicit the repair of defects of articular cartilage by injecting cultured autologous chondrocytes under a periosteal flap (a layer of periosteum). The objective of the present study was to determine the effect of cultured autologous chondrocytes on healing in an adult canine model with use of histomorphometric methods to assess the degree of repair. A total of forty-four four-millimeter-diameter circular defects were created down to the zone of calcified cartilage in the articular cartilage of the trochlear groove of the distal part of the femur in fourteen dogs. The morphology and characteristics of the original defects were defined in an additional six freshly created defects in three other dogs. Some residual noncalcified articular cartilage, occupying approximately 2 per cent of the total cross-sectional area of the defect, was sometimes left in the defect. The procedure sometimes damaged the calcified cartilage, resulting in occasional microfractures or larger fractures, thinning of the zone of calcified cartilage, or, rarely, small localized penetrations into subchondral bone. The forty-four defects were divided into three treatment groups. In one group, cultured autologous chondrocytes were implanted under a periosteal flap. In the second group, the defect was covered with a periosteal flap but no autologous chondrocytes were implanted. In the third group (the control group), the defects were left empty. The defects were analyzed after twelve or eighteen months of healing. Histomorphometric measurements were made of the percentage of the total area of the defect that became filled with repair tissue, the types of tissue that filled the defect, and the integration of the repair tissue with the adjacent cartilage at the sides of the defects and with the calcified cartilage at the base of the defect. In histological sections made through the center of the defects in the three groups, the area of the defect that filled with new repair tissue ranged from a mean total value of 36 to 76 per cent, with 10 to 23 per cent of the total area consisting of hyaline cartilage. Integration of the repair tissue with the adjacent cartilage at the edges of the defect ranged from 16 to 32 per cent in the three groups. Bonding between the repair tissue and the calcified cartilage at the base of the defect ranged from 41 to 89 per cent. With the numbers available, we could detect no significant difference among the three groups with regard to any of the parameters used to assess the quality of the repair. In the two groups in which a periosteal flap was sutured to the articular cartilage surrounding the defect, the articular cartilage showed degenerative changes that appeared to be related to that suturing.

Current concepts in the treatment of articular cartilage defects.

Over time, articular cartilage loses the capacity to regenerate itself, making repair of articular surfaces difficult. Lavage and debridement may offer temporary relief of pain for up to 4.5 years, but offer no prospect of long-term cure. Likewise, marrow-stimulation techniques such as drilling, microfracture, or abrasion arthroplasty fail to yield long-term solutions because they typically promote the development of fibrocartilage. Fibrocartilage lacks the durability and many of the mechanical properties of the hyaline cartilage that normally covers articular surfaces. Repair tissue resembling hyaline cartilage can be induced to fill in articular defects by using perichondrial and periosteal grafts. However, these techniques are limited by the amount of tissue available for grafting and the tendency toward ossification of the repair tissue. Autogenous osteochondral arthroscopically implanted grafts (mosaicplasty), or open implantation of lateral patellar facet (Outerbridge technique), requires violation of subchondral bone. Osteochondral allografts risk viral transmission of disease and low chondrocyte viability, in addition to removal of host bone for implantation. Autologous chondrocyte implantation offers the opportunity to achieve biologic repair, enabling the surgeon to repair the joint surface with autologous articular cartilage. With this technique, care must be taken to ensure the safety, viability, and microbial integrity of the autologous cells while they are expanded in culture over a 4- to 5-week period prior to implantation. Surgical implantation requires equal attention to meticulous technique. In the future, physiologic repair also may become possible using mesenchymal stem cells or chondrocytes delivered surgically in an ex vivo-derived matrix. This would allow in vitro manipulation of cells with growth factors, mechanical stimuli, and matrix sizing to allow implantation of mature biosynthetic grafts which would allow treatment of larger defects with decreased rehabilitation and morbidity.

Microfracture in the Ankle: Clinical Results and MRI with T2-Mapping at 3.0 T after 1 to 8 Years.

BACKGROUND: Microfracture (MFX) is frequently used to treat deep cartilage defects in the ankle; however, the data on repair tissue (RT) quality after MFX are very limited at this time. T2-mapping at 3 T has been optimized for the ankle and can be used to noninvasively evaluate cartilage collagen and water content. The aim of this study was to determine if the RT after MFX in the ankle had T2 properties similar to the adjacent reference cartilage (RC). METHODS: Fourteen cases after MFX in the ankle were assessed with morphological MRI and T2-mapping at 3 T. The American Orthopaedic Foot and Ankle Society (AOFAS) score and a modified Cinicinnati Knee Rating System rating were used to evaluate the clinical outcome. The MRI protocol included a 3-dimensional sequence and a proton-density sequence for morphological evaluation and a multiecho spin echo sequence for T2-mapping. Region of interest analyses were carried out in accordance with the morphological images to ensure complete coverage of the defect site. RESULTS: Both clinical scores demonstrated significant improvement at the time of the MR examination (P < 0.001). RT T2 was 49.3 ± 10.1 (range, 35.7-69.3) milliseconds, and RC T2 was 49.9 ± 8.2 (range, 38.4-63.7) milliseconds (P = 0.838). Relative T2 (rT2) was 1.00 ± 0.20 (range, 0.72-1.36). CONCLUSION: MFX in the ankle can provide RT with T2 properties similar to adjacent cartilage.

T2 mapping and dGEMRIC after autologous chondrocyte implantation with a fibrin-based scaffold in the knee: preliminary results.

OBJECTIVE: To assess repair tissue (RT) after the implantation of BioCartII, an autologous chondrocyte implantation (ACI) technique with a fibrin-hyaluronan polymer as scaffold. T2 mapping and delayed Gadolinium Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) were used to gain first data on the biochemical properties of BioCartII RT in vivo. METHODS: T2 mapping and dGEMRIC were performed at 3T in five patients (six knee joints) who had undergone ACI 15-27 months before. T2 maps were obtained using a pixel wise, mono-exponential non-negative least squares fit analysis. For quantitative T1 mapping a dual flip angle 3D GRE sequence was used and T1 maps were calculated pre- and post-contrast using IDL software. Subsequent region of interest analysis was carried out in comparison with morphologic MRI. RESULTS: A spatial variation of T2 values in both hyaline, normal cartilage (NC) and RT was found. Mean RT T2 values and mean NC T2 values did not differ significantly. Relative T2 values were calculated from global RT and NC T2 and showed a small range (0.84-1.07). The relative delta relaxation rates (rDeltaR1) obtained from the T1 maps had a wider range (0.77-4.91). CONCLUSION: T2 mapping and dGEMRIC provided complementary information on the biochemical properties of the repair tissue. BioCartII apparently can provide RT similar to hyaline articular cartilage and may become a less-invasive alternative to ACI with a periosteal flap.

Lectin binding patterns reflect the phenotypic status of in vitro chondrocyte models.

In vitro studies using chondrocyte cell cultures have increased our understanding of cartilage physiology and the altered chondrocytic cell phenotype in joint diseases. Beside the use of primary cells isolated from cartilage specimens of donors, immortalized chondrocyte cell lines such as C-28/I2 and T/C-28a2 have facilitated reproducible and standardized experiments. Although carbohydrate structures appear of significance for cartilage function, the contribution of the chondrocyte glycocalyx to matrix assembly and alterations of the chondrocyte phenotype is poorly understood. Therefore, the present study aimed to evaluate the glycoprofile of primary human chondrocytes as well as of C-28/I2 and T/C-28a2 cells in culture. First, the chondrocytic phenotype of primary and immortalized cells was assessed using real-time reverse transcriptase polymerase chain reaction, immunofluorescence, and glycosaminoglycans staining. Then, a panel of lectins was selected to probe for a range of oligosaccharide sequences determining specific products of the O-glycosylation and N-glycosylation pathways. We found that differences in the molecular phenotype between primary chondrocytes and the immortalized chondrocyte cell models C-28/I2 and T/C-28a2 are reflected in the glycoprofile of the cells. In this regard, the glycocalyx of immortalized chondrocytes was characterized by reduced levels of high-mannose type and sialic acid-capped N-glycans as well as increased fucosylated O-glycosylation products. In summary, the present report emphasizes the glycophenotype as an integral part of the chondrocyte phenotype and points at a significant role of the glycophenotype in chondrocyte differentiation.