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PubMed2003

Regulation of nitric oxide production in osteoarthritic and rheumatoid cartilage. Role of endogenous IL-1 inhibitors.

OBJECTIVE: To investigate the endogenous regulation of interleukin-1 (IL-1) cytokine network in osteoarthritic (OA) and rheumatoid (RA) cartilage in relation to nitric oxide (NO) production. METHODS: Cartilage specimen obtained from OA and RA patients undergoing knee replacement surgery were studied for iNOS expression, NO and IL-1 antagonist production in tissue culture. RESULTS: OA cartilage responded to IL-1beta-stimulation with higher NO production than RA cartilage, whereas there was no difference in NO synthesis between OA and RA samples when stimulated by TNFalpha or LPS. Interleukin-1 receptor antagonist (IL-1Ra) production was higher in RA cartilage than in OA cartilage, and its production was increased by NO synthase inhibitor 1400W. CONCLUSION: IL-1beta is a potent stimulator of NO production by the iNOS pathway in RA and more pronouncedly in OA cartilage. This process is regulated by cartilage derived IL-1 antagonists, and is implicated in cartilage destruction and synovial inflammation in OA and RA joints.

Aged↗
PubMed1999

The distribution of YKL-40 in osteoarthritic and normal human articular cartilage.

YKL-40, also called human cartilage glycoprotein-39, is a major secretory protein of human chondrocytes in cell culture. YKL-40 mRNA is expressed by cartilage from patients with rheumatoid arthritis, but is not detectable in normal human cartilage. The aim was to investigate the distribution of YKL-40 in osteoarthritic (n=9) and macroscopically normal (n=5) human articular cartilage, collected from 12 pre-selected areas of the femoral head, to discover a potential role for YKL-40 in cartilage remodelling in osteoarthritis. Immunohistochemical analysis showed that YKL-40 staining was found in chondrocytes of osteoarthritic cartilage mainly in the superficial and middle zone of the cartilage rather than the deep zone. There was a tendency for high number of YKL-40 positive chondrocytes in areas of the femoral head with a considerable biomechanical load. The number of chondrocytes with a positive staining for YKL-40 was in general low in normal cartilage. The present findings, together with previous observations, suggests that YKL-40 may be of importance in cartilage remodelling/degradation of osteoarthritic joints.

Adipokines↗
PubMed2003

MT1-MMP-dependent, apoptotic remodeling of unmineralized cartilage: a critical process in skeletal growth.

Skeletal tissues develop either by intramembranous ossification, where bone is formed within a soft connective tissue, or by endochondral ossification. The latter proceeds via cartilage anlagen, which through hypertrophy, mineralization, and partial resorption ultimately provides scaffolding for bone formation. Here, we describe a novel and essential mechanism governing remodeling of unmineralized cartilage anlagen into membranous bone, as well as tendons and ligaments. Membrane-type 1 matrix metalloproteinase (MT1-MMP)-dependent dissolution of unmineralized cartilages, coupled with apoptosis of nonhypertrophic chondrocytes, mediates remodeling of these cartilages into other tissues. The MT1-MMP deficiency disrupts this process and uncouples apoptotic demise of chondrocytes and cartilage degradation, resulting in the persistence of "ghost" cartilages with adverse effects on skeletal integrity. Some cells entrapped in these ghost cartilages escape apoptosis, maintain DNA synthesis, and assume phenotypes normally found in the tissues replacing unmineralized cartilages. The coordinated apoptosis and matrix metalloproteinase-directed cartilage dissolution is akin to metamorphosis and may thus represent its evolutionary legacy in mammals.

Animals↗
PubMed1960

Comparison of the effects of papain n vitamin A on cartilage. I. The effects in rabbits.

The administration of large amounts of vitamin A to rabbits has been shown to result in depletion of cartilage matrix. The normal basophilic, metachromatic, and Alcian blue staining properties of the matrix are lost, especially in articular and epiphyseal cartilage. The cartilage cells remain intact, but are reduced in size. These changes sometimes appeared as early as 48 hours after the initiation of daily injection of 1 million units of vitamin A, and were usually well established by 5 days. Some rabbits failed to show changes in cartilage, even after 5 daily injections. Increased amounts of material presumed to be chondroitin sulfate were present in the sera of vitamin A-treated rabbits, usually by 72 hours after the first injection. This was demonstrated by a turbidimetric procedure using hexamminecobaltic chloride. In rabbits given sulfur-35 (Na(2)S(35)O(4)) 5 days before the initiation of vitamin A treatment, it was shown that sulfur-35 was lost from articular and epiphyseal cartilage. This was associated with an increase in the non-dialyzable sulfur-35 in both serum and in the cobalt-precipitable material. These rabbits also excreted more sulfur-35 than rabbits not given vitamin A. There was a reduction in sulfur-35 activity in chondromucoprotein extracted from the ear cartilage of vitamin A-treated rabbits. The changes are interpreted as indicating that the administration of large amounts of vitamin A to rabbits results in removal of chondroitin sulfate from cartilage matrix. The administration of small amounts of crude papain causes histologic changes in cartilage that are remarkably similar to those seen in vitamin A-treated rabbits. The possibility is suggested that the changes in cartilage produced by administration of vitamin A to rabbits may be the result of activation of a proteolytic enzyme or enzymes, with properties similar to those of papain.

Animals↗
PubMed2001

Validation of a simple histological-histochemical cartilage scoring system.

In this study, we assessed the validity of a subjective histological-histochemical scoring system as compared to an automated histomorphometry program for analyzing cartilage repair tissue. In the first part of the study, we assessed the ability of the human eye to estimate the percent cartilage in a histological section. Twenty-nine rabbit periosteal explants that had been cultured in agarose transforming growth factor-beta (TGF-beta) were selected so that the percentage of cartilage in the specimens was distributed equally from 0% to 100%. Color photomicrographs were evaluated by 5 expert observers who gave a visual estimate of the percent cartilage. There was a strong correlation between the estimated and actual percent cartilage (R(2) = 0.92, p < 0.0001) and among the observers (I.C.C. = 0.89). On average, the estimated percent cartilage was within ten percent of the actual percent measured. In the second part, we compared the data derived using a simple cartilage score with those obtained by automated image analysis. The histological slides from 159 explants cultured under various experimental conditions (14 treatment groups) in two different experiments were analyzed. The cartilage content was estimated visually and a score from 0 to 3 was assigned. A previously validated, computerized image analysis system was used to measure the actual percent cartilage. Statistical analyses revealed a good linear regression (R(2) = 0.84, p = 0.0001), and even better polynomial correlation between the actual measurement and the score (R(2) = 0.88, p = 0.0001). These data demonstrate the validity of a simple histological-histochemical subjective scoring system. A computerized automated program such as the one employed in this study is preferable due to its many advantages. However, a subjective scoring system may be appropriate to use when the funding and expertise required for a computerized image analysis program are not available.

Animals↗
PubMed1998

Stimulation of cartilage differentiation by osteogenic protein-1 in cultures of human perichondrium.

Exposure of progenitor cells with chondrogenic potential to recombinant human osteogenic protein-1 [rhOP-1, or bone morphogenetic protein-7 (BMP-7] may be of therapeutic interest in the regeneration of articular cartilage. Therefore, in this study, we examined the influence of rhOP-1 on cartilage formation by human perichondrium tissue containing progenitor cells with chondrogenic potential in vitro. Fragments of outer ear perichondrium tissue were embedded in clotting autologous blood to which rhOP-1 had been added or not (controls), and the resulting explant was cultured for 3 weeks without further addition of rhOP-1. Cartilage formation was monitored biochemically by measuring [&sup35;S]sulfate incorporation into proteoglycans and histologically by monitoring the presence of metachromatic matrix with cells in nests. The presence of rhOP-1 in the explant at the beginning of culture stimulated [&sup35;S]sulfate incorporation into proteoglycans in a dose-dependent manner after 3 weeks of culture. Maximal stimulation was reached at 40 microgram/ml. Histology revealed that explants treated with 20-200 microgram/ml rhOP-1, but not untreated control explants, contained areas of metachromatic-staining matrix with chondrocytes in cell nests. These results suggest that rhOP-1 stimulates differentiation of cartilage from perichondrium tissue. The direct actions of rhOP-1 on perichondrium cells to stimulate chondrocytic differentiation and production of cartilage matrix in vitro provide a cellular mechanism for the induction of cartilage formation by rhOP-1 in vivo. Thus, rhOP-1 may promote early steps in the cascade of events leading to cartilage formation. Therefore, rhOP-1 could be an interesting factor for regeneration of cartilage in articular cartilage defects.

Adolescent↗
PubMed2006

Review of injectable cartilage engineering using fibrin gel in mice and swine models.

More than a decade of work has been devoted to engineering cartilage for articular surface repair. This review covers the use of fibrin gel polymer as an injectable scaffold for generating new cartilage matrix from isolated articular chondrocytes beginning with studies in mice and culminating in an applied study in swine joints. These studies began with developing a formulation of fibrin that was injectable and promoted cartilage matrix formation. Subsequent studies addressed the problems of volume loss after the scaffolds were placed in vivo by adding lyophilized cartilage matrix. Additional studies focused on the ability of isolated chondrocytes to heal and repair cartilage in a model that could be biomechanically tested. In conclusion, this series of studies demonstrated that fibrin gel is a suitable polymer gel for generating new cartilage matrix from articular chondrocytes. The new matrix is capable of forming mechanical bonds between cartilage disks and can lead to healing and integration. Armed with these results, implantation of fibrin-cell constructs into defects in swine knees showed new cartilage formation and filling of the defects. Continuing work in these models with fibrin and other polymerizable hydrogels could result in a suitable cell-based therapy for articular cartilage lesions.

Animals↗
PubMed1979

The effect of aging on the synthesis of hexosamine-containing substances from rat costal cartilage. A decrease in sulfation of chondroitin sulfate with aging.

The amount of glycosaminoglycan (GAG) in dry costal cartilage tissue of rats decreased with aging, while the GAG content in mg DNA (unit cartilage cell) remained the same with aging. These results can be explained by the finding that the total number of cartilage cells decreased with aging. Electrophoretic analysis showed that chondroitin 4-sulfate was the major GAG in rat costal cartilage of various ages. Rat costal cartilage of different ages was incubated with radioactive precursors, and newly synthesized GAG was prepared and the radioactivity analyzed to determine the biosynthetic activity. As to changes in the radioactivity uptake with aging per mg dry cartilage tissue, aging influenced [35S]sulfate incorporation into GAG more significantly than [3H]glucosamine incorporation into GAG. There was a significant decrease in the specific radioactivity of [35S]sulfate per mg DNA (unit cartilage cell), whereas the specific radioactivity of [3H]glucosamine per mg DNA did not change significantly with aging. Both the total sulfotransferase activity and the specific activity per mg DNA decreased significantly with aging. Analysis of disaccharide units formed after chondroitinase ABC digestion of labeled GAG isolated from young and old cartilage showed that the percentage of incorporation of [3H]glucosamine into deltaDi-OS increased significantly with aging. These results suggested that the appearance of nonsulfated positions in the structure of the chondroitin sulfate chain increased with aging. On the basis of gel chromatography on Bio-Gel A-1.5 m no significant difference in the approximate molecular size of chondroitin sulfate was observed between the young and old GAG samples. The present study indicated that the sulfation of chondroitin sulfate chains from rat costal cartilage decreased with the process of aging.

Aging↗
PubMed1991

Role of TNF alpha, in relation to IL-1 and IL-6 in the proteoglycan turnover of human articular cartilage.

In both young and old human articular cartilage explants, TNF alpha induced a concentration-dependent, reversible suppression of the proteoglycan (PG) synthesis. Young cartilage was more sensitive to TNF alpha than old cartilage: 50% suppression of PG synthesis was reached at a TNF alpha concentration of 5 U/ml for young and 30 U/ml for old cartilage, whereas at 10(3) U/ml the PG synthesis of young cartilage was blocked and that of old cartilage suppressed by 80%. These inhibition levels of PG synthesis resulted in 25% PG depletion of the explants after 8 days of culture. The release of cartilage PG was not enhanced. TNF alpha induced no detectable amounts of IL-1 (less than 0.01 U) in young or old cartilage but did induce IL-6 production. The induced amounts of IL-6 were higher in young than in old cartilage but no dose-dependency was evident. Antibodies to neither IL-1 nor IL-6 had any influence on the TNF alpha-induced suppression of PG synthesis. The combination of TNF alpha and IL-1 led to an additive inhibition of PG synthesis which had no relationship to induced IL-6. TNF alpha was about 100-fold less active than IL-1.

Aging↗
PubMed2002

Sacral and iliac articular cartilage thickness and cellularity: relationship to subchondral bone end-plate thickness and cancellous bone density.

OBJECTIVES: To measure the thickness and cellularity of adult human sacral and iliac articular cartilages and the thickness and density of the subchondral bones. METHODS: The right sacroiliac joints of 15 adult patients were examined post-mortem. HOME (Highly Optimized Microscope Environment) microscopy was used to measure articular cartilage and subchondral bone end-plate thickness. Conventional morphometric techniques were employed to estimate cartilage cellularity and cancellous bone density. RESULTS: Sacral articular cartilage was thicker than iliac (1.81 vs 0.80 mm, P<0.001). Iliac cartilage cell density in all zones was higher than sacral. The overall mean was 31.19 x 10(-3) vs. 23.23 x 10(-3)/mm(3), P<0.001. Superficial zones contained more cells than middle and deep zones but there were large differences between the cell numbers of the middle and deep zones of both sacral and iliac cartilages. Iliac subchondral bone end-plates were thicker than sacral (0.36 vs 0.23 mm, P<0.001). The thickness of these plates was related inversely to that of the overlying articular cartilages. Iliac subchondral cancellous bone was twice as dense as sacral (22.07 vs. 12.05%, P<0.001), a ratio recognized anteriorly, centrally and posteriorly. CONCLUSIONS: Adult human sacral cartilage is thick and of low cell density. It rests upon a thin bone end-plate supported by porous, cancellous bone. Iliac cartilage and bone display the converse proportions. The identification of these variables may assist understanding of normal sacroiliac joint function and the interpretation of tissue changes in the spondylarthropathies.

Adult↗
PubMed2003

Sex differences in knee cartilage volume in adults: role of body and bone size, age and physical activity.

OBJECTIVE: To test the hypothesis that sex differences in knee cartilage volume may be mediated through body and bone size, age and/or physical activity. METHODS: A cross-sectional convenience sample of 372 subjects (males 43%; mean age 45 yr, range 26-61) was studied. Articular cartilage volumes and bone size were determined at the patella, medial and lateral tibia by processing images acquired in the sagittal plane using T1-weighted fat saturation magnetic resonance imaging. Height, weight, physical activity (lower limb muscle strength, endurance fitness and questionnaire items) and radiographic osteoarthritis (ROA) were measured. RESULTS: Gender explained 33-42% of the variation in knee cartilage volumes (all P < 0.001). Males had 33-42% higher cartilage volume than females at all sites. In the whole group, the magnitude of sex differences decreased to 8-18% after adjustment for body height, weight and bone size, but remained significant (all P < 0.05). Further adjustment for physical activity had no effect on the sex differences. The sex differences in cartilage volume were greater in those aged over 50 compared with those aged under 50 (P < 0.05 for age-sex interaction at all sites) and were independent of ROA. CONCLUSIONS: Men have substantially higher knee cartilage volumes than women. These sex differences appear to be mediated in part by body and bone size but a significant amount remains unexplained. Furthermore, the differences become more marked over the age of 50 yr suggesting that both cartilage development and cartilage loss in later life contribute to sex differences in cartilage volume. Further longitudinal studies in large samples will be required to confirm these findings.

Adult↗
PubMed2003

Magnetic resonance imaging of focal articular cartilage lesions.

Lesions of the articular cartilage now are recognized as a common, often treatable source of joint disability. Magnetic resonance imaging (MRI) of articular cartilage is a sensitive, noninvasive method for the detection of focal articular cartilage lesions. Advancement in imaging technology now allows for high spatial resolution acquisitions that are able to identify most cartilage lesions, and these acquisitions can be incorporated into everyday clinical imaging protocols. Thus, screening for cartilage abnormalities can be accomplished, along with routine evaluation for ligament and meniscal abnormalities. Familiarity with the appearances of normal cartilage and the full spectrum of cartilage lesions will aid in specific diagnoses. Grading and sizing of cartilage lesions and any underlying bony abnormalities on MRI can help the surgeon in treatment planning; however, some significant cartilage lesions can be difficult to identify and grade by MRI.

Adolescent↗
PubMed1975

Morphological and biochemical studies during differentiation and calcification of fracture callus cartilage.

Differentiation and calcification of cartilage of a fracture callus morphologically, ultrastructurally, and histochemically resembles cartilage of growing epiphyseal plate. The fracture callus includes the various cartilage cell types found in the epiphyseal plate. Proliferating and hypertrophic cartilage had higher activities of cytochrome oxidase, alkaline phosphatase and glutamate aspartate transaminase than fibrocartilage. Enzymes controlling glycogen synthesis and glycolysis had higher levels of activity in fibrocartilage than in hypertrophic cartilage. Lysosomal enzymes, catalase, 6-phospho-gluconic acid and glucose 6-phosphate dehydrogenase were uniformly distributed. Alkaline phosphatase was associated with extracellular vesicles found in hypertrophic cartilage. EM dense granules were found in mitochondria in hypertrophic cartilage. There was an increase of total lipids in hypertropic and calcified cartilage as compared to resting cartilage.

Alcian Blue↗
PubMed2000

Adhesive force of chondrocytes to cartilage. Effects of chondroitinase ABC.

Chondrocyte transplantation is a clinical procedure for cartilage repair. Transplanted cells may have difficulty attaching to the surface of chondral lesions because of the anti-adhesive properties of the proteoglycan rich matrix. This study used micromanipulation methods to determine if pretreatment of cartilage with chondroitinase ABC affects chondrocyte adhesion to cartilage and if chondrocytes adhere preferentially to the superficial, middle, or deep layers of cartilage. Bovine chondrocytes were transplanted in vitro on articular cartilage sections cut perpendicular to the articular surface. At various times between 15 and 75 minutes after seeding, a micropipette micromanipulation system was used to measure the adhesion force of individual chondrocytes to cartilage. The chondrocyte adhesion force increased with chondroitinase ABC treatment and seeding time but generally was similar for the different regions of articular cartilage (superficial, middle, deep layer) to which the cells were attached. For normal cartilage, the adhesion force increased from 1.29 +/- 0.24 mdyne after 15 to 30 minutes seeding to 5.29 +/- 0.25 mdyne after 60 to 75 minutes. Treatment with chondroitinase ABC at certain concentrations and durations (1.0 U/mL for 5 minutes or 0.5 or 1 U/mL for 15 minutes) led to an increase in adhesion force, whereas relatively low concentration or treatment time (0.25 U/mL for 15 minutes or 0.5 U/mL for 5 minutes) had little or no detectable effect. The increase in adhesion attributable to chondroitinase ABC treatment appeared most marked (+144% to +292%) for short (15 to 30 minutes) seeding durations but was still significant (+46%) for the longest seeding period (60 to 75 minutes) studied after the 1 U/mL for 15 minute treatment condition. These results provide direct biomechanical evidence that enzymatic treatment of a cartilage surface can enhance chondrocyte adhesion.

Analysis of Variance↗
PubMed1997

Three-dimensional computerized reconstruction. Illustration of incremental articular cartilage thinning.

RATIONALE AND OBJECTIVES: The authors have addressed the ability of magnetic resonance (MR) imaging to resolve incremental thinning of articular cartilage by assessment of three-dimensional (3-D) and two-dimensional (2-D) representations. METHODS: Using a porcine knee model, sequential cartilage shavings were characterized using a 3-D fat suppressed spoiled gradient-echo (SPGR) MR imaging protocol that provided good contrast between high-signal articular cartilage and lower signal surrounding tissues. Lesion dimensional measurements were made on both MR images and 3-D computerized reconstructions. Volumes of cartilage removed were approximately 0.06 mL. RESULTS: Incremental articular cartilage thinning typically was apparent on 3-D reconstructed images. Three-dimensional articular cartilage reconstructions were effective in depicting location and orientation of shaved cartilage regions. Average percent error associated with length and with measurements based on 2-D MR images was approximately 19% for observer 1 and 33% for observer 2 when compared with direct measurements of the shaved cartilage. Average percent error of thickness measurements based on 2-D MR was approximately 21% for observer 1 and 37% for observer 2. Overall average errors associated with length, width, and thickness measurements were approximately 25%. CONCLUSIONS: Incremental thinning of articular cartilage can be tracked qualitatively and quantitatively using 3-D computerized reconstructions and 2-D MR images. Errors associated with the quantitative measurements can be attributed to limitations of measurement methods and intrinsic limitation of MR resolution.

Animals↗
PubMed1998

Measurement of localized cartilage volume and thickness of human knee joints by computer analysis of three-dimensional magnetic resonance images.

RATIONALE AND OBJECTIVES: This work demonstrates a new method for computerized measurement of the dimensions (thickness and volume) of articular cartilage for any specified region of the human knee joint. Three-dimensional magnetic resonance (MR) images optimized for cartilage contrast have been analyzed using computerized edge-detection techniques, and the reproducibility of articular cartilage thickness and volume measurements is assessed. METHODS: A fat-suppressed, three-dimensional SPoiled GRass MR sequence (45/7.5/30 degrees) with total scan time of approximately 12 minutes was used to acquire volume images of human knee joints at spatial resolution of 0.6 x 1.2 x 1.2 mm. Measurements were made using six repeated scans for three healthy volunteers over a period of 2 months. The subsequent semi-automated image processing to establish total cartilage volume and cartilage thickness maps for the femur required approximately 60 minutes of operator time. RESULTS: The mean coefficient of variation for total cartilage volume for the six repeated scans for the three volunteers was 3.8%, and the average coefficient of variation for the user-selected cartilage plugs was 2.0%. The cartilage thickness maps from the repeated scans of the same knee were similar. CONCLUSIONS: Standard resolution MR images with fat-suppressed contrast lead to an objective and reproducible measurement of spatial dimensions of articular cartilage when analyzed semi-automatically using computerized edge-detection methods.

Adult↗
PubMed2002

Acoustic properties of different cartilage reconstruction techniques of the tympanic membrane.

OBJECTIVES/HYPOTHESIS: The use of cartilage in reconstruction of the tympanic membrane has been established especially in cases such as tubal dysfunction and adhesive processes. Cartilage offers the advantage of higher mechanical stability compared with membranous transplants but may alter the acoustic transfer characteristics of the graft. Apart from material properties, it can be assumed that, also, the microsurgical reconstruction technique might influence the sound transmission properties of the reconstructed tympanic membrane. The purpose of the study was to investigate the acoustic transfer characteristics of different cartilage transplants being typically used in different reconstruction techniques of the tympanic membrane. METHODS: Cartilage plates of different thicknesses (1.0, 0.7, 0.5, and 0.3 mm), cartilage palisades, and cartilage island transplants of varying size were investigated by means of an ear canal-tympanic membrane model. In contrast to former single-point measurements, sound-induced vibrational amplitudes of the entire transplant were measured by scanning laser Doppler vibrometry (measuring points, n = 133) (PSV-200, Polytec, Waldbronn, Germany). Frequency response functions (displacement vs. sound pressure) of all measured points were determined in the frequency range of 200 Hz to 4 kHz for the different transplants. RESULTS: Cutting thick cartilage transplants into thin plates or palisades decreased the first resonance frequency and increased its amplitude, reflecting improved sound transmission properties of the transplant. From an acoustical point of view, the 0.5-mm cartilage plate seems preferable compared with the palisade technique. Cartilage island techniques showed vibration characteristics superior to plate or palisade techniques. CONCLUSIONS: Apart from material characteristics, the sound transmission properties of the reconstructed tympanic membrane are strongly influenced by the reconstruction technique. The choice of the surgical technique should consider requirements based on mechanical stability and acoustic transfer characteristics of the transplant.

Acoustics↗
PubMed1999

Injectable tissue-engineered cartilage using a fibrin glue polymer.

The purpose of this study was to demonstrate the feasibility of using a fibrin glue polymer to produce injectable tissue-engineered cartilage and to determine the optimal fibrinogen and chondrocyte concentrations required to produce solid, homogeneous cartilage. The most favorable fibrinogen concentration was determined by measuring the rate of degradation of fibrin glue using varying concentrations of purified porcine fibrinogen. The fibrinogen was mixed with thrombin (50 U/cc in 40 mM calcium chloride) to produce fibrin glue. Swine chondrocytes were then suspended in the fibrinogen before the addition of thrombin. The chondrocyte/polymer constructs were injected into the subcutaneous tissue of nude mice using chondrocyte concentrations of 10, 25, and 40 million chondrocytes/cc of polymer (0.4-cc injections). At 6 and 12 weeks, the neocartilage was harvested and analyzed by histology, mass, glycosaminoglycan content, DNA content, and collagen type II content. Control groups consisted of nude mice injected with fibrin glue alone (without chondrocytes) and a separate group injected with chondrocytes suspended in saline only (40 million cells/cc in saline; 0.4-cc injections). The fibrinogen concentration with the most favorable rate of degradation was 80 mg/cc. Histologic analysis of the neocartilage showed solid, homogeneous cartilage when using 40 million chondrocytes/cc, both at 6 and 12 weeks. The 10 and 25 million chondrocytes/cc samples showed areas of cartilage separated by areas of remnant fibrin glue. The mass of the samples ranged from 0.07 to 0.12 g at 6 weeks and decreased only slightly by week 12. The glycosaminoglycan content ranged from 2.3 to 9.4 percent for all samples; normal cartilage controls had a content of 7.0 percent. DNA content ranged from 0.63 to 1.4 percent for all samples, with normal pig cartilage having a mean DNA content of 0.285 percent. The samples of fibrin glue alone produced no cartilage, and the chondrocytes alone produced neocartilage samples with a significantly smaller mass (0.47 g at 6 weeks and 0.46 g at 12 weeks) when compared with all samples produced from chondrocytes suspended in fibrin glue (p < 0.03). Gel electrophoreses demonstrated the presence of type II collagen in all sample groups. This study demonstrates that fibrin glue is a suitable polymer for the formation of injectable tissue-engineered cartilage in the nude mouse model. Forty million chondrocytes per cc yielded the best quality cartilage at 6 and 12 weeks when analyzed by histology and content of DNA, glycosaminoglycan, and type II collagen.

Animals↗