The biomechanical changes in rabbit knee contractures were measured after 9 weeks of immobilization. These results were correlated with the biochemical composition of periarticular connective knee tissue of the same knees. The loss of total hexosamine correlates significantly with joint stiffness on an animal-to-animal basis. Total hexosamine also correlates with the energy required cyclicly to flex and to extend the experimental joints. Of the individual glycosaminoglycan fractions, only hyaluronic acid showed significant correlation with the biomechanical data. The possible mechanism of contracture formation was postulated based on these results.

Animals↗

PubMedDate not supplied

Experimental hemarthrosis in the knee of the mature canine.

The knee joints of 14 skeletally mature mongrel dogs were subjected to a continuous hemarthrosis. Minimal morphologic changes of the articular cartilage did not occur until after 16 weeks. As early as 4 weeks, biochemical analyses showed a significant decrease in glycosaminoglycans (GAG) that became progressively more severe with time, whereas total collagen was not significantly altered until after 12 and 16 weeks. Bioengineering measurements of the experimental cartilage surfaces showed that the tissue becomes more deformable as well as less resistive to shear than the control at 8 weeks. These differences increased as the duration of hemarthrosis increased.

Animals↗

PubMedDate not supplied

Regulation of alpha(v)beta3 and alpha5beta1 integrin receptors by basic fibroblast growth factor and platelet-derived growth factor-BB in intrasynovial flexor tendon cells.

Integrins are important players in soft tissue healing as molecules that mediate communication between cells and extracellular matrix. Thus, the regulation of the expression of these molecules would be important during wound repair. To explore the regulatory roles of specific growth factors on integrin expression by intrasynovial flexor tendon cells, the present study assessed the in vitro effects of basic fibroblast growth factor and platelet derived growth factor-BB on expression of the alpha5beta1 and alpha(v)beta3 integrins in these cells. Analyses were carried out at the transcriptional (reverse transcription-polymerase chain reaction) and translational (immunohistochemistry) levels of cellular metabolism. Both types of analyses revealed increased expression of alpha5beta1 and alpha(v)beta3 by tendon cells exposed to either basic fibroblast growth factor or platelet-derived growth factor-BB over a wide range of growth factor concentrations employed in the study. Semiquantitative reverse transcription-polymerase chain reaction showed that, relative to control, basic fibroblast growth factor and platelet-derived growth factor-BB increased the expression of alpha(v) mRNA by 2-and 3-fold, respectively. Alpha 5 mRNA expression was also increased 3-fold by basic fibroblast growth factor, and 2-fold by platelet-derived growth factor-BB. We believe the results of this study are significant because the specific integrins affected are intimately involved in two events that have been shown to be important to intrasynovial flexor tendon healing, namely fibronectin deposition (alpha5beta1) as part of the provisional matrix and angiogenesis/revascularization (alpha(v)beta3).

Animals↗

PubMedDate not supplied

The effects of hyaluronan on tissue healing after meniscus injury and repair in a rabbit model.

To assess the effect of hyaluronan on meniscus injury and repair, we had 35 mature New Zealand White rabbits undergo bilateral meniscus injury and repair (19 in the peripheral region, and 16 in the inner region). A longitudinal tear was created in the medial meniscus and repaired with horizontally placed nylon sutures. The left knee joint received intraarticular injections of hyaluronan 1 week after surgery and once a week for 5 weeks. The right knees were injected with phosphate-buffered saline (the carrier vehicle of the hyaluronan). Twelve weeks after repair, tears in the peripheral region showed gross and histologic evidence of healing, with no difference between the vehicle- and hyaluronan-treated menisci. Biochemically, the ratio of reducible collagen cross-links in the hyaluronan-treated menisci was significantly higher than in the vehicle-treated menisci, indicating greater level of collagen remodeling. Biomechanically the vehicle- and hyaluronan-treated menisci demonstrated similarly high tearing load and fracture toughness. In the inner region, poor healing response was observed grossly and histologically in both treatment groups. Water content in the hyaluronan-treated menisci was significantly lower than in the vehicle-treated menisci, indicating a lower level of swelling. Hyaluronan treatment stimulated collagen remodeling in the peripheral region and inhibited swelling of the meniscus repaired in the inner region.

Adjuvants, Immunologic↗

PubMedDate not supplied

Matrix assessment of the articular cartilage surface after chondroplasty with the holmium:yttrium-aluminum-garnet laser. A long-term study.

A long-term in vivo study was performed to assess biochemical changes after laser repair of articular cartilage. Forty New Zealand White rabbits were sacrificed 26 weeks after undergoing an articular cartilage chondroplasty with use of a holmium:yttrium-aluminum-garnet laser at 0.8 joules per pulse and a rate of 10 Hz. Glycosaminoglycan content in the repaired tissue decreased significantly with both perpendicular (19.59+/-5.6 microg hexosamin/mg of dry tissue) and tangential delivery (14.78+/-4.5 microg/mg) compared with the sham-treated tissue (39.6+/-5.0 microg/mg). Cellular viability was also significantly decreased. Sulfate incorporation was decreased to 203+/-142 cpm/mg of dry cartilage in the tangential mode and 461+/-209 cpm/mg in the tangential mode, compared with the sham at 1845 cpm/mg. Uptake of [3H]thymidine decreased to 463+/-473 cpm/mg of dry tissue and 455+/-170 cpm/mg in the tangential and perpendicular modes, respectively, compared with 2465 cpm/mg in the sham tissue. There were no significant differences between the tangential and perpendicular delivery modes in any assessments performed. The shortterm chondrocyte destruction previously noted in a 12-week study after laser treatment was not reversed during a longer-term 26-week study, and cellular viability was not recovered, suggesting that the loss of chondrocyte function may be permanent.

Aluminum Silicates↗

PubMedDate not supplied

Medial collateral ligament healing. A multidisciplinary assessment in rabbits.

Medial collateral ligament healing without treatment has been studied in a rabbit model. Complete midsubstance gaps were found to heal by distinct scar formation over time. This healing process was fast since the gap was bridged quickly; however, more subtle changes in appearance of the healing tissue continued for many months. The ligament "scar" was found to be structurally abnormal chemically and mechanically even at long-term followup. A plateau in its improvement suggests that the scar may never approach normal ligament characteristics (without treatment). A baseline of ligament healing by scar formation has been established.

Animals↗

PubMedDate not supplied

The natural history of the anterior cruciate ligament autograft of patellar tendon origin.

A rabbit model for ACL reconstruction using autogenous patellar tendon (PT) was used to study graft viability, its response to new physical forces, and the intrasynovial milieu. The autograft was assessed grossly, histologically, and biochemically with respect to time. Histologic observations demonstrated that autografts were centrally acellular with a peripheral rim of cells at 2 weeks, and had a central focal proliferation of cells at 3 weeks and cellular homogeneity by 4 weeks postoperation. Necrosis followed by cellular proliferation suggested that a population of cells other than the native PT fibroblasts may be inhabiting the graft. Graft sequestration experiments demonstrated that autografts are repopulated by cells of extrinsic origin after transplantation. Autografts showed a gradual assumption of the microscopic properties of normal ACL; by 30 weeks posttransplant the tissue characteristics were ligamentous in appearance. Histologic changes paralleled the biochemical metamorphosis: Type III collagen was not observed in PT; however, a gradual increase in its concentration was seen in the grafts; by 30 weeks its concentration (10%) was the same as in normal ACL. Similarly, glycosaminoglycan content increased from its normally low level in PT to that found in native ACL. Collagen-reducible cross-link analysis revealed that grafted tissue changed from the normal PT pattern of low dihydroxylysinonorleucine and high histidinohydroxymerodesmosine to the opposite pattern seen in normal ACL by 30 weeks. These data suggest that PT autografts undergo a process of "ligamentization" when placed in the ACL environment, and that cells responsible for this metamorphosis are of extragraft origin.

Adaptation, Physiological↗

PubMedDate not supplied

The effects of increased tension on healing medical collateral ligaments.

The effects of motion and increased levels of stress on the biomechanical, biochemical, and morphological properties of healing medial collateral ligaments were assessed in a rabbit model. In one group, the medial collateral ligament of the left hindlimb was transected and allowed to heal with cage activity for either 6 or 12 weeks. In another group, the transected ligaments were permitted to heal for 4 weeks and then were placed under increased stress by inserting a stainless steel pin perpendicularly underneath the healing medial collateral ligament. The animals were allowed cage activity for an additional 2 or 8 weeks. The varus-valgus joint laxity and the stress-strain properties of the medical collateral ligament substance were obtained. Further, the quantity of total collagen, amount and ratio of the collagen cross-links, dihydroxylysinonorleucine and hydroxylysinonorleucine, and the histologic appearance of the healing medical collateral ligaments were evaluated for all groups. At 6 weeks, knees with a transected medial collateral ligament were twice as lax as the controls. However, joints with the stainless steel tension pin had varus-valgus values approximately 1.5 times those of the controls. At 12 weeks, joints with increased stress were not statistically different from the controls. The group that had healing with increased stress for 12 weeks produced the highest stress for a given strain compared to any other group. Also, the total collagen levels and the ratio of dihydroxylysinonorleucine/hydroxylysinonorleucine were the closest to normal of any transected group. Finally, qualitative histologic improvements were seen, including a more longitudinal arrangement of collagen fibers and decreased cellularity.

Animals↗

PubMedDate not supplied

Matrix assessment of the articular cartilage surface after chondroplasty with the holmium:YAG laser.

The goal of this study was to evaluate, histologically and biochemically, repair of the articular cartilage in a rabbit joint after the use of the holmium:yttrium-aluminum-garnet laser in a cartilage chondroplasty model. In 30 New Zealand White rabbits, chondroplasty was performed with the laser at an intensity of 0.8 J at a rate of 10 Hz. The animals were sacrificed 12 weeks after surgery. Histologically, the safranin O staining index of proteoglycan correlated well with the biochemical results, illustrating a decrease of proteoglycan in the repaired articular cartilage after laser articular cartilage chondroplasty. The damaged articular cartilage surface after the laser application was extensive. The damaged area observed was gradually distributed along the radius from the central point of the laser beam application. Biochemically, the amount of glycosaminoglycan in the repaired tissue (8 +/- 2 mg of hexosamine per gram of dry cartilage) was statistically less when compared with that in the sham-treated tissue (40 +/- 5 mg). The amount of sulfate incorporated into proteoglycans was 8 to 10 times less in the chondroplasty model compared with the control, suggesting that cell viability was greatly reduced in the treated tissues or expression of proteoglycans was greatly reduced. In the subchondral area, histologic evaluation showed the lack of osteocytes in lacunae of the bone tissue after use of laser energy. The architecture of the subchondral bone in the chondroplasty area was damaged, with damage also seen in the membranes of the blood vessels.

Aluminum Silicates↗

PubMedDate not supplied

The effects of hyaluronan on the meniscus and on the articular cartilage after partial meniscectomy.

The effect of hyaluronan (molecular weight = 8 x 10(5)) on the meniscus and on the articular cartilage was assessed after partial meniscectomy in a rabbit model. On gross examination, remodeled meniscus appeared as newly synthesized translucent tissue, and was seen in both vehicle- and hyaluronan-treated menisci. Histologically, safranin O staining revealed the strong presence of glycosaminoglycans in the newly remodeled tissue, and polarized light demonstrated the absence of mature collagen architecture. Hydration of the hyaluronan-treated menisci was significantly less than that of the vehicle-treated menisci, and the reducible collagen cross-link dihydroxylysinonorleucine was significantly increased in the hyaluronan-treated menisci compared with the vehicle-treated menisci, indicative of a greater degree of collagen remodeling. In situ hybridization of vehicle- and hyaluronan-treated menisci revealed a high level of type I procollagen mRNA expression and minor expressions of types II and III mRNA. Expression of the type I collagen gene appeared to be more pronounced in the hyaluronan-treated menisci than in the vehicle-treated menisci. The tibial plateaus revealed mild cartilage fibrillation after partial meniscectomy. A statistically significant difference between vehicle- and hyaluronan-treated cartilage was not demonstrated in the present study because of the slow development (i.e., 12 weeks) of osteoarthritis after partial meniscectomy in the rabbit model. These results suggest that in the rabbit model, hyaluronan enhances collagen remodeling and inhibits meniscal swelling after partial meniscectomy in the avascular region.

Analysis of Variance↗

PubMedDate not supplied

The connective-tissue response to immobility: a study of the chondroitin-4 and 6-sulfate and dermatan sulfate changes in periarticular connective tissue of control and immobilized knees of dogs.

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Animals↗

PubMedDate not supplied

Effect of salicylate therapy on cartilage destruction in experimental pyarthrosis.

An experimental rabbit pyarthrosis model was utilized to investigate the effects of sodium salicylate therapy on cartilage destruction. Animals were innoculated with 10(3) organisms of Staphylococcus aureus 502A. The opposite knee was injected with sterile saline. Infection was documented 48 hours post innoculation, procaine penicillin therapy initiated, and the adequacy of therapy evaluated at sacrifice. One half of the animals began salicylate feedings one week prior to injection and this continued until sacrifice at 14 or 49 days. Salicylate levels were 12.5 +/- 6.9 mg %. There was a significant loss of cartilage in both the salicylate treated and untreated animals. The levels of salicylate obtained in this study were not protective to cartilage in a septic joint.

Animals↗

PubMedDate not supplied

Stress deprivation effect on metabolic turnover of the medial collateral ligament collagen. A comparison between nine- and 12-week immobilization.

The effects of intermediate-term immobilization on the medial collateral ligament (MCL) of the rabbit knee are profound. Immobilization causes atrophy with reduction of collagen mass and increased collagen degradation in th immobilized MCL. The matrix composition, as reflected by collagen turnover, changed dramatically as the period of immobilization was increased from nine to 12 weeks. Collagen degradation during these three additional weeks increases, as demonstrated by the fact that at 12 weeks, collagen degradation is 28% higher than that in controls, compared with 14% at nine weeks. Degradation, balanced by new collagen synthesis, produced very minor net decrease in total collagen mass (-2%) after nine weeks, but a large decrease in total collagen mass (-27%) is observed at the end of 12 weeks. Exponential degradation has occurred as immobilization has continued, and ligament regenerative capacity apparently has failed.

Animals↗