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.

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.

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.

A morphologic, biochemical, and biomechanical assessment of short-term effects of osteochondral autograft plug transfer in an animal model.

PURPOSE: The objective of this study was to assess the short-term changes that occur after an osteochondral autograft plug transfer from the femoral trochlea to the medial femoral condyle in a goat model. TYPE OF STUDY: Articular cartilage repair animal study. METHODS: Six adult male goats were used in this study. Two 4.5-mm osteochondral plugs were transferred from the superolateral femoral trochlea to 2 recipient sites in the central portion of the medial femoral condyle for a survival period of 12 weeks. Postmortem, the global effects of the procedure were assessed by gross morphologic inspection and by analyzing the synovial DNA for inflammatory response. The recipient sites were also evaluated histologically and biomechanically. Metabolic activity was determined by (35)SO(4) uptake, and viability was assessed using a live/dead stain and by confocal laser microscopy. RESULTS: There was no evidence of significant gross morphologic or histologic changes in the operative knee as a result of the osteochondral donor or recipient sites. The patella, tibial plateau, and medial meniscus did not show any increased degenerative changes as a result of articulating against the donor or recipient sites of the osteochondral autografts. Analysis of synovial DNA revealed no inflammatory response. Biomechanically, 6- to 7-fold greater stiffness was noted in the cartilage of the transferred plugs compared with the control medial femoral condyle. Furthermore, on histologic examination, the healing subchondral bone interface at the recipient site had increased density. Glycosaminoglycan synthesis as determined by (35)SO(4) uptake was upregulated in the transplanted cartilage plug relative to the contralateral control, showing a repair response at the site of implantation. And finally, confocal microscopy showed 95% viability of the transferred plugs in the medial femoral condyle region. CONCLUSIONS: Our findings demonstrate the ability to successfully transfer an osteochondral autograft plug with maintenance of chondrocyte cellular viability. The transferred cartilage is stiffer than the control medial femoral condyle cartilage, and there is concern regarding the increased trabecular mass in the healing subchondral plate, but these do not result in increased degenerative changes of the opposing articular surfaces in the short term.

The effects of hyaluronan on the meniscus in the anterior cruciate ligament-deficient knee.

Anterior cruciate ligament (ACL) deficiency often induces meniscal tears and, ultimately, degenerative joint disease. The hypothesis of this study was that hyaluronan (HA; MW = 8 x 105) may have a protective effect on the medial meniscus following a period of ACL deficiency. The animal model consisted of creating an ACL deficiency by ACL transection (ACLT) in 51 mature New Zealand white rabbits. Postoperative injections started 4 weeks after ACLT to allow the ACL deficiency to create a degenerative change in the meniscus. The first group (n = 26) was injected with HA and the second group (n = 25) was injected with vehicle (phosphate-buffered saline) in their ACL-deficient knees once a week for 5 weeks, in a protocol similar to that used clinically. At the end of the injections, the HA-treated menisci showed a reduced meniscus area histomorphometrically (P<0.01), as well as a decrease in water content (P<0.01) when compared with the vehicle-treated menisci. The matrix composition of the menisci was assessed by the total glycosaminoglycans (GAGs) content, which decreased in the vehicle-treated menisci (P<0.05) but did not decrease in the HA-treated menisci. In our model, a positive effect of HA was observed biochemically on the preservation of the meniscus matrix composition in the ACL-deficient knee.

Long-term effect of sodium hyaluronate (Hyalgan) on osteoarthritis progression in a rabbit model.

BACKGROUND: Intra-articular (IA) hyaluronan (HA) injections are approved for the treatment of knee osteoarthritis (OA) pain. One of the currently available products is approved for repeat treatment courses. While HA is classed as a symptom-modifying agent, there is substantial evidence that this therapeutic modality also possesses disease-modifying activity. OBJECTIVE: A rabbit model of OA, anterior cruciate ligament transection (ACLT), was used to investigate the long-term effects of single and sequential courses of HA therapy on OA progression. DESIGN: One or two courses of five weekly IA injections of sodium hyaluronate (Hyalgan) average molecular weight, MW, of 500-730 kDa, or vehicle were administered to rabbits (N=10 per group), initiated 4 and 13 weeks (for groups that received a second course) after ACLT. Gross morphological and histomorphometric evaluations were performed on harvested knee joints following sacrifice at 26 weeks after surgery. RESULTS: All the rabbits exhibited the characteristic pathologic changes of OA. Rabbits that received one or two courses of HA injections showed less disease progression than rabbits treated with ACLT alone or with 10 vehicle injections. However, rabbits that received five vehicle injections also showed improved morphology compared with those given no injections. Rabbits that received 10 HA injections showed significantly less surface roughness of the femoral cartilage compared with rabbits treated with ACLT, 5 HA injections, or 10 vehicle injections, and showed significantly less surface roughness of the tibial plateau compared with all other treatment groups (P<0.05). CONCLUSIONS: Repeat courses of HA injections reduced the degree of articular degeneration in a rabbit ACLT model of OA. Sequential courses of HA therapy may be advantageous in the long-term management of OA.