Tissue toxicity of antiseptic solutions. A study of rabbit articular and periarticular tissues

The gross, histologic, and biochemical effects of four commercially available antiseptic solutions on rabbit knee articular and periarticular connective tissues were investigated. Rabbit knee joints were injected with 2.0 cc of either Betadine prep solution, Betadine scrub solution, pHisohex or 3% hexachlorophene. The opposite knees were injected with sterile saline. All animals were injected three times at 48-hour intervals and sacrificed 10 days after the last injection. The solutions containing detergents, Betadine scrub, and pHisohex caused severe gross and histologic damage to articular cartilage, synovia, and muscle. The hexachlorophene loss solution caused moderate histologic damage, but caused articular cartilage ground substance. Betadine prep solution caused only minimal gross and histologic damage, without any biochemical evidence of articular cartilage damage. If antiseptic solutions are to be used in irrigating or packing joint injuries, the use of Betadine prep is recommended.     

Articular cartilage lesions of the knee

The pathogenesis and clinical significance of articular cartilage lesions of the knee persist as topics of considerable interest among orthopedic surgeons. This study was designed to assess the association of articular cartilage degeneration with concomitant intraarticular abnormalities and to correlate the prevalence and severity of articular cartilage damage with preoperative historical and physical exam findings in patients presenting with knee pain. Twenty-six history and physical exam data points were prospectively collected from 192 patients (200 knees), consecutively undergoing arthroscopic knee surgery. During surgery, all articular cartilage lesions were recorded with respect to size, location, and character and were graded according to Oglivie-Harris et al. All concomitant knee joint abnormalities were simultaneously recorded. Of 200 knees examined arthroscopically, 12 knees revealed no demonstrable etiology for the presenting symptoms, 65 knees revealed assorted intraarticular pathology but no articular cartilage degeneration, and the remaining 123 knees revealed a total of 211 articular cartilage lesions (103 femoral, 72 patellar, 36 tibial); 7 femoral, 6 patellar and 0 tibial lesions were completely isolated (no concomitant knee joint pathology). The concomitance of femoral defects with tibial lesions was highly significant (p = 0.01). Femoral and tibial articular cartilage lesions were strikingly correlated with the presence of an unstable torn meniscus (p less than 0.001). Medial compartment articular cartilage lesions were significantly more common (p = 0.001), more closely associated with meniscal derangement, and appreciably more severe than lateral compartment lesions. In 75% of anterior cruciate ligament-deficient knees with concomitant articular cartilage degeneration, the duration from injury to surgery was greater than 9 months, and in each of these cases, a history of reinjury to the knee was elicited. From these data one can conclude that: (a) in some patients with painful knees, isolated articular cartilage lesions may be the only abnormality noted at arthroscopy; (b) unstable meniscal tears are significantly associated with destruction of articular cartilage; (c) the medial compartment is particularly susceptible to articular cartilage degeneration; and (d) in our series, anterior cruciate ligament tears were increasingly associated with articular cartilage destruction as the elapsed time from injury to arthroscopy increased.     

Acute effect of open joint wounds on articular cartilage and synovium in rabbits

Open joint wounds were made in immature and mature rabbit knees by surgical arthrotomy. The wounds of the right knees were packed open for 5 days and the left knee wounds were closed primarily. The biochemical studies were selected to determine the effect of our treatment regimen on changes in the metabolism of articular cartilage and synovium. Neither closed nor open treatment produced significant changes in enzyme activities measured in the articular cartilage as compared to the controls in either immature or mature rabbits. Most of the synovial enzymes were elevated in the injured joints. There were, however, no significant differences in enzyme activity between the joints treated by either open or closed methods. Our findings suggest that short-term open treatment wounds does not cause matrix degradation in the cartilage nor affect the synovium more than simple arthrotomy.     

Effects of low-intensity pulsed ultrasound in repairing injured articular cartilage

Articularcartilageisakindofavascularmusculoskeletaltissueswitharelativelylowcapacityforintrinsicrepairorregeneration.Intheabsenceofavailablestemcells,thereislittlehopeforcartilagerepairafterinjuryandthetissuesprogress alongadegenerativepathwaythatdestroysthe biochemicalandbiomechanicalproperties.Sorepairof damagedarticularcartilageisoneofthemostdifficult problemsinorthopaedicsandnosatisfactorytreatment methodhasbeenfoundinthisfield.Ultrasoundhas beenwidelyusedinclinicaldiagnosisandtreatment.It…     

The use of intra-articular Na-hyaluronate as a potential chondroprotective device in experimentally induced acute articular cartilage injury and repair in rabbits.

OBJECTIVE: This study examined if viscosupplementation from intra-articular administration of a commercially available form of hyaluronan (HA) could promote the restoration of proteoglycan (PG) depletion induced by chymopapain and then if the repair could be maintained once HA treatment was discontinued. METHODS: Animals received cartilage injury with intra-articular chymopapain (2.0 mg) followed by weekly treatment with intra-articular HA. HA treated animals were compared to injured animals with no treatment, contralateral untreated joints and joints from normal controls. The effect of intra-articular HA alone on articular cartilage was also examined. RESULTS: Serum keratan sulfate levels confirmed degradation of the cartilage PGs in the chymopapain-injected knees. Intra-articular chymopapain resulted in marked loss of PGs. There were no significant differences among the control groups (untreated control, HA/800 treatment only). HA treatment did not affect the loss of PGs caused by chymopapain after 42 days. However, in animals receiving chymopapain injury followed by weekly HA treatment for 42 days and then 42 days of free cage activity without HA, cartilage PG contents were significantly increased. Intra-articular HA alone had no effect on the articular cartilage. CONCLUSION: The results in the present study suggest a potential protective effect of HA on chymopapain-induced acute articular cartilage injury in rabbits that, in time, permits damaged cartilage to resynthesize matrix PGs after the HA treatment is discontinued.     

The effect of hyaluronic acid on cartilage in the immobilized rabbit knee

Out of 30 adult rabbits, 20 had one knee immobilized with a plaster of Paris cast for 6 or 12 weeks, and 10 rabbits were used as untreated controls. Prior to immobilization, 10 knees were injected with high-molecular weight hyaluronic acid. The articular cartilage of the femoral condyles was studied by light microscopy, whereas that of the patella and tibia was analyzed biochemically. Degenerative changes of the articular cartilage similar to those seen in arthrosis were observed after 6 weeks. The intraarticular injection of hyaluronic acid did not prevent these changes; instead, the reparative processes seemed inhibited.     

Reconstruction of patellar cartilage defects with free periosteal grafts. An experimental study

The osteo-chondrogenic potential of free periosteal grafts was investigated within the knee joint in 26 rabbits aged four to six weeks. A total of 36 knee joints were operated on. The grafts were stripped from the medial side of the right tibia and sutured on the articular surface of the patella, from which the cartilage had been totally excised to the subchondral bone. In 16 knees the graft was sutured with the cambium layer towards the subchondral bone and in eight knees the fibrous layer faced the bone. In the control group of twelve knees the patellar articular cartilages were excised and no periosteal transplant was grafted to the patellar articular surface. In the transplantation group cartilage formation could be seen already one week after the operation. There were no marked differences between the series with the cambium layer facing the subchondral bone or the group with the fibrous layer facing the bone. At 20 weeks the hypertrophied cartilage had thinned and resembled normal joint cartilage. In the control group the histological picture resembled osteoarthritis.     

One intra‐articular injection of hyaluronan prevents cell death and improves cell metabolism in a model of injured articular cartilage in the rabbit

The purpose of this study was to determine the effect of one intra‐articular injection of hyaluronan on chondrocyte death and metabolism in injured cartilage. Twenty‐three 6‐month‐old rabbits received partial‐thickness articular cartilage defects created on each medial femoral condyle. In order to examine the effect on articular cartilage surrounding iatrogenic cartilage lesions, which can occur during arthroscopic procedures, Study 1 was performed: in 14 rabbits both knees were immediately rinsed with 0.9% NaCl. Experimental knees were treated with hyaluronan. Six rabbits were sacrificed at 2 days; eight rabbits 3 months postoperatively. Histomorphometric analysis was used for studying cell death in cartilage next to the defect. In order to examine the effect on longer lasting lesions, more reflecting the clinical situation, Study 2 was performed: after 6 months knee joints of nine rabbits were (i) irrigated with 0.9% NaCl, (ii) treated with hyaluronan after irrigation with 0.9% NaCl, or (iii) sham‐treated. After 7 days patellas were used to study the chondrocyte metabolism by measuring the [³⁵S]sulfate incorporation. Study 1: Two days postoperatively, in hyaluronan‐treated cartilage the percentage of dead cells was 6.7%, which was significantly lower compared to 16.2% in saline‐treated cartilage. After 3 months the percentages of dead cells in both groups were statistically similar. Study 2: Hyaluronan treatment resulted in significantly higher [³⁵S]sulfate incorporation compared to knees irrigated with 0.9% NaCl. These results suggest a potential role for hyaluronan in preventing cell death following articular cartilage injury. One injection of hyaluronan improved cartilage metabolism in knees with 6‐month‐old cartilage defects. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:624–630, 2008     

Rabbit articular cartilage defects treated by allogenic chondrocyte transplantation

Articular cartilage defects have a poor capacity for repair. Most of the current treatment options result in the formation of fibro-cartilage, which is functionally inferior to normal hyaline articular cartilage. We studied the effectiveness of allogenic chondrocyte transplantation for focal articular cartilage defects in rabbits. Chondrocytes were cultured in vitro from cartilage harvested from the knee joints of a New Zealand White rabbit. A 3 mm defect was created in the articular cartilage of both knees in other rabbits. The cultured allogenic chondrocytes were transplanted into the defect in the right knees and closed with a periosteal flap, while the defects in the left knees served as controls and were closed with a periosteal flap alone, without chondrocytes. Healing of the defects was assessed at 12 weeks by histological studies. Allogenic chondrocyte transplantation significantly increased the amount of newly formed repair tissue (P=0.04) compared with that found in the control knees. The histological quality score of the repair tissue was significantly better (P=0.05), with more hyaline characteristics in the knees treated with allogenic chondrocytes than in the control knees. Articular cartilage defects treated with allogenic chondrocyte transplantation result in better repair tissue formation with hyaline characteristics than those in control knees.     

The effect of hyaluronic acid on cartilage in the immobilized rabbit knee

Out of 30 adult rabbits, 20 had one knee immobilized with a plaster of Paris cast for 6 or 12 weeks, and 10 rabbits were used as untreated controls. Prior to immobilization, 10 knees were injected with high-molecular weight hyaluronic acid. The articular cartilage of the femoral condyles was studied by light microscopy, whereas that of the patella and tibia was analyzed biochemically. Degenerative changes of the articular cartilage similar to those seen in arthrosis were observed after 6 weeks. The intraarticular injection of hyaluronic acid did not prevent these changes; instead, the reparative processes seemed inhibited.     

Treatment of antigen-induced arthritis in rabbits with dysprosium-165-ferric hydroxide macroaggregates

Dysprosium-165-ferric hydroxide macroaggregates (165Dy-FHMA) was used as an agent of radiation synovectomy in an antigen-induced arthritis model in New Zealand white rabbits. Animals were killed up to 6 months after treatment. 165Dy-FHMA was found to have a potent but temporary antiinflammatory effect on synovium for up to 3 months after treatment. Treated knees also showed significant preservation of articular cartilage architecture and proteoglycan content compared with untreated controls, but only during the first 3 months after treatment. In animals killed 3 and 6 months after treatment there were only minimal differences between the treated and untreated knees, indicating that the antiinflammatory effects on synovial tissue and articular cartilage preservation were not sustained.     

Chondral and osteochondral injuries associated with acute patellar dislocation

Purpose: The purpose of this study was to evaluate the frequency and precise pathology of articular cartilage injuries after acute patellar dislocation. Type of Study: Case series. Methods: In 39 consecutive knees with initial lateral patellar dislocation, the articular cartilage injuries were examined using arthroscopy or macroscopic observation. Results: Thirty-seven knees (95%) had articular cartilage injuries of the patellofemoral joint and 2 knees (5%) had no cartilage injury. In all 37 knees (95%), articular cartilage injuries were observed in the patella. The appearances were categorized into 3 groups: cracks alone (9 knees), cartilage defect caused by osteochondral or chondral fracture (7 knees), and cartilage defects caused by osteochondral or chondral fracture associated with cracks (21 knees). The main site of osteochondral fracture was the medial facet, and the main site of cracks was the central dome. Twelve knees (31%) had cartilage injury of the lateral femoral condyle. Conclusions: From this study, articular cartilage injuries, especially of the patella, seem to be common occurrences after acute patellar dislocation. Chondral and osteochondral injuries of the patella were classified into 3 groups.     

The torn or degenerated meniscus and its relationship to degeneration of the weight-bearing areas of the femur and tibia

Data was collected on 300 cadaver knees dissected for the prime purpose of studying chondromalacia of the patella. Simultaneous observations were also made on the state of the meniscus and the articular cartilage in the tibio-femoral joint. The data did not seem to support the oft-repeated statement that the torn meniscus is the primary cause of unicompartmental osteoarthritis. Investigations were also carried out on 69 additional cadaver knees and 100 consecutive unselected arthroscoped knees in which there was damage either to the meniscus or the adjacent joint surfaces. In 60% of the combined series of cadaver and arthroscoped knees, the meniscal changes could not be correlated with the condition of the articular cartilage. In the remaining 40% in which there was coexisting pathology in the meniscus and the articular cartilage, a cause and effect relationship could not be established, but there was no evidence that a torn meniscus posed a significant threat to the articular cartilage.     

Fibroblast growth factor 2 in synovial fluid from an osteoarthritic knee with cartilage regeneration

 The levels of fibroblast growth factor 2 (FGF2) in synovial fluid of osteoarthritic knees were measured. The correlation between FGF2 and the severity of cartilage degeneration in varus-deformed knees with medial compartmental osteoarthritis or the articular cartilage regeneration that occurs after high tibial osteotomy (HTO) were investigated. Knees that underwent total knee arthroplasty (TKA) were categorized as either mildly or severely degenerated according to a modified Outerbridge's grading system for degeneration of articular cartilage. Regeneration of articular cartilage was observed in a biopsy specimen from the medial femoral condyle removed with the patient's consent during hardware removal approximately 2 years after HTO. The joint fluid FGF2 level was measured at that time using an enzyme-linked immunosorbent assay. Cartilage regeneration was classified as immature or mature according to the staging for regeneration of articular cartilage. The histological findings were analyzed using Pineda's evaluation method for cartilage regeneration. The mean concentration of FGF2 was 57.4 ± 17.6 pg/ml in the joint fluid from knees with severely degenerated cartilage. This was higher than the FGF2 concentration found in the mildly degenerated group. Approximately 2 years after HTO the FGF2 level in synovial fluid was lower in knees with mature regenerated cartilage than in those with immature regeneration. Osteoarthritic knees at a more mature regeneration stage had a lower Pineda's histological score. This result suggested that the FGF2 concentration in knees with osteoarthritis was influenced by articular cartilage degeneration and regeneration, and it correlated with the histological evaluation. Received: September 26, 2002 / Accepted: January 20, 2003 RID="*" ID="*" Offprint requests to: K. Orito     

Porcine small intestine submucosa for repair of goat meniscal defects

This study evaluated the effectiveness of small intestine submucosa used as a graft to fill surgically created meniscal defects in a large animal model. Four goats underwent unilateral interior subtotal meniscectomies (approximately 70%) within the avascular portion of the medial meniscus. The contralateral meniscus acted as a control. Grafts of porcine small intestine submucosa were trimmed to fill the resected defects and sutured into place. After surgery the operated knees were casted in partial flexion to limit weight bearing on the affected limb. All of the animals were sacrificed at 12 weeks at which point meniscal regeneration and articular cartilage degradation were evaluated by gross and histologic examination. Grossly, the defects in the small intestine submucosa-grafted goats were partially filled with meniscal-appearing connective tissue. Histologically, the replacement tissue was typified by the presence of dense, cellular, irregularly organized connective tissue. Evaluation of the articular cartilage displayed increased degeneration in the grafted compartment of the operative knees. Each of the operative menisci partially regenerated. The grafts were conducive to repopulation with host meniscal elements. Despite partial meniscal regeneration, comparatively more articular cartilage degeneration in the treated knees was observed than in the untreated contralateral controls.     

Intra‐articular injections of bone morphogenetic protein‐7 retard progression of existing cartilage degeneration

We investigated the effect of weekly intra‐articular injections of bone morphogenetic protein‐7 (BMP‐7) on prevention of progression of existing cartilage degeneration in an osteoarthritis model in rabbits. An anterior cruciate ligament transection (ACLT) model was used to create a progressive osteoarthritis model. BMP‐7 was intra‐articular injected weekly into the right knee and PBS into the left knee from 4 weeks after ACLT. Both sides of the knees were compared macroscopically, histologically, immunohistochemically, and by micro CT. Macroscopically, fibrillation in the femoral condyle was observed 4 weeks after ACLT. In the control knees, cartilage degeneration further progressed throughout the 12‐week period. In the BMP‐7 treated knee, osteoarthritis progression was milder than in the control knees. Histologically, safranin‐O staining was decreased in the surgical knees at 4 weeks. Obvious erosions in both medial and lateral condyles were revealed in the control knees at 12 weeks, while cartilage matrix was predominantly retained in the BMP‐7 treated knees. The macroscopic and microscopic OA score in the BMP‐7 treated knee was better than that in the control in each rabbit. Immunohistochemical analysis demonstrated that both type II collagen and BMP‐7 were more expressed in cartilage treated with BMP‐7. Micro CT analysis showed that osteophytes were smaller in the BMP‐7 treated knee compared to that of the control. Weekly intra‐articular injections of BMP‐7 inhibited progression of existing cartilage degeneration. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1502–1506, 2010     

Osteoarthritis of the Knee in the Rabbit Produced by Immobilization:: Attempts to Achieve a Reproducible Model for Studies on Pathogenesis and Therapy

In order to obtain a reproducible experimental model of osteoarthritis a method of immobilizing the rabbit's knee in extension by means of a plastic splint was developed. The right knees of the rabbits were immobilized for periods varying from 4 days to 24 weeks. With the left knees as controls the knees were studied in a variety of ways among these being radiography (126 rabbits), histological sections stained with Alcian Blue (88 rabbits), analysis of ³⁵S-sulphate uptake (22 rabbits) and ³⁵S-autoradiography (6 rabbits). In 27 rabbits the regaining of mobility after immobilization was studied. After 5-6 weeks of immobilization most of the knees showed moderate or severe changes including loss of articular cartilage and osteophyte formation. Immobilization of the rabbit's knee by this method provokes a fairly easily reproducible type of degenerative joint disease showing similarities to advanced osteoarthritis as seen in humans.     

Irrigating solutions used in arthroscopy and their effect on articular cartilage. An in vivo study

The effect of arthroscopic irrigating solutions on articular cartilage was determined by the use of an animal model. Rabbit knee joints were irrigated continuously for two hours with either normal saline, Ringer's lactate, or sterile water. Subsequently, the rate of incorporation of 35SO4 by articular cartilage was used to measure the effect of the irrigants on chondrocyte metabolism. In addition, the irrigated groups were compared to an unirrigated control group. There was no significant difference in 35SO4 incorporation between the groups. This suggested that none of the irrigating solutions used in this study adversely affected articular cartilage function. On the basis of these findings, it appears that normal saline, Ringer's lactate, and sterile water can be safely used as irrigating solutions during most arthroscopic procedures.     

The effect of cryopreservation on the biomechanical behavior of bovine articular cartilage

The short-term effect of cryopreservation on specific mechanical behaviors of bovine articular cartilage has been investigated. A flat-ended nonporous indentor was used in a nondestructive, repetitive, axisymmetric unconstrained testing system. Cyclical indentation from a fixed position to a fixed load was applied until a steady-state load-deformation relationship (limit cycle) was achieved. Indentation behaviors measured from the limit cycles of each articular cartilage specimen before and after treatment were compared. Testing was done in vitro using fresh, mature bovine radiocarpal joints. Twenty pairs of cartilage-subchondral bone cores from anatomically similar sites on contralateral joints were separated into three groups; thickness controls, dimethylsulfoxide (DMSO) controls, and cryopreserved experimental samples. Thickness controls and DMSO controls were used to examine the isolated effects of the thickness measurement and DMSO incubation techniques on articular cartilage indentation characteristics. Experimental samples were cryopreserved using DMSO, their thicknesses similarly measured and indentation behaviors examined. Following testing, histological and histochemical assessment of the specimens confirmed the nondestructive nature of the tests. Intra- and intergroup comparisons of controls and experimentals revealed no statistical differences in the mechanical behaviors measured from the limit cycle or in cartilage thickness. These results indicate that the cryopreservation protocol used did not have an effect that we could measure on these specific mechanical behaviors of articular cartilage.     

Morphological analysis of the femoral trochlea in patients with recurrent dislocation of the patella using three-dimensional computer models

We investigated the three-dimensional morphological differences of the articular surface of the femoral trochlea in patients with recurrent dislocation of the patella and a normal control group using three-dimensional computer models. There were 12 patients (12 knees) and ten control subjects (ten knees). Three-dimensional computer models of the femur, including the articular cartilage, were created. Evaluation was performed on the shape of the articular surface, focused on its convexity, and the proximal and mediolateral distribution of the articular cartilage of the femoral trochlea. The extent of any convexity, and the proximal distribution of the articular cartilage, expressed as the height, were shown by the angles about the transepicondylar axis. The mediolateral distribution of the articular cartilage was assessed by the location of the medial and lateral borders of the articular cartilage. The mean extent of convexity was 24.9 degrees sd 6.7 degrees for patients and 11.9 degrees sd 3.6 degrees for the control group (p < 0.001). The mean height of the articular cartilage was 91.3 degrees sd 8.3 degrees for the patients and 83.3 degrees sd 7.7 degrees for the control group (p = 0.03), suggesting a wider convex trochlea in the patients with recurrent dislocation of the patella caused by the proximally-extended convex area. The lateral border of the articular cartilage of the trochlea in the patients was more laterally located than in the control group. Our findings therefore quantitatively demonstrated differences in the shape and distribution of the articular cartilage on the femoral trochlea between patients with dislocation of the patella and normal subjects.