| 1. |
- Vasara, Anna I, et al.
(författare)
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Subchondral bone reaction associated with chondral defect and attempted cartilage repair in goats.
- 2004
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 74:1, s. 107-14
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Tidskriftsartikel (refereegranskat)abstract
- Repair of cartilage damage with autologous chondrocyte transplantation (ACT) has become popular in clinical use during the past few years. Although clinical results have mostly been successful, several unanswered questions remain regarding the biological mechanism of the repair process. The aim of this study was to develop a goat model for ACT. The repair was not successful due to the graft delamination, but we characterize the subchondral changes seen after the procedure. A chondral lesion was created in 14 goat knees, operated on 1 month later with ACT, and covered with periosteum or a bioabsorbable poly-L/D-lactide scaffold. After 3 months, only two of the five lesions repaired with ACT showed partly hyaline-like repair tissue, and all lesions (n = 4) with the scaffold failed. Even though the lesions did not extend through the calcified cartilage, the bone volume and collagen organization of bone structure were decreased when assessed by quantitative polarized light microscopy. There was a significant loss of bone matrix and distortion of the trabecular structure of subchondral bone, which extended several millimeters into the bone. The subchondral bone demonstrated strong hyaluronan staining in the bone marrow and cartilaginous areas with signs of endochondral ossification, suggesting structural remodeling of the bone. The goat model used here proved not to be an optimal model for ACT. The changes in subchondral bone may alter the biomechanical properties of the subchondral plate and thus the long-term survival of the repair tissue after ACT.
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| 2. |
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| 3. |
- Bjorvang, Richelle D., et al.
(författare)
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Persistent organic pollutants, pre-pregnancy use of combined oral contraceptives, age, and time-to-pregnancy in the SELMA cohort
- 2020
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Ingår i: Environmental Health. - : BMC. - 1476-069X. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background We are exposed to several chemicals such as persistent organic pollutants (POPs) in our everyday lives. Prior evidence has suggested that POPs may have adverse effects on reproductive function by disrupting hormone synthesis and metabolism. While there is age-related decline of fertility, the use of hormonal combined oral contraceptives (COCs) and its association to return of fertility remains controversial. The goal of this study is to investigate the association between exposure to POPs, both individually and as a mixture, and fecundability measured as time-to-pregnancy (TTP) according to pre-pregnancy use of COCs and age. Methods Using the SELMA (Swedish Environmental Longitudinal Mother and Child, Allergy and Asthma) study, we have identified 818 pregnant women aged 18-43 years (mean 29 years) with data on how long they tried to get pregnant and what was their most recently used contraceptive method. These data were collected at enrollment to the study (median week 10 of pregnancy). Concentrations of 22 POPs and cotinine were analyzed in the blood samples collected at the same time as the questions on TTP and pre-pregnancy use of contraceptive. Analyses were done on the association between POPs exposure and TTP measured as continuous (months) and binary (infertile for those with TTP > 12 months). To study the chemicals individually, Cox regression and logistic regression were used to estimate fecundability ratios (FRs) and odds ratios (ORs), respectively. Weighted quantile sum (WQS) regression was used to investigate the chemicals as a mixture where chemicals of concern were identified above the 7.6% threshold of equal weights. To perform the subgroup analysis, we stratified the sample according to use of COCs as the most recent pre-pregnancy contraception method and age (< 29 years, and >= 29 years). The models were adjusted for parity, regularity of menses, maternal body mass index (BMI) and smoking status, and stratified as described above. Results Prior to stratification, none of the POPs were associated with fecundability while increased exposure to HCB, PCB 74 and 118 had higher odds of infertility. Upon stratification, POP exposure was significantly associated with longer TTP in women aged >= 29 years who did not use COC. Specifically, PCBs 156, 180, 183, and 187 were associated with reduced fecundability while PCBs 99, 153, 156, 180, 183, and 187 had higher odds of infertility. As a mixture, we identified the chemicals of concern for a longer TTP include PCBs 118, 156, 183, and 187. Moreover, chemicals of concern identified with increased odds of infertility were PCB 74, 156, 183, 187, and transnonachlor. Conclusion Serum concentrations of selected POPs, both as individual chemicals and as a mixture, were significantly associated with lower fecundability and increased odds of infertility in women aged 29 years and above not using COC as their most recent pre-pregnancy contraceptive. Our findings suggest that pre-pregnancy use of oral contraceptive and age may modify the link between POPs and fecundability. The differences of specific chemicals in the individual analysis and as a mixture support the need to study combination effects of chemicals when evaluating reproductive outcomes.
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| 4. |
- Haapala, J, et al.
(författare)
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Decline after immobilisation and recovery after remobilisation of synovial fluid IL1, TIMP, and chondroitin sulphate levels in young beagle dogs
- 2001
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 60:1, s. 55-60
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To monitor the concentration of markers of cartilage and synovium metabolism in the knee (stifle) joint synovial fluid of young beagles subjected to immobilisation and subsequent remobilisation.METHODS: The right hind limb of 17 dogs was immobilised in flexion for 11 weeks. Simultaneously, the contralateral left knee was exposed to increased weight bearing. The remobilisation period lasted 50 weeks. Litter mates served as controls. The concentration in joint lavage fluid of interleukin 1 (IL1) was measured by immunoassay, the activity of phospholipase A2 (PLA2) was determined by an extraction method, chondroitin sulphate (CS) concentration by precipitation with Alcian blue, hyaluronan (HA) by an ELISA-like assay using biotinylated HA-binding complexes, matrix metalloproteinase 3 (MMP-3), and tissue inhibitor of metalloproteinases 1 (TIMP-1) by sandwich ELISA, and synovitis was scored by light microscopy.RESULTS: Synovitis or effusion was absent in all experimental and control groups. Immobilisation decreased the joint lavage fluid levels of IL1 (p<0.05), TIMP (p< 0.05), and the concentration of CS down to 38 (p<0.05) in comparison with untreated litter mates with normal weight bearing. Immobilisation did not affect the activity of PLA2, or the concentration of MMP-3 or HA in synovial fluid. Joint remobilisation restored the decreased concentrations of markers to control levels. Increased weight bearing did not change the concentrations of markers in comparison with the control joints with normal weight bearing.CONCLUSIONS: 11 weeks joint immobilisation decreased the concentration of markers of cartilage and synovium metabolism in the synovial fluid, and remobilisation restored the concentrations to control levels. The changes in joint metabolism induced by immobilisation, as reflected by the markers, are thus different from those found in osteoarthritis, where increased levels of these markers are associated with enhanced degradation and synthesis. These findings suggest that the change induced in joint metabolism by immobilisation is reversible in its early stages.
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| 5. |
- Pulliainen, Outi, et al.
(författare)
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Poly-L-D-lactic acid scaffold in the repair of porcine knee cartilage lesions.
- 2007
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Ingår i: Tissue engineering. - : Mary Ann Liebert Inc. - 1076-3279 .- 1557-8690. ; 13:6, s. 1347-55
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Tidskriftsartikel (refereegranskat)abstract
- Articular cartilage injuries cause a major clinical problem because of the negligible repair capacity of cartilage. Autologous chondrocyte transplantation is a surgical method developed to repair cartilage lesions. In the operation, cartilage defect is covered with a periosteal patch and the suspension of cultured autologous chondrocytes is injected into the lesion site. The method can form good repair tissue, but new techniques are needed to make the operation easier and to increase the postoperative biomechanical properties of the repair tissue. In this study, we investigated poly-L,D-lactic acid (PLDLA) scaffolds alone or seeded with autologous chondrocytes in the repair of circular 6-mm cartilage lesions in immature porcine knee joints. Spontaneous repair was used as a reference. Histologic evaluation of the repair tissue showed that spontaneous repair exhibited higher scores than either PLDLA scaffold group (with or without seeded chondrocytes). The scaffold material was most often seen embedded in the subchondral bone underneath the defect area, probably because of the hardness of the PLDLA material. However, some of the cell-seeded and nonseeded scaffolds contained cartilaginous tissue, suggesting that invasion of mesenchymal cells inside nonseeded scaffolds had occurred. Hyaluronan deposited in the scaffold had possibly acted as a chemoattractant for the cell recruitment. In conclusion, the PLDLA scaffold material used in this study was obviously mechanically too hard to be used for cartilage repair in immature animals.
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| 6. |
- Vasara, Anna I., et al.
(författare)
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Arthroscopic cartilage indentation and cartilage lesions of anterior cruciate ligament-deficient knees
- 2005
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Ingår i: AMERICAN JOURNAL OF SPORTS MEDICINE. - : SAGE Publications. - 0363-5465 .- 1552-3365. ; 33:3, s. 408-414
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Tidskriftsartikel (refereegranskat)abstract
- The anterior cruciate ligament-deficient knee is prone to osteoarthritis and meniscus lesions. Very little, however, is known about the biomechanical properties of articular cartilage in anterior cruciate ligament-deficient knees. Purpose To evaluate biomechanical and macroscopical cartilage changes in the knee joint with respect to the time after anterior cruciate ligament rupture. Hypothesis Chronic anterior cruciate ligament deficiency induces cartilage softening. Study Design Cross-sectional study; Level of evidence, 3. Methods Cartilage stiffness of 50 patients undergoing anterior cruciate ligament reconstructive surgery because of symptomatic knee instability after chronic anterior cruciate ligament rupture was measured with an arthroscopic indenter device, and the number and size of cartilage lesions were evaluated. Results The cartilage stiffness did not correlate with time from trauma to surgery (r = 0.002, P =. 99), but the number of cartilage lesions in the knee increased when the time from the initial trauma to reconstructive surgery increased (r = 0.356, P =. 011). Indentation values measured on healthy-looking cartilage on damaged joint surfaces were lower than the values measured on healthy joint surfaces (P <. 01 on lateral femoral condyle and on tibial plateaus). Conclusions The number of cartilage lesions increases with increased time after initial trauma. The arthroscopic indenter device is able to detect cartilage softening as the early mechanical sign of degradation not yet visible to the eye.
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| 7. |
- Vasara, Anna I, et al.
(författare)
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Immature porcine knee cartilage lesions show good healing with or without autologous chondrocyte transplantation.
- 2006
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Ingår i: Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. - : Elsevier BV. - 1063-4584 .- 1522-9653. ; 14:10, s. 1066-74
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The purpose of this study was to find out how deep chondral lesions heal in growing animals spontaneously and after autologous chondrocyte transplantation. METHODS: A 6mm deep chondral lesion was created in the knee joints of 57 immature pigs and repaired with autologous chondrocyte transplantation covered with periosteum or muscle fascia, with periosteum only, or left untreated. After 3 and 12 months, the repair tissue was evaluated with International Cartilage Repair Society (ICRS) macroscopic grading, modified O'Driscoll histological scoring, and staining for collagen type II and hyaluronan, and with toluidine blue and safranin-O staining for glycosaminoglycans. The repair tissue structure was also examined with quantitative polarized light microscopy and indentation analysis of the cartilage stiffness. RESULTS: The ICRS grading indicated nearly normal repair tissue in 65% (10/17) after the autologous chondrocyte transplantation and 86% (7/8) after no repair at 3 months. At 1 year, the repair tissue was nearly normal in all cases in the spontaneous repair group and in 38% (3/8) in the chondrocyte transplantation group. In most cases, the cartilage repair tissue stained intensely for glycosaminoglycans and collagen type II indicating repair tissue with true constituents of articular cartilage. There was a statistical difference in the total histological scores at 3 months (P=0.028) with the best repair in the spontaneous repair group. A marked subchondral bone reaction, staining with toluidine blue and collagen type II, was seen in 65% of all animals. CONCLUSIONS: The spontaneous repair ability of full thickness cartilage defects of immature pigs is significant and periosteum or autologous chondrocytes do not bring any additional benefits to the repair.
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| 8. |
- Vasara, Anna I, et al.
(författare)
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Indentation stiffness of repair tissue after autologous chondrocyte transplantation.
- 2005
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Ingår i: Clinical orthopaedics and related research. - 0009-921X. ; :433, s. 233-42
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Tidskriftsartikel (refereegranskat)abstract
- Our main hypothesis was that indentation stiffness of the repair tissue approaches the values of adjacent cartilage 1 year after autologous chondrocyte transplantation. We also wanted to investigate the differences between osteochondritic lesions and full-thickness lesions. Thirty patients with cartilage lesions were operated on with autologous chondrocyte transplantation. The repair was evaluated arthroscopically, indentation stiffness was measured, and clinical evaluations were done. The stiffness of the repair tissue improved to 62% (mean 2.04 +/- 0.83 N, mean +/- SD) of adjacent cartilage (3.58 +/- 1.04 N). Fifty-three percent of the patients graded their knee as excellent or good and 47% of the patients graded their knee as fair at the followup. In six patients the normalized stiffness was at least 80%, suggesting hyaline-like repair. The indentation stiffness of the osteochondritis dissecans lesion repairs (1.45 +/- 0.46 N; n = 7) was less than that of the nonosteochondritis dissecans lesion repair sites (2.37 +/- 0.72 N; n = 19). Gadolinium-enhanced magnetic resonance imaging of the cartilage (dGEMRIC) during followup of four patients suggested proteoglycan replenishment, although all grafts showed low indentation values. Low stiffness values may indicate incomplete maturation or predominantly fibrous repair. The indentation analysis showed that the repair tissue stiffness could, in some cases, reach the same level as the adjacent cartilage, but there was a large variation among the grafts.
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| 9. |
- Vasara, Anna I, et al.
(författare)
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Persisting high levels of synovial fluid markers after cartilage repair: a pilot study.
- 2009
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Ingår i: Clinical orthopaedics and related research. - : Ovid Technologies (Wolters Kluwer Health). - 1528-1132 .- 0009-921X. ; 467:1, s. 267-72
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Tidskriftsartikel (refereegranskat)abstract
- Local attempts to repair a cartilage lesion could cause increased levels of anabolic and catabolic factors in the synovial fluid. After repair with regenerated cartilage, the homeostasis of the cartilage ideally would return to normal. In this pilot study, we first hypothesized levels of synovial fluid markers would be higher in patients with cartilage lesions than in patients with no cartilage lesions, and then we hypothesized the levels of synovial fluid markers would decrease after cartilage repair. We collected synovial fluid samples from 10 patients before autologous chondrocyte transplantation of the knee. One year later, a second set of samples was collected and arthroscopic evaluation of the repair site was performed. Fifteen patients undergoing knee arthroscopy for various symptoms but with no apparent cartilage lesions served as control subjects. We measured synovial fluid matrix metalloproteinase-3 (MMP-3) and insulinlike growth factor-I (IGF-I) concentrations with specific activity and enzyme-linked immunosorbent assays, respectively. The levels of MMP-3 and IGF-I were higher in patients having cartilage lesions than in control subjects with no cartilage lesions. One year after cartilage repair, the lesions were filled with repair tissue, but the levels of MMP-3 and IGF-I remained elevated, indicating either graft remodeling or early degeneration. Level of Evidence: Level III, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
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