S Santavirta

Orton Orthopaedic Hospital, Helsinki, Southern Finland Province, Finland

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Publications (342)890.26 Total impact

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    ABSTRACT: Konttinen YT, Hukkanen M, Segerberg M, Rees R, Kemppinen P, Sorsa T, Saari H, Polak JM, Santavirta S. Relationship between Neuropeptide Immunoractive Nerves and Inflammatory Cells in Adjuvant Arthritic Rats. Scand J Rheumatol 1992; 21: 55–9. The purpose of this study was to assess the relationship of neuropeptide nerves and inflammatory leukocytes in PVG rats with adjuvant-induced arthritis. Substance P- and calcitonin gene-related peptide (CGRP)-immuno reactive nerves and inflammatory leukocytes were studied, using peroxidase (ABC) andor alkaline phosphatase (APAAP) staining. Inflamed synovial tissue proper was infiltrated with neutrophils, ED1 macrophages and focal accumulations of CD2 T lymphocytes. In such tissue, the relationship between peptide-immuno reactive nerves and inflammatory cells was such that substance P and CGRP nerves were absent in heavily infiltrated villous synovial tissue, whereas healthy synovial tissue and non-inflammatory areas in adjuvant arthritic rats were innervated by substance P and CGRP nerves close to normal synovial tissue resident cells. In order to elucidate an eventual mechanism for lost immuno reactivity, healthy synovial tissue was exposed to chymotrypsin or oxygen derived free radicals (ODFR) in vitro. The former treatment caused total loss of immuno reactivity. These findings suggest that neuropeptides and neuropeptide containing nerves may be destroyed by locally produced proteolytic enzymes and various reactive oxygen species in the vicinity of inflammatory cells.
    Full-text · Article · Jul 2009 · Scandinavian Journal of Rheumatology
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    ABSTRACT: Twenty-six patients with rheumatoid arthritis (RA) participated either in a 21 day, community sponsored, in-patient multidisciplinary rehabilitation program (N=20) or; received traditional, out-patient physiotherapy designed by the patient's rheumatologist (N = 6). Clinical assessments were made (prior to, immediately after, and 6 months after rehabilitation) to evaluate the response to these two quite different rehabilitative measures that included: functional classification, joint score index, subjective VAS of pain, HAQ, Pain disability index, Comprehensible psychopathological rating scale, hemoglobin, and CRP measurements. Economic assessments included salary, direct and community sponsored costs, for rehabilitation and costs for sick days and production losses. No clear-cut differences between the two rehabilitation modes were detected. Both modes showed improvement in different assessment parameters; patients with higher education and, therefore, with a less joint-disturbing work profile appeared to profit more from an extensive in-patient rehabilitation program. Patients with less education and a more manually-oriented working profile, did worse and had a higher tendency to seek medical pensioning, in spite of rehabilitative measures. As the total costs for out-patient rehabilitation only add up to 15.8% of the total costs for in-patient rehabilitation, this study setting cautiously suggests that out-patient rehabilitation might be an acceptable alternative to individualized patient groups that might not compromise clinical and vocational outcome. Larger patient groups are needed, however, to confirm these findings.
    No preview · Article · Jul 2009

  • No preview · Article · Jul 2009 · Scandinavian Journal of Rheumatology
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    Seppo Santavirta · Yrjö T. Konttinen · Jerker Sandelin · Pär Slätis
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    ABSTRACT: Sixteen patients with seropositive rheumatoid arthritis were operated on for subaxial subluxations. Four of the patients had slight, but progressive, tetraparesis, and 5 had severe or total tetraparesis; they were operated on 1–4 months after the first signs. Seven patients were treated for severe neck and shoulder pain. Nine patients had subluxation at the C3–4 level, the most common site, and 3 patients also had an atlantoaxial subluxation. Patients with cord compression were treated with posterior laminectomies and fusions that relieved the tetraparesis. Two patients died during the early postoperative period: 1 of a cardiac infarction and the other of pneumonia. During 4 (1.5–9) years' follow-up, 3 patients had new subluxations at other levels.
    Preview · Article · Jul 2009 · Acta Orthopaedica
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    ABSTRACT: Proper mechanical loading is essential for bone remodeling and maintenance of human skeletal system. Matrix metalloproteinases (MMPs) are secreted by mesenchymal stromal lining cells and osteoblasts to prepare the initiation sites for osteoclastic bone resorption at the beginning of the remodeling cycle. However, only a few studies have addressed the effect of mechanical stress on MMPs and their endogenous tissue inhibitors of matrix metalloproteinases (TIMPs) in osteoblasts. In this study, the response of human osteoblasts to uniaxial cyclic stretching was investigated to clarify this more in detail. Stretching affected the orientation of the osteoblasts, and quantitative reverse transcription-polymerase chain reaction revealed coordinated upregulation of MMP-1 and its activator MMP-3 mRNA by cyclic 5% stretching at 3 h (p < 0.01). Upregulation of cyclooxygenase-2 mRNA was also found in response to cyclic 1 and 5% stretchings at 1, 3, and 6 h (p < 0.01). No changes were found in MMP-2, TIMP-1, and -2. The mRNA expression of MMP-9 was low and MMP-13 was not detected. This study suggests that MMP-1 and -3, enhanced by uniaxial cyclic mechanical stimulation of osteoblasts, are candidate key enzymes in the processing of collagen on bone surface, which might be necessary to allow osteoclastic recruitment leading to bone resorption. The strain might also play a role in cleaning of demineralized bone surface during the reversal phase, before bone formation starts.
    No preview · Article · Feb 2007 · Journal of Biomedical Materials Research Part B Applied Biomaterials
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    Jyrki Halinen · Jan Lindahl · Eero Hirvensalo · Seppo Santavirta
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    ABSTRACT: The apparent consensus is that solitary medial collateral ligament rupture can be treated nonoperatively, but treatment of severe combined ruptures of the medial collateral ligament and anterior cruciate ligament remains controversial. Nonoperative and early operative treatments of grade III medial collateral ligament rupture lead to similar results when the anterior cruciate ligament is reconstructed in the early phase. Randomized controlled clinical trial; Level of evidence, 1. Forty-seven consecutive patients with combined anterior cruciate ligament and grade III medial collateral ligament injuries were randomized into 2 groups. The medial collateral ligament injury was treated operatively in group 1 (n = 23) and non-operatively in group 2 (n = 24). In both groups, the anterior cruciate ligament injury was treated with early reconstruction, using bone-patellar tendon-bone graft and interference screw. Two years postoperatively, knee stability was measured with a KT-1000 arthrometer and Telos valgus radiography and knee extension strength with a Biodex dynamometer and a 1-legged hop test. An International Knee Documentation Committee evaluation form and Lysholm score were completed. All 47 patients were available for clinical evaluation for a mean of 27 months (range, 20-37 months) after surgery. There were no statistically significant differences between the 2 groups with respect to subjective function of the knee, postoperative stability, range of motion, muscle power, return to activities, Lysholm score, and overall International Knee Documentation Committee evaluation. The subjective outcome and Lysholm score were good and anteroposterior knee stability excellent in both groups. Nonoperative and operative treatments of medial collateral ligament injuries lead to equally good results. Medial collateral ligament ruptures need not be treated operatively when the anterior cruciate ligament is reconstructed in the early phase.
    Full-text · Article · Aug 2006 · The American Journal of Sports Medicine
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    ABSTRACT: Healthy bone is a rigid yet living tissue that undergoes continuous remodeling. Osteoclasts resorb bone in the remodeling cycle. They secrete H(+)-ions and proteinases to dissolve bone mineral and degrade organic bone matrix, respectively. One of the main collagenolytic proteinase in osteoclasts is cathepsin K, a member of papain family cysteine proteinases. Recently, it has been shown that osteoblasts may contribute to organic matrix remodeling. We therefore investigated their ability to produce cathepsin K for this action. Trabecular bone samples were collected from patients operated due to a fracture of the femoral neck. Part of the bone was decalcified and the rest was used for cell isolation. Sections from the decalcified bone were immunostained with antibodies against cathepsin K. Isolated cells were characterized for their ability to form mineralized matrix and subsequently analyzed for their cathepsin K production by Western blotting and quantitative RT-PCR. Osteoblasts, bone lining cells and some osteocytes in situ showed cathepsin K immunoreactivity and osteoblast-like cells in vitro produced cathepsin K mRNA and released both 42 kDa pro- and 27 kDa processed cathepsin K to culture media. Osteoblastic cathepsin K may thus contribute to collagenous matrix maintenance and recycling of improperly processed collagen I. Whether osteoblastic cathepsin K synthesis has consequences in diseases characterized by abnormal bone matrix turnover remains to be investigated.
    Full-text · Article · Jul 2006 · Bone
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    ABSTRACT: It was hypothesized that peri-implant tissue around loosening dental implants may contain cytokines with a potential to regulate osteoclasts. Peri-implant and/or gingival samples from loosened implants, chronic periodontitis (CP), and normal controls (n = 10 samples in each group) were analyzed using immunohistochemical staining to observe tumor necrosis factor alpha (TNF-alpha), interleukin 1-alpha (IL-1alpha), IL-6, platelet-derived growth factor A (PDGF-A), and transforming growth factor alpha (TGF-alpha). These cytokines were found in foreign-body giant cells, macrophages, fibroblasts, and epithelial cells. TNF-alpha, IL-1alpha, and IL-6 were increased (P < .05; unpaired t test) in peri-implantitis and CP, whereas PDGF-A and TGF-alpha were not. In conclusion, cytokines with a potential to activate osteoclasts were found in both peri-implantitis and CP, but the cytokine profiles differed in that IL-1alpha was the most prevalent cytokine in the former and TNF-alpha was the most common in the latter. These cytokines may contribute to peri-implant bone loss/loosening by stimulating formation and activity of osteoclasts and might be an amenable target for local therapies with cytokine modulators.
    No preview · Article · May 2006 · The International journal of periodontics & restorative dentistry
  • Arto Koistinen · Seppo S Santavirta · Heikki Kröger · Reijo Lappalainen
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    ABSTRACT: In this study, the potential of high-quality amorphous diamond (AD) coatings in reducing the torque and failures of bone screws was studied. Torque values were recorded for 32 stainless steel screws, 2.7 or 3.5 mm in diameter and 60 mm in length. Half of the screw sets were coated with the AD coating before installing in predrilled holes of human cadaveric femoral bone samples. The bone samples were selected from two groups of four persons with mean ages of 34 years (range 25-41 years) and 75 years (range 73-77 years), respectively. The bone mineral density (BMD) values of the samples were determined exactly at the screw insertion site by peripheral quantitative computed tomography (pQCT). In the mechanical tests, insertion and removal torques were measured. BMD had a significant effect on insertion torque; the maximum torque (adjusted with respect to the screw diameter) was significantly higher for the young bone than for the old bone (p < 0.05). By using a polished AD coating, insertion torque was decreased even up to 50% in comparison with the screws without coating. The results suggest that AD coating provides a stable, smooth surface and reduces the risk of screw failures.
    No preview · Article · Nov 2005 · Biomaterials
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    Yrjö T Konttinen · Seppo Seitsalo · Matti Lehto · Seppo Santavirta

    Full-text · Article · Nov 2005 · Acta Orthopaedica
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    ABSTRACT: To assess the expression and processing of a disintegrin and metalloproteinase, ADAM 12 (meltrin-alpha), in the formation of multinuclear cells. Methods. In situ hybridization, immunohistochemical staining, and Western blotting of interface membrane around loosened total hip replacement implants. Macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor-kappaB ligand (RANKL) costimulation of human monocytes followed by FACS, immunofluorescence staining, Western blotting, and bone resorption assay. ADAM 12 mRNA-containing mononuclear cells were often seen in a close spatial relationship with ADAM 12-positive multinuclear cells. Morphometric analysis of ADAM 12 disclosed that 53% +/- 2% of all interface cells were ADAM 12-positive compared to 5% +/- 1% in controls (p < 0.001). M-CSF and RANKL were richly present in interface tissue around loosening implants. Upon M-CSF and RANKL costimulation of human monocytes in vitro, the ADAM 12 staining pattern changed over time, and ADAM 12-positive cells formed large mono-, bi-, and multinuclear cells at Day 7 and many multinuclear giant cells and/or osteoclasts at Day 14. Western blot disclosed 90 kDa latent ADAM 12L but also the metalloproteinase-cleaved, fusion-active 60 kDa form transiently just before the burst of fusion. ADAM 12, well recognized for participation in cell-cell fusion in myoblast formation, is upregulated and processed upon formation of multinuclear giant cells and osteoclasts. It may play a role in formation of giant cells and osteoclasts around loosened total hip replacement implants.
    No preview · Article · Oct 2005 · The Journal of Rheumatology
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    ABSTRACT: Interface tissue between the bone and loosening total hip implant is acidic and highly osteolytic. It is characterized by the formation of cathepsin K positive foreign body giant cells. Similar structures to those found in the normal joint surround the artificial hip joint. Cells in synovial membrane of the artificial hip generate synovial fluid that is called pseudosynovial fluid. Interface tissue fibroblasts are able to produce receptor activator of NF-kappaB ligand (RANKL), which can induce osteoclastogenesis during the loosening process. Western blot analysis indicated that RANKL is present in the pseudosynovial fluid. Pseudosynovial fluid induced cultured peripheral blood mononuclear cells to form multinuclear TRAP positive giant cells. In the presence of osteoprotegerin, the soluble RANKL decoy receptor, the number of TRAP positive multinuclear cells was reduced to half (p < 0.05). The multinuclear cells induced with pseudosynovial fluid contained active cathepsin K protein and were capable of bone matrix resorption in vitro. The cells were shown to express osteoclast phenotype markers, such as mRNA for cathepsin K, TRAP, and calcitonin receptor. It is therefore apparent that pseudosynovial fluid from patients with aseptic loosening of total hip prosthesis contains a potent osteoclastogenic factor RANKL that further suggests a favorable environment for osteoclast formation in the peri-implant tissues. It is thus concluded that suppression of RANKL activity may be beneficial in terms of increasing the lifetime of total hip prostheses.
    Full-text · Article · Jul 2005 · Journal of Biomedical Materials Research Part B Applied Biomaterials
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    ABSTRACT: The highly osteolytic interface tissue between the bone and loosening total hip prosthesis is characterized by low pH, formation of foreign body giant cells, osteoclasts, and production of receptor activator of nuclear factor-kappaB (RANKL) and cathepsin K. We hypothesized that fibroblasts in the interface tissue may form a source for RANKL production. Primary interface tissue fibroblasts, fibrous joint capsule fibroblasts, and trabecular bone osteoblasts were stimulated with tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), IL-6, IL-11, or 1alpha,25-(OH)2 vitamin D3. Cellular RANKL and released cathepsin K were detected by Western blotting. RANKL in cell lysates and osteoprotegerin (OPG) in cell culture medium were measured by ELISA. RANKL, OPG, and cathepsin K mRNA were measured with quantitative reverse transcriptase polymerase chain reaction. Interface tissue fibroblasts were found to produce RANKL. 1alpha,25-(OH)2 vitamin D3 stimulation increased RANKL mRNA expression. TNF-alpha was found to be the most potent OPG inducer in interface tissue fibroblasts. Cathepsin K mRNA production in fibroblasts was upregulated roughly 3-fold (p < 0.01) after 1alpha,25-(OH)2D3 stimulation, and both pro- and active cathepsin K protein was released to fibroblast culture media. Interface tissue fibroblasts are able to produce RANKL, OPG, and cathepsin K and may contribute indirectly and directly to pathologic periprosthetic collagenolysis and bone destruction.
    Full-text · Article · Apr 2005 · The Journal of Rheumatology
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    ABSTRACT: The most common cause for heel pain is plantar fasciitis. The diagnosis can usually be made by clinical examination, but sometimes ENMG (electroneuromyography), ultrasound, and magnetic resonance imaging examinations are helpful. Other reasons for heel pain, e.g., nerve entrapments, atherosclerosis/ischemia, and fat pad degeneration, should be excluded. Plantar fasciitis can also present a symptom of chronic seronegative spondyloarthropathies or reactive arthritis. In the case of common plantar fasciitis, three different modes of treatment can be administered, namely, (1) anti-inflammatory and analgesic treatment, (2) rest and diminution of the strain at the insertion, and (3) maintenance of the tension and flexibility of the soft tissues. A simple four-step treatment plan algorithm, based on symptoms, their duration, and response to treatment, is presented. Operative treatment is seldom needed if the algorithm is correctly followed. Operative treatment is recommended only when the pain remains resistant to conservative treatment after more than 1 year. For operative treatment, partial release of the fascia close to insertion to avoid flat foot and secondary strain on the calcaneocuboid and midtarsal (Lisfranc) joints is our preferred option.
    No preview · Article · Feb 2005 · Modern Rheumatology
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    ABSTRACT: Contact pressure of UHMWPE acetabular cup has been shown to correlate with wear in total hip replacement (THR). The aim of the present study was to test the hypotheses that the cup geometry, abduction angle, thickness and clearance can modify the stresses in cemented polyethylene cups. Acetabular cups with different geometries (Link: IP and Lubinus eccentric) were tested cyclically in a simulator at 45 degrees and 60 degrees abduction angles. Finite element (FE) meshes were generated and two additional designs were reconstructed to test the effects of the cup clearance and thickness. Contact pressures at cup-head and cup-cement interfaces were calculated as a function of loading force at 45 degrees, 60 degrees and 80 degrees abduction angles. At the cup-head interface, IP experienced lower contact pressures than the Lubinus eccentric at low loading forces. However, at higher loading forces, much higher contact pressures were produced on the surface of IP cup. An increase in the abduction angle increased contact pressure in the IP model, but this did not occur to any major extent with the Lubinus eccentric model. At the cup-cement interface, IP experienced lower contact pressures. Increased clearance between cup and head increased contact pressure both at cup-head and cup-cement interfaces, whereas a decreased thickness of polyethylene layer increased contact pressure only at the cup-cement interface. FE results were consistent with experimental tests and acetabular cup deformations. FE analyses showed that geometrical design, thickness and abduction angle of the acetabular cup, as well as the clearance between the cup and head do change significantly the mechanical stresses experienced by a cemented UHMWPE acetabular cup. These factors should be taken into account in future development of THR prostheses. FE technique is a useful tool with which to address these issues.
    Full-text · Article · Feb 2005 · BioMedical Engineering OnLine
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    ABSTRACT: The metal stem of the totally replaced hip carries load and resists fatigue, but it is electrochemically corroded. Metallic atoms act as haptens, induce type 1 T-helper cells/Th1-type immune responses and enhance periprosthetic osteolysis. Stiff metal implants, which do not have the same elasticity as the surrounding bone, cause stress shielding. Cyclic loading and lack of ligamentous support lead to mechanical and ischemia reperfusion injury and particle formation from bone, polymethylmethacrylate, and porous implant surfaces, which accelerate third-body polyethylene wear. Surgical injury and micromotion induce the formation of a fibrous capsule interface. Type-B lining cells produce lubricin and surface-active phospholipids to promote solid-to-solid lubrication but may loosen the implant from bone. The pumping action of the cyclically loaded joint and synovial fluid pressure waves dissect the implant-host interface and transports polyethylene particles and pro-inflammatory mediators to the interface. Hyaluronan induces formation of a synovial lining like layer. Because of its localization close to bone, foreign body inflammation at the interface stimulates osteoclastogenesis and peri-implant bone loss. Metal-on-metal and ceramic-on-ceramic pairs might minimize third body wear, but can lead to high-impact load of the acetabulum. Diamond coating of a metal-on-polyethylene couple might solve both of these problems. The basic biomaterial solutions allow good mechanical performance and relatively long life in-service, but surface modifications (porous coating, hydroxyapatite, diamond, bioglass, and others) may facilitate performance of the implant and improve the biomaterial and body interfaces.
    No preview · Article · Feb 2005 · Clinical Orthopaedics and Related Research
  • Seppo Santavirta · Stuart B Goodman

    No preview · Article · Feb 2005 · Clinical Orthopaedics and Related Research
  • Reijo Lappalainen · Seppo S Santavirta
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    ABSTRACT: In total hip replacements, the bulk properties of materials, such as proper elasticity and hardness, are important. However, the material interacts with the body mainly at the surfaces. Wear and corrosion are initiated at the surfaces also. Therefore, the control of surface properties using different kinds of treatments or coatings may improve total hip replacements considerably. The most studied surface treatments include ion implantation and methods to control surface topography, such as grit or sand blasting or plasma treatments. Among the large variety of coatings, hydroxyapatite, titanium oxide and nitride, zirconium oxide, pyrolytic carbon, and diamondlike carbon coatings have shown the most promising results. These coatings mainly are used to enhance bone growth; to minimize friction, wear, and corrosion; and to improve biocompatibility of total joint prostheses. The potential of novel coatings to solve some present problems in joint prostheses is discussed based on the structure and properties of different kind of coatings. It can be concluded that currently, coating methods exist to improve the tribologic performance and longevity of the total hip replacements. However, coatings must fulfill two essential requirements: no delamination in biochemical and biomechanical environments and sufficient protection of substrate from corrosion.
    No preview · Article · Feb 2005 · Clinical Orthopaedics and Related Research
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    YT Konttinen · J Ma · P Ruuttilal · M Hukkanen · S Santavirta
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    ABSTRACT: Osteoarthritis (OA) is associated with destruction of type II collagen-rich hyaline articular cartilage. We hypothesized that classical interstitial collagenases cleave collagen type II, leading to the increased expression of the 3/4 native type II collagen fragment (COL2-3/4C) and the corresponding denatured type II collagen fragment (COL2-3/4M), which could correlate with different cartilage destruction grades. In addition, we assessed whether these fragments could be measured in joint fluid and serve as diagnostic markers. Cartilage specimens were obtained from the femoral heads of hip joints from total hip replacement operations. Articular gliding surfaces of the cartilage were categorized into normal (G0), fibrillated (G1), superficiallyfissured (G2) and deeplyfissured (fissures that reach to the subchondral bone) (G3). A histological scoring of the cartilage was also used. COL2-3/4C and COL2-3/4M were detected by immunohistochemical staining. Dot blotting was used to detect these fragments in joint fluid. COL2-3/4C and COL2-3/4M were found in the perichondrocyte matrix around lacunae. Such COL2-3/4C (p < 0.05) and COL2-3/4M (p < 0.05) immunoreactivity was significantly increased in G3 and G2 compared to GO and G1. A positive correlation (n = 35, Spearman rank correlation) was observed between the histological score and the percentage of COL2-3/4C positive lacunae (r = 0.43, p = 0.01) and COL2- 3/4M positive lacunae (r = 0.53, p = 0.001). All 7/7 joint fluid samples contained COL2-3/4C in dot blots whereas only 4/7 contained COL2-3/4M. Collagenase-cleaved collagen--both native and denatured--increases as the severity of OA increases, assessed using a macroscopic clinical and microscopic histological grading system. Collagen degradation was always most apparent around chondrocytes. Furthermore, the native COL2-3/4C fragment has potential as a joint fluid marker for OA.
    Full-text · Article · Jan 2005 · Clinical and experimental rheumatology
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    ABSTRACT: Bioabsorbable fixation devices are increasingly used in trauma, orthopedic and craniomaxillofacial surgery. The devices are essentially made of polylactic acid and/or polyglycolic acid polymers. Ultra-high-strength implants are manufactured from such polymers using self-reinforcing techniques. Implants are available for stabilization of fractures, osteotomies, bone grafts and fusions, as well as for reattachment of ligaments, tendons, meniscal tears and other soft tissue structures. As these implants are completely absorbed, the need for a removal operation is overcome and long-term interference with tendons, nerves and the growing skeleton is avoided. The risk of implant-associated stress shielding, peri-implant osteoporosis and infections is reduced. Implants do not interfere with clinical imaging. Current clinical use of bioabsorbable devices is reviewed.
    No preview · Article · Dec 2004 · Expert Review of Medical Devices

Publication Stats

8k Citations
890.26 Total Impact Points


  • 1989-2009
    • Orton Orthopaedic Hospital
      Helsinki, Southern Finland Province, Finland
  • 1988-2009
    • ORTON Foundation, Helsinki, Finland
      Helsinki, Southern Finland Province, Finland
  • 1977-2009
    • Helsinki University Central Hospital
      • • Department of Medicine
      • • Department of Orthopaedics and Traumatology
      • • Surgical Hospital
      Helsinki, Province of Southern Finland, Finland
  • 1987-2005
    • University of Helsinki
      • • Department of Anatomy
      • • Department of Oral Pathology
      • • IV Department of Surgery
      • • Department of Pathology
      Helsinki, Uusimaa, Finland
  • 2004
    • Hospital District for Helsinki and Uusimaa
      Helsinki, Southern Finland Province, Finland
  • 1999
    • Aarhus University
      • Department of Biomedicine
      Aarhus, Central Jutland, Denmark
  • 1998
    • University of Florence
      Florens, Tuscany, Italy
  • 1992
    • NYU Langone Medical Center
      • New York University School of Medicine and Medical Center
      New York, New York, United States
  • 1978
    • University of Turku
      • Department of Surgery
      Turku, Southwest Finland, Finland