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Seppo Santavirta

Publications and source records attributed to Seppo Santavirta.

35 records · Page 2Linked to original sources

Direct evidence of collagenolysis in chronic periodontitis.

BACKGROUND: There is no previous evidence that collagenases in chronic periodontitis excessively cleave collagen fibrils. OBJECTIVES: In this study the eventual presence of neoepitopes produced in such a cleavage were looked for. METHODS: A polyclonal antibody, which recognizes collagenase-cleaved collagen type I 3/4 carboxy-terminal neoepitope (COL1-3/4C), was used in avidin-biotin-peroxidase complex staining. RESULTS: In addition, moderate staining was seen in connective tissue bordering to the sulcular and junctional epithelium, surrounding some of the fibroblasts and in some areas infiltrated by inflammatory mononuclear cells. COL1-3/4C staining in chronic periodontitis was more extensive (6.3 +/- 1.2%, n = 10) and intense than that observed in controls (1.6 +/- 0.7%, n = 10, Unpaired Student's t-test, p < 0.01). CONCLUSIONS: It is concluded that collagenases produced by host cells contribute to periodontal tissue destruction and attachment loss.

Adolescent↗

Alternative materials to improve total hip replacement tribology.

An improvement in tribology of bearing surfaces is an effective means of increasing the longevity of total hip replacement (THR). Currently, 3 approaches are available to achieve this aim: first, use of highly cross-linked UHMWPE; second, aluminum oxide ceramic bearings, and third, metal-on-metal bearings. Cross-linking reduces the wear resistance of UHMWPE markedly without impairment of other significant properties of the material. Simulator studies and some clinical long-term (10-22 years) follow-up surveys suggest an almost immeasurable wear of the highly cross-linked UHMWPE-based acetabular components during an expected clinical life span. Bioinert alumina ceramic (aluminum oxide) was introduced 3 decades ago for THR-bearing surfaces to improve performance and longevity. Alumina ceramic is entirely biostable and bioinert and has good mechanical properties. For correctly positioned alumina-on-alumina bearings, the annual linear wear rate has been reported to be 3.9 microm. Alumina heads have been successfully used in combination with polyethylene sockets, but as regards wear, the best results have been obtained with alumina-on-alumina bearings. In ceramic THR bearings, precise manufacture and contact surface geometry, including optimal clearance, are most important. For the currently available products, the component fracture risk is almost nonexistent (less than 1 per 1000). Metal-on-metal bearings were used in the early stage of THR surgery, although not all old designs were successful. More recent analyses of the early series have shown the advantages of metal-on-metal to be better and have led to a renaissance of this articulation. Initially, stainless steel was used because it was easy to manufacture and polish. Current metal-on-metal bearings are based on cobalt-chromium-molybdenum alloys with varying carbon contents. Such bearings are self-polishing. Linear wear rates remain at the level of a few microm a year. An improvement in technology has increased the life span of the above three THR-bearing systems. Although the technical solutions differ considerably, they all seem to improve clearly the tribology and longevity of the THR. Each of these bearing concepts will probably permit the use of larger head sizes, to reduce the risk of impingement and luxations.

Aluminum Oxide↗

Compatibility of the totally replaced hip. Reduction of wear by amorphous diamond coating.

Particulate wear debris in totally replaced hips causes adverse local host reactions. The extreme form of such a reaction, aggressive granulomatosis, was found to be a distinct condition and different from simple aseptic loosening. Reactive and adaptive tissues around the totally replaced hip were made of proliferation of local fibroblast like cells and activated macrophages. Methylmethacrylate and high-molecular-weight polyethylene were shown to be essentially immunologically inert implant materials, but in small particulate form functioned as cellular irritants initiating local biological reactions leading to loosening of the implants. Chromium-cobalt-molybdenum is the most popular metallic implant material; it is hard and tough, and the bearings of this metal are partially self-polishing. In total hip implants, prerequisites for longevity of the replaced hip are good biocompatibility of the materials and sufficient tribological properties of the bearings. The third key issue is that the bearing must minimize frictional shear at the prosthetic bone-implant interface to be compatible with long-term survival. Some of the approaches to meet these demands are alumina-on-alumina and metal-on-metal designs, as well as the use of highly crosslinked polyethylene for the acetabular component. In order to avoid the wear-based deleterious properties of the conventional total hip prosthesis materials or coatings, the present work included biological and tribological testing of amorphous diamond. Previous experiments had demonstrated that a high adhesion of tetrahedral amorphous carbon coatings to a substrate can be achieved by using mixing layers or interlayers. Amorphous diamond was found to be biologically inert, and simulator testing indicated excellent wear properties for conventional total hip prostheses, in which either the ball or both bearing surfaces were coated with hydrogen-free tetrahedral amorphous diamond films. Simulator testing with such total hip prostheses showed no measurable wear or detectable delamination after 15,000,000 test cycles corresponding to 15 years of clinical use. The present work clearly shows that wear is one of the basic problems with totally replaced hips. Diamond coating of the bearing surfaces appears to be an attractive solution to improve longevity of the totally replaced hip.

Arthroplasty, Replacement, Hip↗

Bioabsorbable miniplating versus metallic fixation for metacarpal fractures.

Bioabsorbable implants offer an attractive alternative to metallic implants to stabilize small bone fractures in the hand. Self-reinforced bioabsorbable miniplating for metacarpal fractures was studied in bones from cadavers and compared with standard metallic fixation methods. One hundred twelve fresh-frozen metacarpals from humans had three-point bending and torsional loading after transverse osteotomy followed by fixation using seven methods: (1) dorsal and (2) dorsolateral 2-mm self-reinforced polylactide-polyglycolide 80/20 plating, (3) dorsal and (4) dorsolateral 2-mm self-reinforced poly-L/DL-lactide 70/30 plating, (5) dorsal 1.7-mm titanium plating, (6) dorsal 2.3-mm titanium plating, and (7) crossed 1.25-mm Kirschner wires. In apex dorsal and palmar bending, dorsal self-reinforced polylactide-polyglycolide and poly-L/DL-lactide plates provided stability comparable with dorsal titanium 1.7-mm plating. When the bioabsorbable plates were applied dorsolaterally, apex palmar rigidity was increased and apex dorsal rigidity was decreased. Bioabsorbable platings resulted in higher torsional rigidity than 1.7-mm titanium plating and in failure torque comparable with 2.3-mm titanium plating. Low-profile selfreinforced polylactide-polyglycolide and poly-L/DL-lactide miniplates provide satisfactory biomechanical stability for metacarpal fixation. These findings suggest that bioabsorbable miniplating can be used safely in the clinical stabilization of metacarpal and phalangeal fractures.

Absorbable Implants↗

Increased expression of a novel osteoclast-stimulating factor, ADAM8, in interface tissue around loosened hip prostheses.

OBJECTIVE: ADAM8 is a protein of a disintegrin and a metalloproteinase family that can induce osteoclast fusion and activity, perhaps via interactions involving integrin receptors and their cysteine-rich/disintegrin domains. Because loosening of hip replacement implants is characterized by foreign body giant cells and peri-implant osteoclasts, it was speculated that this molecule might be (over)expressed in the synovial membrane-like interface tissues. METHODS: In situ hybridization; immunohistochemical staining with or without tartrate-resistant acid phosphatase (TRAP) staining; image analysis/morphometry; isolation, amplification, and cloning of ADAM8; nucleotide sequencing; quantitative reverse transcriptase-polymerase chain reaction (RT-PCR); and Western blot. RESULTS: In situ hybridization disclosed ADAM8 mRNA in mono- and multinuclear cells in both interface and control synovial samples. Quantitative RT-PCR revealed high ADAM8 mRNA copy numbers in interface tissue (p < 0.01). Accordingly, extensive ADAM8 immunoreactivity was observed in the lining-like layers and sublining areas of interface tissue (p < 0.001). A 65 kDa ADAM8 band in Western blot of tissue extracts confirmed these findings. ADAM8/TRAP double staining showed close spatial relationships of ADAM8 positive precursor cells with other precursors and/or TRAP-positive multinuclear cells. CONCLUSION: ADAM8 is (over)expressed in tissues around aseptically loosened total hip implants, which are characterized by chronic foreign body inflammation and peri-implant bone loss. This is compatible with a role for ADAM8 in the formation of foreign body giant cells and osteoclasts.

Aged↗

Acidic cysteine endoproteinase cathepsin K in the degeneration of the superficial articular hyaline cartilage in osteoarthritis.

OBJECTIVE: To measure cartilage pH in patients with osteoarthritis (OA) and to analyze the presence of cathepsin K, the recently discovered acidic endoproteinase, in phenotypically altered chondrocytes. METHODS: Intraoperative measurements of the pH of clinically normal, fibrillated, superficially fissured, and deeply fissured cartilage surfaces (grades 0-3, respectively) in OA patients undergoing primary hip replacement surgery were performed with the use of a sting electrode sterilized with microbicidic plasma. Fluorescent pH probes were used for in situ assessment of cartilage matrix pH. Cathepsin K was assessed using quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry methods. RESULTS: The pH of grade 0 cartilage surfaces was 7.1 +/- 0.4 (mean +/- SD), compared with 6.2 +/- 0.9 (P < 0.05), 5.7 +/- 1.0 (P < 0.001), and 5.5 +/- 1.0 (P < 0.001) for grades 1-3 cartilage surfaces, respectively. Fluorescent pH probes and acid-dependent autocatalytic conversion of cathepsin K into its active, low molecular weight form in cartilage confirmed these findings. Cathepsin K messenger RNA levels increased in relation to the severity of OA, and the number of cathepsin K-containing chondrocytes increased from a mean +/- SD of 12 +/- 3 in grade 0 cartilage surfaces to 47 +/- 7, 50 +/- 6, and 100 +/- 12 in grades 1-3 cartilage surfaces, respectively (P < 0.001 for all comparisons). CONCLUSION: Acid-activated, but pharmacologically inhibitable, cathepsin K is induced in phenotypically altered chondrocytes in OA. The findings suggest that cathepsin K, rather than neutral matrix metalloproteinases, degrades the superficial gliding surfaces of the articular hyaline cartilage in OA.

Acids↗

Reciprocal age-related changes in GAP-43/B-50, substance P and calcitonin gene-related peptide (CGRP) expression in rat primary sensory neurones and their terminals in the dorsal horn of the spinal cord and subintima of the knee synovium.

Age-related changes in the expression of the growth associated protein GAP-43/B-50, and the neuropeptides substance P and calcitonin gene-related peptide (CGRP) were investigated in the sensory neurones of rat dorsal root ganglia, dorsal horns of the spinal cord and subintimal knee synovium. The two time-points studied were 2 months (young adults) and 14-month (aged)-old Sprague Dawley rats. Dorsal root ganglia: In young adults, 40 and 35% of the L4-L5 dorsal root ganglion neurones were positive for GAP-43/B-50 with a 1.5 fold increase in frequency in aged rats at the L5 ganglion. GAP-43/B-50 was strongly expressed by the non-neuronal satellite cells of some medium and many large sized neurones in aged rats. There were marked reciprocal shifts between small and medium sized sensory neurones in respect to their substance P and CGRP expression profiles. Dorsal horn of the spinal cord: there was a 1.3 fold decrease of substance P at L5 level and a 1.3 and 1.5 fold decrease of CGRP at L4-L5 levels in aged rats, respectively. Synovial membrane: There was a 2.3 fold increase in GAP-43/B-50 and a 2.5 fold decrease of CGRP with no changes in substance P expression. These results indicate that (i) primary sensory neurones undergo age-related changes already in early stages of aging, (ii) aging may result in a reduction of substance P and CGRP axonal transport, and (iii) reduced numbers of CGRP containing synovial perivascular fibres may imply a deficient regulation of the synovial microvasculature and therefore metabolic homeostasis of the joint in aged subjects.

Aging↗

Self-reinforced bioabsorbable versus metallic fixation systems for metacarpal and phalangeal fractures: a biomechanical study.

Bioabsorbable fixation devices offer a useful option to treat small bone fractures of the hand if the prerequisite of reliable and stable osteofixation is met. We compared the stabilities of various bioabsorbable fixation devices with metallic fixation devices by using an oblique osteotomy model in radial to ulnar orientation. The 1.5-mm, self-reinforced, poly-L-lactide (SR-PLLA) pins provided fixation rigidity comparable with 1.5-mm K-wires in dorsal and palmar apex bending, whereas in lateral apex bending and in torsion the rigidity was equal to that of 1.25-mm K-wires. The 2.0-mm, self-reinforced, poly-L/DL-lactide (SR-P(L/DL)LA) 70/30 screws provided rigidity comparable with that of 1.5-mm K-wires in all testing modes. The bioabsorbable plate considerably enhanced the bending stabilities of the fixation system, but a single interfragmentary screw provided only limited rotational rigidity. The results show that by using ultra-high strength self-reinforced implants adequate fixation stability for hand fracture fixation can be achieved.

Absorbable Implants↗

Bone stress injuries of the lower extremity: a review.

Bone stress injuries can cause long-lasting damage, especially in young athletes and military conscripts, if not diagnosed and treated properly. Diagnosis has been traditionally based on clinical, radiographic and scintigraphic examinations, but MRI has become increasingly important. High resolution MRI is particularly valuable for the grading of bone stress injuries. The clinician should be aware of the wide range of bone stress injuries and available diagnostic methods. Early diagnosis is the prerequisite for avoiding long-lasting complications. Most bone stress injuries heal with closed treatment, but surgery is necessary in some cases. They heal well if the diagnosis is not delayed and the treatment adequate.

Adult↗

Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients.

BACKGROUND: The treatment of open fractures of the tibial shaft is often complicated by delayed union and nonunion. The objective of this study was to evaluate the safety and efficacy of the use of recombinant human bone morphogenetic protein-2 (rhBMP-2; dibotermin alfa) to accelerate healing of open tibial shaft fractures and to reduce the need for secondary intervention. METHODS: In a prospective, randomized, controlled, single-blind study, 450 patients with an open tibial fracture were randomized to receive either the standard of care (intramedullary nail fixation and routine soft-tissue management [the control group]), the standard of care and an implant containing 0.75 mg/mL of rhBMP-2 (total dose of 6 mg), or the standard of care and an implant containing 1.50 mg/mL of rhBMP-2 (total dose of 12 mg). The rhBMP-2 implant (rhBMP-2 applied to an absorbable collagen sponge) was placed over the fracture at the time of definitive wound closure. Randomization was stratified by the severity of the open wound. The primary outcome measure was the proportion of patients requiring secondary intervention because of delayed union or nonunion within twelve months postoperatively. RESULTS: Four hundred and twenty-one (94%) of the patients were available for the twelve-month follow-up. The 1.50-mg/mL rhBMP-2 group had a 44% reduction in the risk of failure (i.e., secondary intervention because of delayed union; relative risk = 0.56; 95% confidence interval = 0.40 to 0.78; pairwise p = 0.0005), significantly fewer invasive interventions (e.g., bone-grafting and nail exchange; p = 0.0264), and significantly faster fracture-healing (p = 0.0022) than did the control patients. Significantly more patients treated with 1.50 mg/mL of rhBMP-2 had healing of the fracture at the postoperative visits from ten weeks through twelve months (p = 0.0008). Compared with the control patients, those treated with 1.50 mg/mL of rhBMP-2 also had significantly fewer hardware failures (p = 0.0174), fewer infections (in association with Gustilo-Anderson type-III injuries; p = 0.0219), and faster wound-healing (83% compared with 65% had wound-healing at six weeks; p =0.0010). CONCLUSIONS: The rhBMP-2 implant was safe and, when 1.50 mg/mL was used, significantly superior to the standard of care in reducing the frequency of secondary interventions and the overall invasiveness of the procedures, accelerating fracture and wound-healing, and reducing the infection rate in patients with an open fracture of the tibia.

Adolescent↗

Dense innervation in pseudocapsular tissue compared to aneural interface tissue in loose totally replaced hips.

BACKGROUND: The function of many inflammatory cells is in part regulated by neuronal cells, which may lead to so-called neurogenic inflammation. Sensory nerves also mediate the pain sensation. METHODS: This immunohistochemical study focused on visualization of C-sensory and sympathetic innervation in the synovial membrane-like interface and pseudocapsular tissue around loosened total hip replacement. RESULTS: The synovial membrane-like interface did not contain C-sensory peptidergic or sympathetic neural structures. Only limited attempts to neural regeneration were detected. In contrast, pseudocapsule expressed dense innervation with strong CPON-ir sympathetic innervation and osteoarthritis also had C-sensory fibers. Intense neural regeneration was seen in these synovial membranes. Surprisingly, stellate and/or highly dendritic fibroblast-like cells in the fibrotic areas in the interface tissue expressed strong immunoreactivity to the neural marker PGP 9.5, ubiquitin carboxyterminal hydrolase. CONCLUSION: Pain related to aseptic loosening cannot arise in the aneural interface membrane. Inflammation in interface/aseptic loosening seems to be driven by non-neurogenic factors, such as foreign bodies and micromovement. Insufficient lysosomal degradation of denatured proteins causes accumulation of ubiquitinated conjugates and enzymes involved in the process. This leads to insufficient degradation of platelet derived growth factor (PDGF)-receptor complex and can contribute to the accumulation of connective tissue in the interface. Failure in ubiquitin mediated proteolysis might support overgrowth of interface tissue and aseptic loosening.

Adrenergic Fibers↗

Cellular fibronectin in failing dental implants.

PURPOSE: Cellular fibronectin staining is decreased in adult periodontitis, which implies elastase-mediated degradation of periodontal tissues. The purpose of this study was to determine whether failing dental implants display similar changes. MATERIALS AND METHODS: Cellular fibronectin and its integrin receptors were identified by immunohistochemistry and quantified by computerized image analysis. RESULTS: Cellular fibronectin was found in blood vessel walls, epithelial basement membranes, and fibroblasts. Quantitative results of cellular fibronectin staining were as follows: failing dental implants, median 26.5% (Q3-Q1 = 23%); adult periodontitis, median 5.5% (Q3-Q1 = 5.6%); normal controls, median 12.2% (Q3-Q1 = 7.5%). Cellular fibronectin staining was increased around failing dental implants but decreased in adult periodontitis compared to healthy controls. DISCUSSION: The distribution of integrin receptor subunits alpha4, alpha5, and beta1 of cellular fibronectin was similar in failing dental implants. The pathomechanisms in adult periodontitis and failing dental implants seem to differ. CONCLUSIONS: Adult periodontitis is characterized by proteolysis/loss of cellular fibronectin, whereas failing dental implants are characterized by increased cellular fibronectin deposition, probably as a result of titanium-induced local synthesis and relatively modest degradation.

Adolescent↗