Knee arthrodesis with the Ilizarov external fixator as treatment for septic failure of knee arthroplasty.

BACKGROUND: The authors report the results of femoral-tibial fusion with an Ilizarov circular external fixator following septic loosening of knee prosthesis. MATERIALS AND METHODS: The series included 17 patients with a mean age of 62.9 years, treated from 1990 to 2007 with femoral-tibial fusion. The Cierny-Mader classification was used for clinical and anatomopathological evaluation; the Engh classification was used to assess the bone defect. Surgical treatment differed according to these criteria. RESULTS: Healing was achieved in 13 out of 17 patients at the first surgical attempt in a mean time of 9.3 months. Mean follow-up was 30 months. Of the four complications, two patients had an intolerance to the external fixator that led to its early removal, and the other two had a septic intraarticular nonunion. CONCLUSIONS: The Ilizarov circular external fixator is a very reliable fixation system due to its low cost, versatility, stability under load, and low risk of septic dissemination. Nevertheless, an appropriate patient selection and a good surgeon's experience are necessary.

Interferon-alpha inhibits in vitro osteoclast differentiation and renal cell carcinoma-induced angiogenesis.

Bone is a common site of osteolytic and richly vascularized metastases of renal cell carcinoma (RCC) and Interferon (IFN)-alpha based therapies have been considered for the treatment of patients affected by this disease. The effects of IFN-alpha on metastatic RCC patients have been related to its immunomodulatory, and cytotoxic activity on tumor cells, but there could be an effect also on tumor induced osteoclast differentiation and bone angiogenesis. When osteoclasts obtained from human peripheral blood mononuclear cells, cultured in the presence of receptor activator of nuclear factor-kappaB (RANKL) and macrophage-colony stimulating factor (M-CSF), were treated with IFN-alpha, the expression of bone tartrate resistant acid phosphatase (TRACP) type 5b was reduced, as well as calcium-phosphate resorption activity and expression of pro-osteoclatic transcription factor c-Fos. IFN-alpha modulation of angiogenesis was studied by analysis of proliferation, survival, and migration of a bone endothelial cell line (BBE), and by the analysis of pro-angiogenic factor expression in RCC cell lines. IFN-alpha inhibited bone endothelial cell proliferation and the expression of FGF-2, while the vascular endothelial growth (VEGF) did not show any significant variation. Moreover, IFN-alpha inhibited the migration induced by the RCC through the impairment of fibroblast growth factor-2 (FGF-2) secretion. These data demonstrate multiple activities of IFN-alpha on renal cancer-induced bone disease, in addition to its recognized role as a cytotoxic and immunomodulatory agent, because they indicate its ability to reduce bone resorption and to impair tumor-associated angiogenesis, and they also suggest the use of IFN-alpha to treat skeletal metastases of other carcinomas.

Human bone marrow stromal cells: In vitro expansion and differentiation for bone engineering.

Stromal cells from marrow hold a great promise for bone regeneration. Even if they are already being exploited in many clinical settings, the biological basis for the source and maintenance of their proliferation/differentiation potential after in vitro isolation and expansion needs further investigation. Most studies on osteogenic differentiation of marrow stromal cells (MSC) have been performed using bone marrow from the iliac crest. In this study, MSC were derived from spare femoral bone marrow obtained during hip replacement surgery from 20 adult donors. After in vitro isolation the cells were grown in osteogenic medium, and their proliferation and differentiation analysed during in vitro expansion. We found that MSC isolated from the femur of adult patients consistently maintain an osteogenic potential. Using biochemical signals, these cells turn to fully differentiated osteoblasts with a predictable set of molecular and phenotypic events of in vitro bone deposition. When seeded on polycaprolactone-based scaffold or surfaces, the proliferation and mineralization of femur-derived MSC were modulated by the surface chemistry/topography. Despite remarkable differences between individual colony-forming ability, alkaline phosphatase production, and mineralization ability, these cells are a potential source for bone engineering, either by direct autologous reimplantation or by ex vivo expansion and reimplantation combined to a proper scaffold.

In vivo study on the healing of bone defects treated with bone marrow stromal cells, platelet-rich plasma, and freeze-dried bone allografts, alone and in combination.

The repair of confined trabecular bone defects in rabbits treated by autologous bone marrow stromal cells (BMSC), platelet-rich plasma (PRP), freeze-dried bone allografts (FDBA) alone and in combination (BMSC + PRP; FDBA + BMSC; FDBA + PRP; FDBA + PRP + BMSC) was compared. A critical size defect was created in the distal part of the femurs of 48 adult rabbits. Histology and histomorphometry were used in the evaluation of healing at 2, 4, and 12 weeks after surgery. The healing rate (%) was calculated by measuring the residual bone defect area. Architecture of the newly formed bone was compared with that of bone at the same distal femur area of healthy rabbits. The defect healing rate was higher in PRP + BMSC, FDBA + PRP, FDBA + BMSC, and FDBA + PRP + BMSC treatments, while lower values were achieved with PRP treatment at all experimental times. The highest bone-healing rate at 2 weeks was achieved with FDBA + PRP + BMSC treatment, which resulted significantly different from PRP (p < 0.05) and BMSC (p < 0.05) treatments. At 4 weeks, the bone-healing rate increased except for PRP treatment. Finally, the bone-healing rate of FDBA + PRP, FDBA + BMSC, and FDBA + PRP + BMSC was significantly higher than that of PRP at 12 weeks (p < 0.05). At 12 weeks, significant differences still existed between PRP, BMSC, and FDBA groups and normal bone (p < 0.05). These results showed that the combination of FDBA, BMSC and PRP permitted an acceleration in bone healing and bone remodeling processes.

Poly-epsilon-caprolactone/hydroxyapatite composites for bone regeneration: in vitro characterization and human osteoblast response.

Polycaprolactone (PCL), a semicrystalline linear resorbable aliphatic polyester, is a good candidate as a scaffold for bone tissue engineering, due to its biocompatibility and biodegradability. However, the poor mechanical properties of PCL impair its use as scaffold for hard tissue regeneration, unless mechanical reinforcement is provided. To enhance mechanical properties and promote osteoconductivity, hydroxyapatite (HA) particles were added to the PCL matrix: three PCL-based composites with different volume ratio of HA (13%, 20%, and 32%) were studied. Mechanical properties and structure were analysed, along with biocompatibility and osteoconductivity. The addition of HA particles (in particular in the range of 20% and 32%) led to a significant improvement in mechanical performance (e.g., elastic modulus) of scaffold. Saos-2 cells and osteoblasts from human trabecular bone (hOB) retrieved during total hip replacement surgery were seeded onto 3D PCL samples for 1-4 weeks. Following the assessment of cell viability, proliferation, morphology, and ALP release, HA-loaded PCL was found to improve osteoconduction compared to the PCL alone. The results indicated that PCL represents a potential candidate as an efficient substrate for bone substitution through an accurate balance between structural/ mechanical properties of polymer and biological activities.

Differences in ion release after ceramic-on-ceramic and metal-on-metal total hip replacement. Medium-term follow-up.

Modern metal-on-metal bearings produce less wear debris and osteolysis, but have the potential adverse effect of release of ions. Improved ceramic-on-ceramic bearings have the lowest wear of all, but the corrosion process has not been analysed. Our aim was to measure the serum ion release (ng/ml) in 23 patients having stable hip prostheses with a ceramic-on-ceramic coupling (group A) and to compare it with the release in 42 patients with a metal-on-metal bearing (group B) in the medium term. Reference values were obtained from a population of 47 healthy subjects (group C). The concentrations of chromium, cobalt, aluminium and titanium were measured. There was a significant increase of cobalt, chromium and aluminium levels (p < 0.05) in group B compared with groups A and C. Group A did not differ significantly from the control group. Despite the apparent advantage of a metal-on-metal coupling, especially in younger patients with a long life expectancy, a major concern arises regarding the extent and duration of ion exposure. For this reason, the low corrosion level in a ceramic-on-ceramic coupling could be advantageous.

Evaluation of bone healing enhancement by lyophilized bone grafts supplemented with platelet gel: a standardized methodology in patients with tibial osteotomy for genu varus.

Orthopedic practice may be adversely affected by an inadequate bone repair that might compromise the success of surgery. In recent years, new approaches have been sought to improve bone healing by accelerating the rate of new bone formation and the maturation of the matrix. There is currently great interest in procedures involving the use of platelet gel (PG) to improve tissue healing, with satisfactory results both in vitro and in maxillofacial surgery. Otherwise, to our knowledge, only a preliminary clinical study was undertaken in the orthopedic field [Kitoh et al., Bone 2004;35:892-898] and the efficacy of PG is still controversial. Our paper focuses on the effect on bone regeneration by adding PG to lyophilized bone chips used for orthopedic applications. The clinical model and the laboratory methodology were standardized. As a clinical model, we employed the first series of patients of a randomized case-control study undergoing high tibial osteotomy (HTO) for genu varus. Ten subjects were enrolled: in 5 patients lyophilized bone chips supplemented with PG were inserted during tibial osteotomy (group A); 5 patients were used as a control (group B) and lyophilized bone chips without gel were applied. Forty-five days after surgery, computed tomography scan guided biopsies of grafted areas were obtained and the bone maturation was evaluated by a standardized methodology: the osteogenic and angiogenic processes were semi-quantitatively characterized by using histomorphometry, and the mineral component of the lyophilized and host bone was analyzed by using X-ray diffraction technique with sample microfocusing and microradiography. Lyophilized bone with PG seems to accelerate the healing process, as shown by new vessel formation and deposition of newly formed bone, with no evidence of inflammatory cell infiltrate, when compared with lyophilized bone without gel. On the contrary, lyophilized bone undergo a resorption process, and a fibrous tissue often fills the spaces between chips. A histiocytic/giant-cell reaction is sometimes present. Otherwise, no differences have been found concerning microstructure. Our findings show the reliability of the methodology used to monitor early bone repair. The completion of the study and the evaluation of the ultimate clinical outcome are necessary in order to verify PG in vivo effects in orthopedic surgery.

Effects of activated platelet concentrates on human primary cultures of fibroblasts and osteoblasts.

BACKGROUND: Platelet alpha granules contain growth factors released into the surrounding environment during activation. This property has been used in clinical medicine to accelerate the repair process by activating in vitro autologous platelets with thrombin and has also been proposed to promote the proliferation of bone cells. The aim of this research was to assess the effect of platelet concentrates activated with thrombin on human gingival fibroblasts and human osteoblasts from trabecular bone. METHODS: Platelet concentrates, activated with bovine thrombin, were added to the cells in serum-free medium. The cultures were assessed for proliferation by vital stain and cell count after 72-hour incubation. Alkaline phosphatase activity was tested after 72-hour incubation on the osteoblast lysates by a colorimetric assay. After 21 days the formation of mineral nodules was tested in the osteoblast cultures by alizarin red staining. The effects of the activated platelet concentrates (APC) were compared with the serum-free medium (SF), or with platelet-poor plasma added medium (PPP). RESULTS: The fibroblast growth in the presence of APC was higher, though not significantly, than SF. APC resulted in a nonsignificant decrease in proliferation and alkaline phosphatase expression in osteoblasts, compared both to serum free medium, and PPP. Mineralization was only modestly increased after incubation with APC in comparison with serum-free medium. CONCLUSIONS: There were no statistical differences in fibroblast proliferation, or in osteoblast growth and functions between serum-free conditions and the platelet gel treatment. Therefore, neither fibroblast proliferation nor osteoblast growth and functions were affected by the activated platelet concentrates in vitro.

Systemic cross-linked N-terminal telopeptide and procollagen I C-terminal extension peptide as markers of bone turnover after total hip arthroplasty.

There is no diagnostic, non-invasive method for the early detection of loosening after total hip arthroplasty. In a pilot study, we have analysed two serum markers of bone remodelling, procollagen I C-terminal extension peptide (PICP) and cross-linked N-terminal telopeptide (NTx), as well as the diagnostic performance of NTx for the assessment of osteolysis. We recruited 21 patients with loosening (group I), 18 with a well-fixed prosthesis (group II) and 17 at the time of primary arthroplasty for osteoarthritis (OA) (group III). Internal normal reference ranges were obtained from 30 healthy subjects (group IV). The serum PICP level was found to be significantly lower in patients with OA and those with loosening, when compared with those with stable implants, while the NTx level was significantly increased only in the group with loosening, suggesting that collagen degradation depended on the altered bone turnover induced by the implant. This hypothesis was reinforced by the finding that the values in the pre-surgery patients and stable subjects were comparable with the reference range of younger healthy subjects.A high specificity and positive predictive value for NTx provided good diagnostic evidence of agreement between the test and the clinical and radiological evaluations. The NTx level could be used to indicate stability of the implant. However, further prospective, larger studies are necessary.

Bone with cement and antibiotic: antibiotic release in vitro.

It was the purpose of the study to evaluate morcellized bone with cement and antibiotic release mixed with vancomycin and methylmethacrylate cement (PMMA). The aim of the study is part of a wider one aimed at verifying the possibility of using this composite for the treatment of chronic septic pathologies of the bone. Five cylinders 1 cm in height by 1 cm in diameter, formed by morcellized bone with cement and vancomycin were immersed in plasma and 5 in physiological solution. Three cylinders equal in size but formed by cement and antibiotic alone were immersed in plasma and 3 in physiological solution. All of the cylinders remained in immersion for 28 days at a temperature of 37 degrees C. The immersion fluids were changed every day during the first week and on days 14, 21 and 28. The quantity of vancomycin released was dosed in each specimen. The greatest and most constant release of antibiotic took place in the cylinders of morcellized bone, cement and antibiotic immersed in plasma.

Adamantinoma of the long bones. The experience at the Istituto Ortopedico Rizzoli.

All cases of adamantinoma seen at the Istituto Ortopedico Rizzoli were retrospectively reviewed. Although this tumor is exceedingly rare, nine cases were collected. The tumor is composed of four histological patterns: spindle, basaloid, squamoid, and tubular. The prognosis of this tumor depends on the adequacy of therapy. Surgery that is expedient and adequate tends to offer the best prognosis.

In vitro testing of the potential for orthopedic bone cements to cause apoptosis of osteoblast-like cells.

The purpose of this study was to investigate in vitro the apoptosis- and/or necrosis-inducing potential of polymethylmethacrylate (PMMA)-based bone cements for prosthetic surgery. Four bone cements widely used in orthopedics were tested as extracts onto osteoblast-like MG-63 cells and for comparison, HL-60 cells, which are remarkably sensitive to apoptotic stimuli. Neutral red uptake (NRU) was used to measure cell viability while Hoechst 33258 staining was used to detect DNA content. Apoptosis was characterized using a BrdU-based ELISA assay for DNA fragmentation and examined by fluorescence microscopy using acridine orange and propidium iodide staining of nuclei. The generation of reactive oxygen species (ROS), which could mediate apoptosis, was verified using dichlorofluorescein-diacetate (DCFH-DA) oxidation to DCF. After 24 h of challenge of the cells with the four cement extracts, the viability of either MG-63 or HL-60 cells was found to be unaltered, as recorded by NRU. Apoptotic cell death was induced by three cements in HL-60, whereas MG-63 cells were significantly affected by the four cements tested: the finding of DNA fragments both in the cytoplasm and supernatants of MG-63 after 24 h demonstrated that these cells underwent late-apoptosis secondary necrosis. Fluorescent staining of the nuclei confirmed the results obtained with the ELISA test. Oxygen free radicals were elicited by two cements in HL-60 cells, while MG-63 did not generate ROS in response to cements. This study helps to gain more insight into the mechanism of cell death induced by PMMA-based cements and suggests apoptosis of osteoblasts as a part of the tissue reaction around cemented prostheses.

Expression of the CD69 activation antigen on lymphocytes of patients with hip prosthesis.

The aim of the study was to evaluate the sensitization to metals in patients with Co-Cr hip prosthesis. Peripheral blood mononuclear cells (PBMC) were collected from 14 healthy donors and three groups of patients: 10 candidates for primary total joint replacements, 11 patients with well-fixed implant and 13 patients with aseptic loosening of the hip prosthesis. PBMCs were cultured with the metal ions employed for implant manufacturing and the expression of CD69 activation antigen on CD3/T lymphocytes was detected by flow cytometry. Chromium extract increased significantly the expression of CD3/CD69 phenotype in patients with loosening of hip prosthesis. The chromium-induced 'activation index' was higher in patients with loosening of hip prosthesis than in healthy donors and in pre-implant patients. The cobalt-stimulated PBMC of patients with either well-fixed or loosened prosthesis had an 'activation index' significantly higher than healthy donors. The activation index values were used to graduate the PBMC-response as 'normal' (> or = 0.9 and < 2), 'low' (< 0.9) and 'high' (> or = 2): an high-activation index was observed only in chromium-exposed PBMC of patients with prosthesis. Our data show that chromium released from orthopedic implants could be responsible for the lymphocyte sensitization and flow cytometry is an easy and reliable method for monitoring the hypersensitivity state in patients with metal prostheses. Activated lymphocytes in the peri-implant tissue are likely to elicit a localized immune response and contribute to maintain the inflammatory process evolving in the implant failure.

Microradiographic and histochemical evaluation of mineralization inhibition at the bone-alumina interface.

Microradiographic and histochemical tests were used to examine the behaviour of the bone tissue close to the alumina coating in cementless hip prostheses which were radiologically stable and explanted because of pain. The presence was detected of a decalcification stripe of the bone tissue with a thickness of about 300 microns, parallel to the prosthesis profile and in appearance not influenced by the roughness of the surface. This phenomenon was attributed to the presence of aluminium ions similarly to what happens in osteomalacic osteodystrophy in nephropathic dialysed patients. It was concluded that the phenomenon must be carefully considered because, in the long term, it could cause failure in the alumina coating.

Ability of restorative and fluoride releasing materials to prevent marginal dentine demineralization.

The study aimed to define the in vitro secondary caries inhibiting potential of restorative materials currently used in dental practice. Class V restorations were prepared in extracted human third molars and immersed in a demineralizing solution (lactic acid, pH 4.5) at 37 degrees C for 2 days to simulate secondary caries formation. The bonding and the restorative systems tested in the study were: Scotchbond 1+Z 250 (Group A), Scotchbond 1+F 2000 (Group B), ABF+APX (Group C), ABF+F2000 (Group D). Perimarginal dentine, immediately close to the margin of the restoration, and exposed dentine, at approximately 0.5 mm from the margins of the restoration, after exposure to the acid solution, were investigated; protected dentine, at approximately 4 mm from the margin in a varnish-covered area, was analysed as control. Polarized light microscopy and contact transverse microradiography (TMR) were employed. The output parameters were lesion shape and size (depth in microm) of the exposed dentine, dentine mineral volume%, and integrated mineral loss (Delta Z, in %volmicrom) of the lesions. Compomers (Groups B and D) showed a thinner demineralization of the outer lesions, a less demineralization along the perimarginal dentine (inner lesion) and more caries inhibition zones or CIZs (Delta Z positive values) compared to composites (Groups A and C). In conclusion, Groups B and D materials seemed to partially counteract the marginal demineralization induced by an acid solution and favourably influence the formation of CIZs along the restorations. On the contrary, composites did not show a protective effect, probably due to an insufficient marginal seal and the lack of fluoride release.

Osteoblast growth and function in porous poly epsilon -caprolactone matrices for bone repair: a preliminary study.

Current methods for the replacement of skeletal tissue involve the use of autografts, allografts and, recently, synthetic substitutes, which provide a proper amount of material to repair large bone defects. Engineered bone seems a promising approach, but a number of variables have to be set prior to any clinical application. In this study, four different poly caprolactone-based polymers (PCL) were prepared and tested in vitro using osteoblast-like Saos-2 cells. Differences among three-dimensional polymers include porosity, addition of hydroxyapatite (HA) particles, and treatment with simulated body fluid. Biochemical parameters to assess cell/material interactions include viability, growth, alkaline phosphatase release, and mineralization of osteoblastic cells seeded onto three-dimensional samples, while their morphology was observed using light microscopy and SEM. Preliminary results show that the polymers, though degrading in the medium, have a positive interaction with cells, as they support cell growth and functions. In the short-term culture (3-7 days) of Saos-2 on polymers, little differences were found among PCL samples, with the presence of HA moderately improving the number of cells onto the surfaces. In the long term (3-4 weeks), it was found that the HA-added polymers obtained the best colonization by cells, and more mineral formation was observed after coating with SBF. It can be concluded that PCL is a promising material for three-dimensional scaffold for bone formation, and the presence of bone-like components improves osteoblast activity.

The influence of alumina and ultra-high molecular weight polyethylene particles on osteoblast-osteoclast cooperation.

Particle-induced macrophage activation, mainly by UHMWPE wear, has been recognized as the biological mechanism leading to periprosthetic bone resorption, which is responsible for the loosening of the total hip replacements (THR). Ceramic-on-ceramic implants have been advocated as a means of reducing wear products. Many studies investigated the effect of alumina (Al(2)O(3)) particles on monocytes/macrophages, but only limited information are available on their participation to bone turnover. An in vitro model was performed to investigate how Al(2)O(3) and UHMWPE particles may influence the osteoblast-osteoclast interaction: human osteoblasts (HOB) were obtained from trabecular bone, while osteoclasts were derived from peripheral blood mononuclear cells (PBMC) of healthy donors. The amount of IL6, TNF alpha, GM-CSF, and other factors acting on the bone turnover, i.e. the 'receptor activator of NF kappa B' ligand (RANKL) and osteoprotegerin (OPG), was detected in culture medium of particle-challenged HOB (HOB-CM). The Al(2)O(3) and UHMWPE particles did not affect either cell viability or TNF and GM-CSF release, while the increase in IL6 release seemed to be dependent on the particle concentration. UHMWPE increased the release of RANKL from HOB, while OPG and OPG-to-RANKL ratio were significantly inhibited. The ability of HOB-CM to promote osteoclastogenesis was tested via osteoblast/monocyte cooperation: after seven days of culture UHMWPE HOB-CM induced a large amount of multinucleated TRAP-positive giant cells, as well as significantly reduced the amount of IL6, GM-CSF and RANKL in the supernatant. With regard to the inductive effect on the osteoclastogenesis, our results show that the Al(2)O(3) wear debris are less active.

Biomechanical and histomorphometric investigations on two morphologically differing titanium surfaces with and without fluorohydroxyapatite coating: an experimental study in sheep tibiae.

The influence of fluorohydroxyapatite (FHA) coating and surface roughness of Ti6Al4V implants on bone response was investigated. Uncoated and FHA-coated screws with lower (LR and LR+FHA; Ra: 5.7+/-0.2 microm) and higher (HR and HR+FHA; Ra: 21.8+/-0.9 microm) surface roughness, were inserted into the diaphyses of 8 sheep tibiae. Twelve weeks after implantation, extraction torque and bone-to-implant contact were evaluated. The smoothest surfaces showed an improved extraction torque and significant differences were observed between LR and HR (-24.6%, p<0.0005), LR and HR+FHA (-30.7%, p<0.0005), LR+FHA and HR (-17.4%, p<0.005), and LR+FHA and HR+FHA (-24.0%, p<0.005). The bone-to-implant contact data paralleled the biomechanical data: the smoother the surface, the greater the bone-to-implant contact. Significant (p<0.0005) decreases in bone-to-implant contact were observed between LR+FHA and HR (-24.2%), and between LR+FHA and HR+FHA (-29.2%). The current findings suggest that LR surfaces significantly improve the osteointegration rate of implanted cortical screws independently of the FHA coating.

Ion release in stable hip arthroplasties using metal-on-metal articulating surfaces: a comparison between short- and medium-term results.

The use of metallic heads articulating with metallic cups could solve the problem of polyethylene (PE) wear in total hip replacement (THR) with metal-on-PE bearings. A conspicuous release of metal ions from new models of metal-on-metal bearings has been found in the short-term, but it is yet unclear whether the medium-term corrosion rate is high or, on the contrary, it becomes negligible, because of the continuous surface finishing. Our purpose was to compare the serum ion values (nanograms per milliliter) in 15 patients with metal-on-metal stable prosthesis (Group A), in the short-term (subgroup A(1); mean follow-up: 24 mo) and medium-term (subgroup A(2); mean follow-up: 52 mo), in order to determine whether the ion release decreased with time of implant. Chromium (Cr), cobalt (Co), molybdenum (Mo) and aluminum (Al) were analyzed. Twenty-two presurgical patients were used for comparison (Group B). The reference range was obtained from a population of 27 healthy subjects (Group C). Co and Cr levels in the medium-term (subgroup A(2)) were not decreased in comparison with the short-term values (subgroup A(1)) and were significantly higher (p < 0.001) than presurgical and reference values. Otherwise, Mo and Al concentrations were not significantly increased in comparison with reference values. In conclusion, despite the apparent advantage of metal-on-metal coupling, especially in younger patient populations, there is a major concern about the extent and duration of the relevant "internal" exposure to Cr and Co ions. This exposure should be carefully monitored, in order to clarify the biologic effects of ion dissemination and, consequently, to identify risks concerning long-term toxicity of metals.

Biologic effects of surface roughness and fluorhydroxyapatite coating on osteointegration in external fixation systems: an in vivo experimental study.

The concomitant influence of surface roughness and fluorhydroxyapatite (FHA) coating of titanium (Ti) implants on bone response was investigated. For this purpose, titanium screw-shaped implants with a lower degree (Y371) and a higher degree (TiPore300) of surface roughness, coated with FHA and uncoated, were transversally inserted into the diaphyses of sheep tibiae for 12 weeks. Four sheep received Y371 (group A) and Y371 + FHA (group B) screws and four sheep received TiPore300 (group C) and TiPore300 + FHA (group D) screws. For each type of material, the morphology and microstructure of implant-facing bone were evaluated. The host bone of each tibia was used as a control. In all groups the bone tissue did not reach a complete maturation. The higher degree of roughness, perhaps due to an excessive irregularity of the surface, induced the worst osteointegration: a fibrous tissue layer between screw and new bone tissue was often present. Nevertheless, as viewed by XRD, no crystallographic change of the apatite lattice was observed in any of the implants. In contrast, the microhardness value, an index of bone mineralization, was higher in the uncoated screws and decreased progressively in the following order: group C > group A > group B > group D. The association of plasma spraying with roughness treatment constitutes a complex system that seems to interfere with bone mineralization. A chemical change of the surface, perhaps with more Ti release or more coating degradation, could be responsible for such impairment. The authors emphasize the necessity for simultaneous evaluation of surface topography and chemistry as well as an improvement in plasma-spraying and post-processing techniques and in standard procedures for materials characterization.