Interactions of human bone cells with diamond-like carbon polymer hybrid coatings.

Diamond-like carbon (DLC) coatings produced using the plasma-accelerating filtered pulsed arc discharge (FPAD) method display excellent adherence to the substrate and improve its corrosion resistance. This article reports the interactions of human osteoblastic cells with DLC and two DLC polymer hybrid (DLC-p-h) coatings deposited on smooth, matt and rough silicon wafers by the FPAD method. The DLC-p-h materials were DLC-polytetrafluoroethylene hybrid (DLC-PTFE-h) and DLC-polydimethylsiloxane hybrid (DLC-PDMS-h) coatings. The biocompatibility of the coatings was assayed by using mesenchymal stem cells, primary osteoblasts and Saos-2 cells. Human mesenchymal stem cells proliferated when cultured on DLC and DLC-PTFE-h, but their numbers diminished on DLC-PDMS-h. In all three cell types studied, phalloidin-TRITC staining disclosed cell-type organization typical of an actin cytoskeleton on DLC and DLC-PTFE-h, but minimal and disorganized stress fibers on cells cultured on DLC-PDMS-h. The microtubular cytoskeleton was similarly disorganized on DLC-PDMS-h. Cells on DLC-PDMS-h developed a peculiar form of membrane damage, with nuclear staining by propidium iodide associated with granular calcein staining of the cytoplasm. Active caspase-3 labeling was only seen in cells cultured on DLC-PDMS-h, indicating that these cells undergo apoptosis induced by defective cell adhesion. Results suggest that DLC-PDMS-h coatings might be useful in orthopedic applications where an implant or implant-facet should be protected against bone overgrowth while DLC and DLC-PTFE-h coatings might improve osseointegration.

Proximal humerus fracture rotational stability after fixation using a locking plate or a fixed-angle locked nail: the role of implant stiffness.

BACKGROUND: Fixed-angle locked devices have been developed to improve internal fixation of proximal humerus fractures. Available low-profile precontoured locking plates and intramedullary nails with fixed-angle interlocks are currently favored by most surgeons in this setting. The aim of this study was to assess the relative stability of these two methods of fixation under torsion load. METHODS: A surgical neck osteotomy was created in six pairs of embalmed humeri. In each pair, one specimen was secured with a titanium locking-compression plate, and the contralateral was secured with a titanium nail with a proximal locked spiral blade. The specimens were first tested cyclically in internal-external rotation for 10,000 cycles to evaluate interfragmentary motion (dynamic study). At the end of the cyclic testing, the specimens were loaded to failure in external rotation to measure torque to failure and construct stiffness (static study). FINDINGS: There were no significant differences in interfragmentary motion between the two fixation devices in the dynamic study. When tested to failure, fixation with the locking plate tolerated on average 20 more degrees in torsion before failure, and demonstrated higher torsional load to failure and less torsional stiffness (P<0.05). INTERPRETATION: Both locking plates and locked intramedullary nails may provide enough stability to avoid secondary displacement of proximal humerus fractures during early physical therapy. Locking plates demonstrated superior biomechanical properties under high rotational loads than locked intramedullary nails in a cadaveric proximal humerus two-part osteotomy model, and could provide more protection against unexpected high torsion loads.

Using metal-ligand interactions for the synthesis of metallostar polymers.

In this work we report the synthesis and assembly of metallostar polymers using a combination of metal complexation, RAFT and Click chemistry.

Interventions to improve inpatient osteoporosis management following first osteoporotic fracture: the PREVENT project.

OBJECTIVES: To establish a protocol for the treatment of fragility fractures in the hospital setting based on treatment of osteoporosis. MATERIALS AND METHODS: An intervention protocol was implemented in patients with fragility fractures based on (1) indicating the diagnosis of osteoporotic fracture in the summary of discharge; (2) "lifestyle recommendations"; and (3) therapy for osteoporosis. Thirty-one hospitals were involved and they were informed of the importance of protocol compliance. In the first phase, a retrospective study was conducted to establish the number of low-energy fractures treated and the percentage of them that had complied with the protocol (n = 887). Then, prospectively, the same data were collected for the patients managed for 1 year (n = 6,826) in three sections of 4-month intervals. RESULTS: The percentage of compliance increased from 8.2 to 57.2% in the first point, from 12.6 to 42.4% in the second, and from 10.3 to 43.2% in the third. CONCLUSION: The implementation of programs to improve osteoporosis treatment is very useful for ensuring adherence in the management of osteoporosis following admission due to fragility fracture.

Update on UHMWPE research: from the bench to the bedside.

Ultra-high molecular weight polyethylene (UHMWPE) is the key material for achieving excellent long-term results in total joint arthroplasties. Despite the fact that there has been a substantial amount of research and development over the years, new aspects of this material are still controversial and the most recent innovations have had a variable reception regarding clinical use. Advancements in conventional UHMWPE in the 1990s (nitrogen atmosphere irradiation, barrier package) were further improved by introduction of first-generation crosslinked polyethylene, as seen both from laboratory findings and clinical results. However, while clinical data on first-generation highly crosslinked polyethylene (HXLPE) showed reduced wear in the medium-term, academic and industrial research have helped to refine the material further, to overcome criticisms regarding residual oxidation and potential material fracture. Present concerns, although less nowadays, relate to the post-irradiation techniques used to stabilize the crosslinked polyethylene, namely annealing and remelting. Current topics of research interest include in vivo oxidation, second-generation highly crosslinked polyethylene, vitamin E doped or blended polyethylene, fracture mechanics, and consequences of wear. Some of these improvements derived from recent research are already available to the orthopedic community, and others will appear in the next few years. This review gives an overview of these topics, and the latest advancements are described in detail with a view to help the orthopedic surgeon make scientifically sound decisions when selecting material for total-joint implants. We conclude the review by affirming that today's state-of-the-art material is no longer conventional UHMWPE, but HXLPE.1.

Modulation of the cross-talk between macrophages and osteoblasts by titanium-based particles.

Titanium (Ti) and its alloys have widespread uses as implant materials for orthopaedic and dental applications. To improve their surface characteristics, modifications that give rise to an outer ceramic layer of rutile have been developed. It is expected that after a long period of service, rutile particles will arise from these modified surfaces. Rutile particles have recently been proposed as reinforcement agents of substrates designed for bone tissue engineering applications. In this study, the ability of Ti and rutile particles to modulate secretion of soluble factors involved in bone turnover has been assayed in an in vitro co-culture system of macrophages and human osteoblasts that allows the exchange of soluble factors between both cell types without direct cell contact. Exposure of co-cultured macrophages to sub-cytotoxic doses of Ti or rutile particles did not modify the osteoblastic expression of surface RANKL or the secretion of OPG into the media. Both IL-6 and PGE2 levels increased to a similar extent after treatment with rutile or Ti particles. M-CSF and GM-CSF levels were lower after treatment with rutile particles than with Ti. Experiments employing neutralising antibodies indicate that exposure of co-cultured macrophages to both Ti-based particles induces the release of M-CSF, GM-CSF, IL-6 and PGE2 through up-regulation of IL-1beta and TNF-alpha. We comparatively examined the response of co-cultured macrophages, osteoblasts or both types of cells after exposure to particles. The results indicate that interactions of osteoblasts with particles can modulate the extent of the response initiated by macrophages. Maximal levels of secretions of all tested factors were reached after exposure of co-cultured cells to Ti particles, which is suggestive of the lower bioreactivity of rutile particles.

Determination of metallic traces in kidneys, livers, lungs and spleens of rats with metallic implants after a long implantation time.

Metallic transfer from implants does not stop at surrounding tissues, and metallic elements may be transferred by proteins to become lodged in organs far from the implant. This work presents an in vivo study of metallic implant corrosion to measure metallic element accumulation in organs located far from the implant, such as kidneys, livers, lungs and spleens. The studied metallic implant materials were CoCr alloy, Ti, and the experimental alloy MA956 coated with alpha-alumina. The implants were inserted in the hind legs of Wistar rats. Analysis for Co, Cr, Ti and Al metallic traces was performed after a long exposure time of 12 months by Inductively Coupled Plasma (ICP) with Mass Spectrometry (MS). According to the results, the highest Cr and Ti concentrations were detected in spleens. Co is mainly found in kidneys, since this element is eliminated via urine. Cr and Ti traces increased significantly in rat organs after the long implantation time. The organs of rats implanted with the alpha-alumina coated experimental MA956 did not present any variation in Al content after 12 months, which means there was no degradation of the alumina layer surface.

Rutile and titanium particles differentially affect the production of osteoblastic local factors.

Titanium and its alloys are widely used as implant materials for dental and orthopaedic applications. To improve their wear and corrosion resistance, several surface modifications that give rise to an outer ceramic layer of rutile have been developed. It is expected that after a long period of functional loading, rutile debris will arise from these modified surfaces. We have compared the in vitro biocompatibility of subcytotoxic doses of rutile and titanium particles of phagocytosable size in primary cultures of human osteoblasts. Particles were visualized using a spectral confocal microscope by reflection. Both types of particles aggregated in the culture media and were efficiently internalized by osteoblasts as agglomerates. Treatment of isolated cultures of osteoblasts with rutile particles stimulated the release of IL-6, PGE2, and GM-CSF to a lesser extent than titanium. The influence of macrophages on the particle-induced stimulation of those local factors was analyzed by coculturing TPA-differentiated THP-1 cells with osteoblasts. Under these conditions, levels of IL-6 and PGE2 after treatment of cocultured osteoblasts with rutile particles were lower than after exposure to titanium. These results indicate that rutile debris shows a lower bioreactivity than titanium when tested in cultures of human osteoblasts and support the improved biocompatibility of titanium-based implants modified to create an outer layer of rutile on their surfaces.

Low relapse with oral antibiotics and two-stage exchange for late arthroplasty infections in 40 patients after 2-9 years.

BACKGROUND AND PURPOSE: Exchange surgery in late arthroplasty infection is directed against bacteria adhering to implants. Therapies based on antibiotics that are effective intracellularly have been proposed recently. We have combined both strategies to improve the cure rate. METHODS: 40 consecutive patients (16 hips, 24 knees) were diagnosed with late arthroplasty infection. The organisms isolated were 35 Staphylococcus, 19 of which were methicillin-resistant, 4 Enterococcus, 6 Gram-negative bacilli, and 4 Corynebacterium. The infections were managed by a combined therapy consisting of two-stage exchange surgery and two oral intracellularly-effective antibiotics. The antibiotics were selected according to bacterial sensitivity and intracellular and biofilm effectiveness. Second re-implantation surgery was delayed until clinical and analytical normalization. Patients were in hospital for only 1 week after each surgery, and were followed up prospectively on an outpatient basis (2-9 years). Cure of the infection was defined as absence of clinical, serological, and radiographic signs of infection during the whole follow-up. RESULTS: The infection was resolved in 38/40 patients (15/16 hips and 23/24 knees). INTERPRETATION: Oral antibiotics that are effective intracellularly in combination with two-stage exchange surgery is a promising alternative for treating late arthroplasty infections. Oral antibiotics shorten hospitalization and reduce patient discomfort.

In vitro biocompatibility of an ultrafine grained zirconium.

We have investigated a novel ultrafine grained (UFG) Zr obtained by severe plastic deformation (SPD) which resulted in a refinement of the grain size by several orders of magnitude. Compared to conventional Zr, higher hardness values were measured on UFG Zr. Polished surfaces having similar topographical features from both materials were prepared, as assessed by atomic force microscopy (AFM). Surface hydrophobicity of Zr, evaluated by measuring water contact angles, was unaffected by grain size reduction. In vitro biocompatibility was addressed on conventional and UFG Zr surfaces and, for comparative purposes, a polished Ti6Al4V alloy was also investigated. Cell attachment and spreading, actin and beta-tubulin cytoskeleton reorganisation, fibronectin secretion and cellular distribution as well as cell viability were evaluated by culturing human osteoblastic Saos-2 cells on the surfaces. The osteoblastic response to conventional Zr was found to be essentially identical to Ti6Al4V and was not affected by grain size reduction. In order to evaluate the ability of the surfaces to promote osteogenic maturation and bone matrix mineralisation, human mesenchymal cells from bone marrow were switched to the osteoblastic phenotype by incubation in osteogenic induction media. Compared to undifferentiated mesenchymal cells, alkaline phosphatase activity and formation of mineralisation nodules were enhanced to the same extent on both Zr surfaces and Ti6Al4V alloy after induction of osteoblastic differentiation. In summary, improved mechanical properties together with excellent in vitro biocompatibility make UFG Zr a promising biomaterial for surgical implants.

Differential inflammatory macrophage response to rutile and titanium particles.

Titanium and its alloys are widely used as implant materials for dental and orthopaedic applications due to their advantageous bulk mechanical properties and biocompatibility, compared to other metallic biomaterials. In order to improve their wear and corrosion resistance, several surface modifications that give rise to an outer ceramic layer of rutile have been developed. The ability of rutile wear debris to stimulate the release of inflammatory cytokines from macrophages has not been addressed to date. We have compared the in vitro biocompatibility of sub-cytotoxic doses of rutile and titanium particles in THP-1 cells driven to the monocyte/macrophage differentiation pathway as well as in primary cultures of human macrophages. Confocal microscopy experiments indicated that differentiated THP-1 cells and primary macrophages efficiently internalised rutile and titanium particles. Treatment of THP-1 cells with rutile particles stimulated the release of TNF-alpha, IL-6 and IL-1beta to a lesser extent than titanium. The influence of osteoblasts on the particle-induced stimulation of TNF-alpha and IL-1beta was analysed by co-culturing differentiated THP-1 cells with human primary osteoblasts. Under these conditions, secretion levels of both cytokines after treatment of THP-1 cells with rutile particles were lower than after exposure to titanium. Finally, we observed that primary macrophages released higher amounts of TNF-alpha, IL-6 and IL-1beta after incubation with titanium particles than with rutile. Taken together, these data indicate that rutile particles are less bioreactive than titanium particles and, therefore, a higher biocompatibility of titanium-based implants modified with an outer surface layer of rutile is expected.

Rótula, sustituir o no sustituir / Patellar resurfacing: to be or not to be

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