Interaction between tobramycin and CSA-13 on clinical isolates of Pseudomonas aeruginosa in a model of young and mature biofilms

The bactericidal activity of a cholic acid antimicrobial derivative, CSA-13, was tested against eight strains of Pseudomonas aeruginosa (both reference and clinical strains) and compared with the response to tobramycin. In planktonic cultures, the minimal inhibitory and minimal bactericidal concentrations of CSA-13 and tobramycin were in the 1–25 mg/L range except for one mucoid clinical strain which was much less sensitive to tobramycin (minimal bactericidal concentration, 65–125 mg/L). In young (24 h) biofilms, the sensitivity to CSA-13 was reduced (half-maximal concentration CSA-13 averaged 88 mg/L) and varied among the eight strains. The sensitivity to tobramycin was also very variable among the strains and some were fully resistant to the aminoglycoside. The combination of tobramycin with CSA-13 was synergistic in five strains. Only one strain showed antagonism between the two drugs at low concentrations of CSA-13. One reference and five clinical strains were tested in mature (12 days) biofilms. The effect of CSA-13 was delayed, some strains requiring 9 days exposure to the drug to observe a bactericidal effect. All the strains were tolerant to tobramycin but the addition of CSA-13 with tobramycin was synergistic in three strains. CSA-13 permeabilized the outer membrane of the bacteria (half-maximal concentration, 4.4 mg/L). At concentrations higher than 20 mg/L, it also permeabilized the plasma membrane of human umbilical vein endothelial cells. In conclusion, CSA-13 has bactericidal activity against P. aeruginosa even in mature biofilms and cationic steroid antibiotics can thus be considered as potential candidates for the treatment of chronic pulmonary infections of patients with cystic fibrosis. Considering its interaction with the plasma membrane of eukaryotic cells, less toxic derivatives of CSA-13 should be developed.     

Enhancement of the efficacy of erythromycin in multiple antibiotic-resistant gram-negative bacterial pathogens

Aims:  To improve the efficacy of erythromycin, a hydrophobic antibiotic, against multiple antibiotic-resistant gram-negative bacterial pathogens by enhancing their outer membrane permeability.
Methods and Results:  Fifty-one nonrepeat gram-negative bacterial pathogens of various genera, resistant to multiple antibiotics, including erythromycin, were selected by disc agar diffusion tests. The amphiphilic cationic steroid antibiotic, Ceragenin CSA-13, a potent permeabilizer of bacterial outer membranes, reduced the minimum inhibitory concentration of erythromycin in 92% of the bacterial pathogens selected for the test, when supplemented with erythromycin. A synergistic effect of Ceragenin CSA-13 and erythromycin in combination was also observed. Spectrofluorimetric study confirmed that Ceragenin CSA-13 acts by depolarizing the bacterial outer membrane. The toxicity of Ceragenin CSA-13 was evaluated to be insignificant by measuring 'median lethal dose' (LD₅₀) on mouse model.
Conclusions:  Ceragenin CSA-13 may be useful as an agent to make erythromycin effective against infections caused by multiple antibiotic resistant gram-negative bacteria.
Significance and Impact of the Study:  The outcome of the study suggests erythromycin–Ceragenin combination as a new approach to overcome the problem associated with the rapid emergence of multi-drug-resistant pathogens. The insignificant toxicity of Ceragenin CSA-13, as found, supports the possibility of the application of this compound for human therapeutics.     

In Vitro Bactericidal and Bacteriolytic Activity of Ceragenin CSA-13 against Planktonic Cultures and Biofilms of Streptococcus pneumoniae and Other Pathogenic Streptococci

Ceragenin CSA-13, a cationic steroid, is here reported to show a concentration-dependent bactericidal/bacteriolytic activity against pathogenic streptococci, including multidrug-resistant Streptococcus pneumoniae. The autolysis promoted by CSA-13 in pneumococcal cultures appears to be due to the triggering of the major S. pneumoniae autolysin LytA, an N-acetylmuramoyl-L-alanine amidase. CSA-13 also disintegrated pneumococcal biofilms in a very efficient manner, although at concentrations slightly higher than those required for bactericidal activity on planktonic bacteria. CSA-13 has little hemolytic activity which should allow testing its antibacterial efficacy in animal models.     

Viscoelastic response of human skin to low magnitude physiologically relevant shear

Percutaneous implants are a family of devices that penetrate the skin and all suffer from the same problems of infection because the skin seal around the device is not optimal. Contributing to this problem is the mechanical discontinuity of the skin/device interface leading to stress concentrations and micro-trauma that chronically breaks any seal that forms. In this paper, we have quantified the mechanical behavior of human skin under low-magnitude shear loads over physiological relevant frequencies. Using a stress-controlled rheometer, we have performed isothermal (37 degrees C) frequency response experiments between 0.628 and 75.39rad/s at 0.5% and 0.04% strain on whole skin and dermis-only, respectively. Step-stress experiments of 5 and 10Pa shear loads were also conducted as were strain sweep tests (6.28rad/s). Measurements were made of whole human skin and skin from which the epidermis was removed (dermis-only). At low frequencies (0.628-10rad/s), the moduli are only slightly frequency dependent, with approximate power-law scaling of the moduli, G' approximately G' approximately omega(beta), yielding beta=0.05 for whole skin and beta=0.16 for dermis-only samples. Step-stress experiments revealed three distinct phases. The intermediate phase included elastic "ringing" (damped oscillation) which provided new insights and could be fit to a mathematical model. Both the frequency and step-stress response data suggest that the epidermis provides an elastic rigidity and dermis provides viscoelasticity to the whole skin samples. Hence, whole skin exhibited strain hardening while the dermis-only demonstrated stress softening under step-stress conditions. The data obtained from the low-magnitude shear loads and frequencies that approximate the chronic mechanical environment of a percutaneous implant should aid in the design of a device with an improved skin seal.     

骨科假体表面涂层技术现状

由植入物界面处的相互作用可能引起无菌性松动和假体周围感染。而无菌性松动和假体周围感染仍然是一个难以治疗的问题,并且最终可能导致假体植入失败,引起严重后果。理想的植入物应能促进骨整合,防止细菌粘附,减少细菌感染。骨科植入技术主要基于生物材料的开发和使用,随着材料科学和细胞生物学的发展,已可以用新的植入物表面涂层的进展来解决这些问题。本文回顾总结了时下骨科常见的假体涂层设计和相关问题,以期为进一步研究提供借鉴。     

A nonlinear homogenized finite element analysis of the primary stability of the bone–implant interface

Stability of an implant is defined by its ability to undergo physiological loading–unloading cycles without showing excessive tissue damage and micromotions at the interface. Distinction is usually made between the immediate primary stability and the long-term, secondary stability resulting from the biological healing process. The aim of this research is to numerically investigate the effect of initial implantation press-fit, bone yielding, densification and friction at the interface on the primary stability of a simple bone–implant system subjected to loading–unloading cycles. In order to achieve this goal, human trabecular bone was modeled as a continuous, elasto-plastic tissue with damage and densification, which material constants depend on bone volume fraction and fabric. Implantation press-fit related damage in the bone was simulated by expanding the drilled hole to the outer contour of the implant. The bone–implant interface was then modeled with unilateral contact with friction. The implant was modeled as a rigid body and was subjected to increasing off-axis loading cycles. This modeling approach is able to capture the experimentally observed primary stability in terms of initial stiffness, ultimate force and progression of damage. In addition, it is able to quantify the micromotions around the implant relevant for bone healing and osseointegration. In conclusion, the computationally efficient modeling approach used in this study provides a realistic structural response of the bone–implant interface and represents a powerful tool to explore implant design, implantation press-fit and the resulting risk of implant failure under physiological loading.     

Failure mechanism of the all-polyethylene glenoid implant

Fixation failure of glenoid components is the main cause of unsuccessful total shoulder arthroplasties. The characteristics of these failures are still not well understood, hence, attempts at improving the implant fixation are somewhat blind and the failure rate remains high. This lack of understanding is largely due to the fundamental problem that direct observations of failure are impossible as the fixation is inherently embedded within the bone.Twenty custom made implants, reflecting various common fixation designs, and a specimen set-up was prepared to enable direct observation of failure when the specimens were exposed to cyclic superior loads during laboratory experiments. Finite element analyses of the laboratory tests were also carried out to explain the observed failure scenarios.All implants, irrespective of the particular fixation design, failed at the implant–cement interface and failure initiated at the inferior part of the component fixation. Finite element analyses indicated that this failure scenario was caused by a weak and brittle implant–cement interface and tensile stresses in the inferior region possibly worsened by a stress raiser effect at the inferior rim.The results of this study indicate that glenoid failure can be delayed or prevented by improving the implant/cement interface strength. Also any design features that reduce the geometrical stress raiser and the inferior tensile stresses in general should delay implant loosening.     

Synthesis and biological evaluation of (3,4,5-trimethoxyphenyl)indol-3-ylmethane derivatives as potential antivascular agents

Combretastatin A-4 (CSA-4), a stilbene derivative, is a potent vascular disrupting agent (VDA) with the structural requirement of a cis-configuration to maintain a molecular geometry and a correct orientation of both phenyl groups. A series of indolic analogues of CSA-4 was synthesized by means of an efficient strategy. Six compounds (20b, 25b-27b, 32b, and 35b) were identified as potent inhibitors of tubulin polymerization and also displayed cytotoxic activities on B16 melanoma cells at a nanomolar level. Both activities were well correlated with the ability to induce morphological changes of EA.hy 926 endothelial cells. In conclusion, the cis-stilbene skeleton of CSA-4 could conveniently be replaced by the 3-aroylindolic moiety, thus avoiding any isomerization leading to inactive trans compounds.     

Mycobacterium abscessus infection of a Norplant contraceptive implant site.

The authors report a case of Mycobacterium abscessus infection of a subdermal levonogestrel implant (Norplant) site. The infection lasted 12 weeks and was indolent, skin manifestations were low grade and difficult to detect. Culture of exudate samples showed that M. abscessus was the only causative agent. After the implant was removed the patient''s arm healed uneventfully without antimycobacterial therapy. The authors recommend that if Gram staining of apparently infected material from an implant site does not reveal a causative organism, then cultures should be done for mycobacteria and fungi. Kinyoun staining for acid-fast bacteria and calcoflour-white staining for fungi should also be performed. The implant should be removed and the patient given antimicrobial therapy as indicated. The authors emphasize the need to be aware of the potential for M. abscessus infection of implant sites and stress that appropriate microbiologic culture procedures are essential for accurate diagnosis.     

Computational simulation of dental implant osseointegration through resonance frequency analysis

The aim of this study is to predict the evolution of the resonance frequency of the bone-implant interface in a dental implant by means of finite element simulation. A phenomenological interface model able to simulate the mechanical effects of the osseointegration process at the bone-implant interface is applied and compared with some experimental results in rabbits. An early stage of slow bone ingrowth, followed by a faster osseointegration phase until final stability is predicted by the simulations. The evolution of the resonance frequency of the implant and surrounding tissues along the simulation period was also obtained, observing a 3-fold increase in the first principal frequency. These findings are in quantitative agreement with the experimental measurements and suggest that the model can be useful to evaluate the influence of mechanical factors such as implant geometry or implant loading on the indirect evaluation of the process of implant osseintegration.     

Surface porous fibre-reinforced composite bulk bone substitute

The aim of this study was to describe and evaluate the significance of a porous surface with bioactive glass granules (S53P4) covering an artificial bulk material based on polymethylmetacrylate (PMMA) and fibre-reinforced composite (FRC) technology. Effort was focused particularly on characters of the porous surface and biomechanical properties of the material in vitro, and test in vivo the implant in reconstruction in an experimental long bone segment defect model. The defect, 10 mm in length, created in the shaft of rabbit tibia, was reconstructed by the implant and fixed by intramedullary K-wires. The implant was incorporated within 4 weeks by new bone growth from the host bone covering particularly its posterior surface and cortex/implant junctions with bridging trabecular bone. Later, at 8 weeks, new bone was found also at the cortex/implant interface and in the medullary canal of the implant. Histometric measurements revealed direct bone/implant surface contact in 34% at the interface. Bioactive glass granules in the porous surface evoked the most direct contact with bone. The implants manufactured from PMMA only served as a control group, and showed significantly lower osteoconductive properties. Biomechanical measurements in vitro of fibre-reinforced PMMA specimens revealed values for bending strength and the flexural modulus to match them to human bone. This artificial bulk bone material based on PMMA/FRC technology seems to have proposing properties to be used as a bone substitute on load-bearing conditions. This revised version was published online in July 2006 with corrections to the Cover Date.     

Breast reconstruction using tissue expanders and implants in Hodgkin's patients with prior mantle irradiation.

Women treated for Hodgkin's disease with mantle irradiation have an increased risk for developing breast cancer. Typically, breast malignancy in Hodgkin's patients presents bilaterally in a younger age group. Skin flap ischemia, poor skin expansion, implant extrusion, capsular contracture, and poor cosmesis are common sequelae of tissue expander/implant breast reconstruction after breast irradiation for failed breast conservation therapy. This has led most surgeons to favor autologous tissue reconstruction in this setting. This study was performed to determine the efficacy of tissue expander/implant breast reconstruction in breast cancer patients who have been treated with prior mantle irradiation for Hodgkin's disease. A retrospective analysis of all breast cancer patients with a history of Hodgkin's disease and mantle irradiation treated with mastectomy and tissue expander/implant reconstruction between 1992 and 1999 was performed. There were seven patients, with a mean age of 35 years (range, 28 to 42 years). The average interval between mantle irradiation and breast cancer diagnosis was 16 years (range, 12 to 23 years). All patients underwent two-stage reconstruction. Textured surface tissue expanders were placed in a complete submuscular position at the time of mastectomy. Expansion was initiated 2 weeks after insertion and continued on a weekly basis until completion. Expanders were replaced with textured surface saline-filled implants as a second stage. Patients were evaluated for skin flap ischemia, infection, quality of skin expansion, implant extrusion, capsular contracture, rippling, symmetry, and final aesthetic outcome. Breast cancer was bilateral in five patients and unilateral in two. Two patients did not undergo simultaneous bilateral breast reconstruction because of metachronous cancer development. One of the patients had an initial transverse rectus abdominis muscle flap breast reconstruction, followed by a tissue expander/implant reconstruction of the opposite breast. The average follow-up was 3 years. Complications were limited to one case of cellulitis after implant placement that resolved with intravenous antibiotics. There were no cases of skin flap ischemia, poor skin expansion, or implant extrusion. Overall patient satisfaction was high and revisions were not requested or required. Symmetry was best achieved with bilateral implants. This study demonstrates the efficacy of tissue expander/implant breast reconstruction in patients treated with prior mantle irradiation. In this series, tissue expansion was reliable with low morbidity. Second-stage placement of permanent implants yielded good aesthetic results without significant capsular contracture. Mantle irradiation did not appear to compromise the prosthetic breast reconstruction. Tissue expander/implant breast reconstruction should remain a viable option in this category of irradiated patients.     

Long-term use of polyurethane breast prostheses: a 14-year experience

I have used polyurethane prostheses for the past 14 years, implanting 220 implants into 130 patients who desired breast reconstruction after subcutaneous mastectomy or cancer ablation or simply breast augmentation. I theorize that a polyurethane-covered implant resists contracture, retaining its compressibility because the fibroblasts proliferate into the polyurethane in many different directions. When the fibrils contract, the forces of contracture counterbalance one another, resisting contracture. However, when smooth prostheses are implanted, fibrils are directed in a circular fashion around the implant and naturally contract, leading to firmer breasts. There were 115 prostheses inserted following subcutaneous mastectomy, and 22 percent developed contracted capsules. Seven implants became exposed because of skin necroses; one was removed because of a Staphylococcus infection; and two patients developed a combination of polyurethane and silicone granulomas. These developed only with the earlier implant, where there was shedding of the polyurethane sponge layer and silicone bled from the low-viscosity silicone used in the earlier implants. No granulomas were noted with the currently used Surgitek Replicon implant. Eighty-five breasts were reconstructed after cancer ablation with polyurethane implants, and the contracture rate was 2.3 percent. Other complications were minimal. A smaller group of patients had augmentation mammaplasty, and 20 prostheses were placed in 10 patients. A 15 percent contracture rate was noted in this group. In this study, 82 percent of patients were followed for up to 14 years. Capsular contractures occurred in 30 implants between 1 and 11 years, for an average recurrence at 6.3 years. The overall contracture rate was 13 percent. Other complications were minimal. All implants were placed subcutaneously or subglandularly, and all were drained.     

Immunohistochemical characteristics of chicken spleen ellipsoids using newly established monoclonal antibodies

Ellipsoids, the extra-vasculature sites surrounding penicilliary capillaries of the chicken spleen, play critical roles in the immune response and also in the clearance of pathogens or other particles. The meshwork of ellipsoids is formed by fibroblastic reticular cells. To characterize ellipsoidal reticular cells, a series of monoclonal antibodies against the chicken spleen have been developed. Of these antibodies, CSA-1 antibody reacts with fibroblastic reticular cells in ellipsoids and with endothelial cells. The reticular nature of positive cells in ellipsoids is indicated by immuno-electron microscopy, and by double-staining with anti-heat-shock protein 47 kDa (hsp47) antibody. The reaction of CSA-1 with reticular cells is limited in ellipsoids; CSA-1 does not react with reticular cells in other lymphoid organs. These findings indicate that ellipsoidal reticular cells share the antigen with endothelial cells. Ontogenic studies reveal that, on embryonic day 18, the development of ellipsoids is completed, penicilliary capillaries become fenestrated, and CSA-1 expression in ellipsoids begins. These findings suggest that CSA-1 is expressed on the cell surface of ellipsoidal reticular cells once they are exposed to blood flow.     

Efficient computational method for assessing the effects of implant positioning in cementless total hip replacements

The present work describes a statistical investigation into the effects of implant positioning on the initial stability of a cementless total hip replacement (THR). Mesh morphing was combined with design of computer experiments to automatically construct Finite Element (FE) meshes for a range of pre-defined femur-implant configurations and to predict implant micromotions under joint contact and muscle loading. Computed micromotions, in turn, are postprocessed using a Bayesian approach to: (a) compute the main effects of implant orientation angles, (b) predict the sensitivities of the considered implant performance metrics with respect to implant ante-retroversion, varus-valgus and antero-posterior orientation angles and (c) identify implant positions that maximise and minimise each metric. It is found that the percentage of implant area with micromotion greater than 50 μm, average and maximum micromotions are all more sensitive to antero-posterior orientation than ante-retroversion and varus-valgus orientation. Sensitivities, combined with the main effect results, suggest that bone is less likely to grow if the implant is increasingly moved from the neutral position towards the anterior part of the femur, where the highest micromotions occur. The computed implant best position leads to a percentage of implant area with micromotion greater than 50 μm of 1.14 when using this metric compared to 14.6 and 5.95 in the worst and neutrally positioned implant cases. In contrast, when the implant average/maximum micromotion is used to assess the THR performance, the implant best position corresponds to average/maximum micromotion of 9 μm/59 μm, compared to 20 μm/114 μm and 13 μm/71 μm in the worst and neutral positions, respectively. The proposed computational framework can be extended further to study the effects of uncertainty and variability in anatomy, bone mechanical properties, loading or bone-implant interface contact conditions.     

A Polymethyl Methacrylate Method for Large Specimens of Mineralized Bone with Implants

A simple modified polymethyl methacrylate method is described for large mineralized bone specimens with implants and bioactive materials which produces consistently good histological preservation of the interface between bone and implant. Human femoral heads, whole rabbit condyles and canine tibias and femurs containing implants consisting of hydroxyapatite, smooth polyethylene, porous polyethylene and carbon were dehydrated in ascending grades of ethanol and cleared with xylene on an automated tissue processor which alternated vacuum and pressure for 22 hr. Infiltration was done with washed polymethyl methacrylate at 4 C under vacuum for 13 days. Polymerization was carried out in wide-mouth glass jars at 38 C for 36 hr so that the total processing time was less than 20 days. The only important modification was in the polymethyl methacrylate, which had less plasticizer than usual in order to give a harder block. This enabled production of 4 μm sections with good preservation of mineralized and cellular areas for the study of metabolic bone diseases, morphometry, fluorochrome labelling and interface analysis with the implant in situ.     

Experimental evidence of impingement induced strains at the interface and the periphery of an embedded acetabular cup implant

After total hip arthroplasty, impingement of implant components may occur during every-day patient activities causing increased shear stresses at the acetabular implant-bone interface. In the literature, impingement related lever-out moments were noted for a number of acetabular components. But there is little information about pelvic load transfer. The aim of the current study was to measure the three-dimensional strain distribution at the macrostructured hemispherical interface and in the periphery of a standard acetabular press-fit cup in an experimental implant-bone substitute model. An experimental setup was developed to simulate impingement loading via a lever arm representing the femoral component and the lower limb. In one experimental setup 12 strain gauges were embedded at predefined positions in the periphery of the acetabular cup implant inside a tray, using polyurethane composite resin as a bone substitute material. By incremental rotation of the implant tray in steps of 10 and 30 deg, respectively, the strains were measured at evenly distributed positions. With the described method 288 genuine strain values were measured in the periphery of an embedded acetabular cup implant in one experimental setup. In two additional setups the strains were evaluated at different distances from the implant interface. Both in radial and meridional interface directions strain magnitudes reach their peak near the rim of the cup below the impingement site. Values of equatorial strains vary near zero and reach their peaks near the rim of the cup on either side and in some distance from the impingement site. Interestingly, the maximum of averaged radial strains does not occur, as expected, close to the interface but at an interface offset of 5.6 mm. With the described experimental setup it is now possible to measure and display the three-dimensional strain distribution in the interface and the periphery of an embedded acetabular cup implant. The current study provides the first experimental proof of the high local stresses gradients in the direct vicinity of the impingement site. The results of the current study help for a better understanding of the impingement mechanism and its impact on acetabular cup stability.     

Morphological and numerical studies of the stress compatibility of patella implants]

Failure of total knee arthroplasty is relatively often caused by problems of the patellofemoral replacement. The purpose of this study was to analyze the distribution of stresses within an anatomical patella and the changes in stress distribution after patellar resurfacing with a Miller-Galante I patellar implant using two- and three dimensional finite element models (FEM). To assess validity, FEM results were compared with morphological findings from contact radiographs and densitographs. Internal orientation of bone trabeculae is in good agreement with the orientation of theoretically calculated principal stresses. Almost unchanged principal tensile stresses after implantation, together with the lack of extreme stress peaks within the cancellous bone ensure stress compatibility of the implant. In the case of a firmly seated implant with good bone ingrowth, increased von Mises stresses are found near the fixation peg/plate junction. Their relevance for improved bone ingrowth near this part of the interface is emphasized. At the same time, material failure at the peg/plate junction can be better understood. An analysis of the early postoperative period assuming nonlinear interface conditions failed to demonstrate an uniform distribution of normal and tangential interface forces.     

Simulation of impact test for determining "health" of percutaneous bone anchored implants

There is an ongoing requirement for a clinically relevant, noninvasive technique to monitor the integrity of percutaneous implants used for dental restorations, bone-anchored hearing aids, and to retain extra-oral prostheses (ear, eye, nose, etc). Because of the limitations of conventional diagnostic techniques (CT, MRI), mechanical techniques that measure the dynamic response of the implant-abutment system are being developed. This paper documents a finite element analysis that simulates a transient response to mechanical impact testing using contact elements. The detailed model allows for a specific interface between the implant and bone and characterizes potential clinical situations including loss of bone margin height, loss of osseointegration, and development of a soft connective tissue layer at the bone-implant interface. The results also show that the expected difference in interface stiffness between soft connective tissue and osseointegrated bone will cause easily measurable changes in the response of the implant/abutment system. With respect to the loss of bone margin height, changes in the order of 0.2 mm should be detectable, suggesting that this technique is at least as sensitive as radiography. A partial loss of osseointegration, while not being as readily evident as a bone margin loss, would still be detectable for losses as small as 0.5 mm.     

Influence of the stiffness of bone defect implants on the mechanical conditions at the interface--a finite element analysis with contact

The study focused on the influence of the implant material stiffness on stress distribution and micromotion at the interface of bone defect implants. We hypothesized that a low-stiffness implant with a modulus closer to that of the surrounding trabecular bone would yield a more homogeneous stress distribution and less micromotion at the interface with the bony bed. To prove this hypothesis we generated a three-dimensional, non-linear, anisotropic finite element (FE) model. The FE model corresponded to a previously developed animal model in sheep. A prismatic implant filled a standardized defect in the load-bearing area of the trabecular bone beneath the tibial plateau. The interface was described by face-to-face contact elements, which allow press fits, friction, sliding, and gapping. We assumed a physiological load condition and calculated contact pressures, shear stresses, and shear movements at the interface for two implants of different stiffness (titanium: E=110GPa; composite: E=2.2GPa). The FE model showed that the stress distribution was more homogeneous for the low-stiffness implant. The maximum pressure for the composite implant (2.1 MPa) was lower than for the titanium implant (5.6 MPa). Contrary to our hypothesis, we found more micromotion for the composite (up to 6 microm) than for the titanium implant (up to 4.5 microm). However, for both implants peak stresses and micromotion were in a range that predicts adequate conditions for the osseointegration. This was confirmed by the histological results from the animal studies.