The use of implant biomaterials for prosthetic reconstructive surgery and osteosynthesis is consolidated in the orthopaedic field, improving the quality of life of patients and allowing for healthy and better ageing. However, there is the lack of advanced innovative methods to investigate the potentialities of smart biomaterials, particularly for the study of local effects of implant and osteointegration. Despite the complex process of osseointegration is difficult to recreate in vitro, the growing challenges in developing alternative models require to set-up and validate new approaches. Aim of the present study is to evaluate an advanced in vitro tissue culture model of osteointegration of titanium implants in human trabecular bone. Cubic samples (1.5×1.5 cm) of trabecular bone were harvested as waste material from hip arthroplasty surgery (CE AVEC 829/2019/Sper/IOR); cylindrical defects (2 mm Ø, 6 mm length) were created, and tissue specimens assigned to the following groups: 1) empty defects- CTR-; 2) defects implanted with a cytotoxic copper pin (Merck cod. 326429)- CTR+; 3) defects implanted with standard titanium pins of 6 µm-rough (ZARE S.r.l) -Ti6. Tissue specimens were cultured in mini rotating bioreactors in standard conditions, weekly assessing viability. At the 8-week-timepoint, immunoenzymatic, microtomographic, histological and histomorphometric analyses were performed. The model was able to simulate the effects of implantation of the materials, showing a drop in viability in CTR+, differently from Ti6 which appears to have a trophic effect on the bone. MicroCT and histological analysis supported the results, with lower BV/TV and Tb.Th values observed in CTR- compared to CTR+ and Ti6 and signs of matrix and bone deposition at the implant site. The collected data suggest the reliability of the tested model which can recreate the osseointegration process in vitro and can therefore be used for preliminary evaluations to reduce and refine in vivo preclinical models. Acknowledgment: This work was supported by Emilia-Romagna Region for the project “Sviluppo di modelli biologici in vitro ed in silico per la valutazione e predizione dell'osteointegrazione di dispositivi medici da impianto nel tessuto osseo”

We studied the effects of coating titanium implants with teicoplanin and clindamycin in 30 New Zealand White rabbits which were randomly assigned to three groups. The intramedullary canal of the left tibia of each rabbit was inoculated with 500 colony forming units of Staphylococcus aureus. Teicoplanin-coated implants were implanted into rabbits in group 1, clindamycin-coated implants into rabbits in group 2, and uncoated implants into those in group 3. All the rabbits were killed one week later. The implants were removed and cultured together with pieces of tibial bone and wound swabs. The rate of colonisation of the organisms in the three groups was compared. Organisms were cultured from no rabbits in group 1, one in group 2 but from all in group 3. There was no significant difference between groups 1 and 2 (p = 1.000). There were significant differences between groups 1 and 3 and groups 2 and 3 (p < 0.001). Significant protection against bacterial colonisation and infection was found with teicoplanin- and clindamycin-coated implants in this experimental model

We have studied the effect of hydroxyapatite (HA) coating in 15 ovariectomised and 15 normal rats which had had a sham procedure. Twenty-four weeks after operation, HA-coated implants were inserted into the intramedullary canal of the right femur and uncoated implants into the left femur. The prostheses were removed four weeks after implantation. Twelve specimens in each group had mechanical push-out tests. Sagittal sections of the other three were evaluated by SEM.

The bone mineral density (BMD) of the dissected left tibia was measured by dual-energy x-ray absorptiometry. The difference in BMD between the control and ovariectomised tibiae was 35.01 mg/cm² (95% CI, 26.60 to 43.42). The push-out strength of the HA-coated implants was higher than that of the uncoated implants in both groups (p < 0.0001), but the HA-coated implants of the ovariectomised group had a reduction in push-out strength of 40.3% compared with the control group (p < 0.0001).

Our findings suggest that HA-coated implants may improve the fixation of a cementless total hip prosthesis but that the presence of osteoporosis may limit the magnitude of this benefit.

Decreasing the bulk weight without losing the biomechanical properties of commercial pure titanium (Cp-Ti) medical implants is now possible by using Laser Powder Bed Fusion (L-PBF) technology. Gyroid lattice structures that have precious mechanical and biological advantages because of similarity to trabecular bone. The aim of the study was to design and develop L-PBF process parameter optimization for manufacturing gyroid lattice Cp-Ti structures. The cleaning process was then optimized to remove the non-melted powder from the gyroid surface without mechanical loss.

Gyroid cubic designs were created with various relative densities by nTopology. L-PBF process parameter optimization was progressed using with Cp-Ti (EOS TiCP Grade2) powder in the EOS M290 machine to achieve parts that have almost full dense and dimensional accuracy. The metallography method was made for density. Dimensional accuracy at gyroid wall thicknesses was investigated between designed and manufactured via stereomicroscope, also mechanical tests were applied with real time experiment and numerical analysis (ANSYS). Mass loss and strut thickness loss were investigated for chemical etching cleaning process.

Gyroid parts had 99,5% density. High dimensional accuracy was achieved during L-PBF process parameters optimization. Final L-PBF parameters gave the highest 19% elongation and 427 MPa yield strength values at tensile test. Mechanical properties of gyroid were controlled with changing relative density. A minute chemical etching provided to remove non-melted powders.

Compression test results of gyroids at numerical and real-time analysis gave unrelated while deformation behaviors were compatible with each other. Gyroid Cp-Ti osteosynthesis mini plates will be produced with final L-PBF process parameters. MTT cytotoxicity test will be characterized for cell viability.

Acknowledgements This project is granted by TUBITAK (120N943). Feza Korkusuz MD is a member of the Turkish Academy of Sciences (TÜBA).

Extensor mechanism and abductor reconstructions in total joint arthroplasty are problematic. Growing tendon into a metallic implant would have great reconstructive advantages. With the introduction of porous metal implants, it was hoped that tendons could be directly attached to implants. However, the effects of the porous metal structure on tissue growth and pore penetration is unknown. In this rat model, we investigated the effect of pore size on tendon repair fixation using printed titanium implants with differing pore sizes. There were four groups of six Sprague Dawley rats (n = 28) plus control (n=4). Implants had pore sizes of 400µm (n=8), 700µm (n=8), and 1000µm (n=8). An Achilles tendon defect was created, and the implant positioned and sutured between the cut ends. Harvest occurred at 12-weeks. Half the specimens underwent tensile load to failure testing, the other half fixed and processed for hard tissue analysis. Average load to failure was 72.6N for controls (SD 10.04), 29.95N for 400µm (SD 17.95), 55.08N for 700µm (SD 13.47), and 63.08N for 1000µm (SD 1.87). The load to failure was generally better in the larger pore sizes. Histological evaluation showed that there was fibrous tendon tissue within and around the implant material, with collagen fibers organized in bundles. This increases as the pore diameter increases. Printing titanium implants allows for precise determination of pore size and structure. Our results showed that tendon repair utilizing implants with 700µm and 1000µm pores exhibited similar load to failure as controls. Using a defined pore structure at the attachment points of tendons to implants may allow predictable tendon to implant reconstruction at the time of revision arthroplasty

Production of porous titanium bone implants is a highly promising research and application area due to providing high osseointegration and achieving the desired mechanical properties. Production of controlled porosity in titanium implants is possible with laser powder bed fusion (L- PBF) technology. The main topics of this presentation includes the L-PBF process parameter optimization to manufacture thin walls of porous titanium structures with almost full density and good mechanical properties as well as good dimensional accuracy. Moreover, the cleaning and coating process of these structures to further increase osseointegration and then in-vitro biocompatibility will be covered

Infection of implanted medical devices (biomaterials), like titanium orthopaedic implants, can have disastrous consequences, including removal of the device. These so-called biomaterial-associated infections (BAI) are mainly caused by Staphylococcus aureus and Staphylococcus epidermidis. To prevent biofilm formation using a non-antibiotic based strategy, we aimed to develop a novel permanently fixed antimicrobial coating for titanium devices based on stable immobilized quaternary ammonium compounds (QACs). Medical grade titanium implants were dip-coated in subsequent solutions of hyperbranched polymer, polyethyleneimine and 10 mM sodium iodide, and ethanol. The QAC-coating was characterized using water contact angle measurements, scanning electron microscopy, FTIR, AFM and XPS. The antimicrobial activity of the coating was evaluated against S. aureus strain JAR060131 and S. epidermidis strain ATCC 12228 using the JIS Z 2801:2000 surface microbicidal assay. Lastly, we assessed the in vivo antimicrobial activity in a mouse subcutaneous implant infection model with S. aureus administered locally on the QAC-coated implants prior to implantation to mimic contamination during surgery. Detailed material characterization of the titanium samples showed the presence of a homogenous and stable coating layer at the titanium surface. Moreover, the coating successfully killed S. aureus and S. epidermidis in vitro. The QAC-coating strongly reduced S. aureus colonization of the implant surface as well as of the surrounding tissue, with no apparent macroscopic signs of toxicity or inflammation in the peri-implant tissue at 1 and 4 days after implantation. An antimicrobial coating with stable quaternary ammonium compounds on titanium has been developed which holds promise to prevent BAI. Non-antibiotic-based antimicrobial coatings have great significance in guiding the design of novel antimicrobial coatings in the present, post-antibiotic era. Acknowledgements: This research was financially supported by the Health∼Holland/LSH-TKI call 2021–2022, project 25687, NACQAC: ‘Novel antimicrobial coatings with stable non-antibiotic Quaternary Ammonium Compounds and photosensitizer technology'

Aims. This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation. Methods. In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload. Results. Utilizing an OVX rat model, we observed significant alterations in bone mass and osseointegration due to VIT administration in aged rats with iron overload. The observed effects were concomitant with reductions in bone metabolism, oxidative stress, and inflammation. To elucidate whether these effects are associated with osteoclast and osteoblast activity, we conducted in vitro experiments using MC3T3-E1 cells and RAW264.7 cells. Our findings indicate that iron accumulation suppressed the activity of MC3T3-E1 while enhancing RAW264.7 function. Furthermore, iron overload significantly decreased oxidative stress levels; however, these detrimental effects can be mitigated by VIT treatment. Conclusion. Collectively, our data provide compelling evidence that VIT has the potential to reverse the deleterious consequences of iron overload on osseointegration and bone mass during ageing. Cite this article: Bone Joint Res 2024;13(9):427–440

The success of cementless orthopaedic implants relies on bony ingrowth and active bone remodelling. Much research effort is invested to develop implants with controllable surface roughness and internal porous architectures that encourage these biological processes. Evaluation of these implants requires long-term and costly animal studies, which do not always yield the desired outcome requiring iteration. The aim of our study is to develop a cost-effective method to prescreen design parameters prior to animal trials to streamline implant development and reduce live animal testing burden. Ex vivo porcine cancellous bone cylinders (n=6, Ø20×12mm) were extracted from porcine knee joints with a computer-numerically-controlled milling machine under sterile conditions within 4 hours of animal sacrifice. The bone discs were implanted with Ø6×12mm additive manufactured porous titanium implants and were then cultured for 21days. Half underwent static culture in medium (DMEM, 10% FBS, 1% antibiotics) at 37°C and 5% CO. 2. The rest were cultured in novel high-throughput stacked configuration in a bioreactor that simulated physiological conditions after surgery: the fluid flow and cyclic compression force were set at 10ml/min and 10–150 N (1Hz,5000 cycles/day) respectively. Stains were administered at days 7 and 14. Samples were evaluated with widefield microscopy, scanning electron microscopy (SEM) and with histology. More bone remodelling was observed on the samples cultured within the bioreactor: widefield imaging showed more remodelling at the boundaries between the implant-bone interface, while SEM revealed immature bone tissue integration within the pores of the implant. Histological analysis confirmed these results, with many more trabecular struts with new osteoid formation on the samples cultured dynamically compared to static ones. Ex vivo bone can be used to analyse new implant technologies with lower cost and ethical impact than animal trial. Physiological conditions (load and fluid flow) promoted bone ingrowth and remodelling

Preventing infections in joint replacements is a major ongoing challenge, with limited effective clinical technologies currently available for uncemented knee and hip prostheses. This research aims to develop a coating for titanium implants, consisting of a supported lipid bilayer (SLB) encapsulating an antimicrobial agent. The SLB will be robustly tethered to the titanium using self-assembled monolayers (SAMs) of octadecylphosphonic acid (ODPA). The chosen antimicrobial is Novobiocin, a coumarin-derived antibiotic known to be effective against resistant strains of Staphylococcus aureus. ODPA SAMs were deposited on TiO. 2. -coated quartz crystal microbalance (QCM) sensors using two environmentally friendly non-polar solvents (anisole and cyclopentyl methyl ether, CPME), two concentrations of ODPA (0.5mM and 1mM) and two processing temperatures (21°C and 60°C). QCM, water contact angle measurements, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and temperature-programmed desorption mass spectrometry (TPD-MS) were used to characterise the ODPA SAM. A SLB with encapsulated Novobiocin was subsequently developed on the surface of the ODPA SAM using fluorescent lipids and a solvent assisted method. The prototype implant surface was tested for antimicrobial activity against S. aureus. A well-ordered, uniform ODPA SAM was rapidly formed using 0.5 mM ODPA in CPME at 21°C during 10 min, as confirmed by high Sauerbrey mass (≍285-290 ng/cm. 2. ), high atomic percentage phosphorus (detected using XPS) and high water contact angles (117.6±2.5°). QCM measurements combined with fluorescence microscopy provided evidence of complete planar lipid bilayer formation on the titanium surface using a solvent assisted method. Incorporation of Novobiocin into the SLB resulted in reduced attachment and viability of S. aureus. Key parameters were established for the rapid, robust and uniform formation of an ODPA SAM on titanium (solvent, temperature and concentration). This allowed the successful formation of an antimicrobial SLB, which demonstrated potential for reducing attachment and viability of pathogens associated with joint replacement infections

In orthopedic surgery, implant infections are a serious issue and difficult to treat. The aim of this study was to use superparamagnetic nanoporous silica nanoparticles (MNPSNP) as candidates for directed drug delivery. Currently, short blood circulation half-life due to interactions with the host's immune system hinder nanoparticles in general from being clinically used. PEGylation is an approach to reduce these interactions and to enhance blood circulation time. The effect of PEGylation of the used . 68. Ga-labelled MNPSNP on the distribution and implant accumulation was examined by PET/CT imaging and gamma counting in an implant mouse model. Female Balb/c mice (n=24) received a magnetic implant subcutaneously on the left and a titanium implant on the right hind leg. On day one, 12 of these mice received an additional clodronate®-injection for macrophage depletion. On the second postoperative day, mice were anaesthetized and MNPSNP (native or PEGylated) injected intravenously, followed by a dynamic PET-scan over 60 minutes, a CT- and a static PET-scan at 120 min. As control, 12 mice received only . 68. Ga-MNPSNP (native or PEGylated). Gamma counting of inner organs, urine, blood and implant area was performed as further final analysis. Although PEGylation of the nanoparticles already resulted in lower liver uptakes, both variants of . 68. Ga-labeled MNPSNP accumulated in liver and spleen. Combination of PEGylation with clodronate®-injection led to a highly significant effect whereas clodronate®-injection alone could not reveal significant differences. In gamma counting, a significantly higher %I.D./g was found for the tissue surrounding the magnetic implants compared to the titanium control, although in a low range. PEGylation and/or clodronate®-injection revealed no significant differences regarding nanoparticle accumulation at the implantation site. PEGylation increases circulation time, but MNPSNP accumulation at the implant site was still insufficient for treatment of infections. Additional efforts have to further increase circulation time and local accumulation. Acknowledgements: This work is funded by the German Research Foundation (DFG, project number 280642759)

Abstract. Objectives. Unicompartmental and total knee arthroplasty (UKA and TKA) are successful treatments for osteoarthritis, but monolithic implants disrupt the natural homeostasis of bone which leads to bone loss over time. This can cause problems if the implant needs to be revised. This study aimed to demonstrate that tibial implants made from titanium lattice could replace the tibial condyle surface while minimising disruption of the bone's natural mechanical loading environment. A secondary aim was to determine whether implants perform better if they replicate more closely bone's mechanical modulus, anisotropy and spatial heterogeneity. This study was conducted in a human cadaveric model. Methods. In a cadaveric model, UKA and TKA procedures were performed on 8 fresh-frozen knee specimens by a board-certified consultant orthopaedic surgeon, using tibial implants made from conventional monolithic material and titanium lattice structures. Stress at the bone-implant interfaces was measured with pressure film and compared to the native knee. Results. Titanium lattice implants were able to restore the mechanical environment seen in the native tibia for both UKA and TKA designs. Maximum stress at the bone-implant interface ranged from 1.2–3.3MPa compared to 1.3–2.7MPa for the native tibia. The conventional UKA and TKA implants reduced the maximum stress in the bone by a factor of 10 and 9.7 respectively. The conventional UKA and TKA implants caused 71% and 77% of bone surface area to be underloaded compared to the native tibia. Conclusions. Titanium lattice implants can maintain the natural mechanical loading in the proximal tibia after UKA and TKA. This may help maintain normal bone homeostasis throughout the life of the implant. These encouraging data indicate normal bone homeostasis can be maintained after arthroplasty using manufacturing methods already in widespread use. This would maintain bone quality throughout the life of the implant and alleviate complications at revision surgery

Miniscrew implants (MSIs) are widely used to provide absolute anchorage for the orthodontic treatment. However, the application of MSIs is limited by the relatively high failure rate (22.86%). In this study, we wished to investigate the effects of amorphous and crystalline biomimetic calcium phosphate coating on the surfaces of MSIs with or without the incorporated BSA for the osteointegration process with an aim to facilitate the early loading of MSIs. Amorphous and crystalline coatings were prepared on titanium mini-pin implants. Characterizations of coatings were examined by Scanning electron microscopy (SEM), Confocal laser-scanning dual-channel-fluorescence microscopy (CLSM) and Fourier-transform infrared spectroscopy (FTIR). The loading and release kinetics of bovine serum albumin (BSA) were evaluated by Enzyme linked immunosorbent assay (ELISA). Activity of alkaline phosphate (ALP) was measured by using the primary osteoblasts. In vivo, a model of metaphyseal tibial implantation in rats was used (n=6 rats per group). We had 6 different groups: no coating no BSA, no coating but with surface adsorption of BSA and incorporation of BSA in the biomimetic coating in the amorphous and crystalline coatings. Time points were 3 days, 1, 2 and 4 weeks. Histological and histomorphometric analysis were performed and the bone to implant contact (BIC) of each group was compared. In vitro, the incorporation of BSA changed the crystalline coating from sharp plates into curly plates, and the crystalline coating showed slow-release profile. The incorporation of BSA in crystalline coating significantly decreased the activity of ALP in vitro. In vivo study, the earliest significant increase of BIC appeared in crystalline coating group at one week. The crystalline coating can serve as a carrier and slow release system for the bioactive agent and accelerate osteoconductivity at early stage in vivo. The presence of BSA is not favorable for the early establishment of osteointegration

Orbital floor (OF) fractures are commonly treated by implanting either bioinert titanium or polyethylene implants, or by autologous grafts. A personalized implant made of biodegradable and osteopromotive poly(trimethylene carbonate) loaded with hydroxyapatite (PTMC-HA) could be a suitable alternative for patients where a permanent implant could be detrimental. A workflow was developed from the implant production using stereolithography (SLA) based on patient CT scan to the implantation and assessment its performance (i.e. implant stability, orbit position, bone formation) compared to personalised titanium implants in a repair OF defect sheep model. Implants fabrication was done using SLA of photo-crosslinkable PTMC mixed with HA [1–3]. Preclinical study: (sheep n=12, ethic number 34_2016) was conducted by first scanning the OF bone of each sheep in order to design and to fabricate patient specific implants (PSI) made of PTMC-HA. The fabricated PSI was implanted after creating OF defect. Bone formation and defect healing was compared to manually shaped titanium mesh using time-laps X-ray analyses, histology (Giemsa-Eosin staining) and sequential fluorochrome staining over 3-months. Additionally, the osteoinductive property of the biomaterials was assessed by intramuscular implantation (IM). In this study, we showed that the composite PTMC-HA allowed for ectopic bone formation after IM implantation, without requiring any biotherapeutics. In addition, we could repair OF defect on sheep using SLA-fabricated PTMC-HA with a good shape fidelity (compared to the virtual implant) and a better bone integration compared to the titanium mesh. This study opens the field of patient-specific implants made of degradable and osteoinductive scaffolds fabricated using additive manufacturing to replace advantageously autologous bone and titanium implants

The goal was to analyze the cellular response, specifically the osteogenic capacity, of titanium (Ti) implants harbouring a novel laserbased-surface-structure with the overall aim: augmented osteointegration. Surface micro-/nanoproperties greatly influence cell behaviour at the tissue-implant-interface and subsequent osteointegration. We investigated Ti-materials subjected to a specially developed shifted-Laser-Surface-Texturing (sLST) technology and compared them to a standard roughening-technique (sand-blasting-acid-etching, SLA). The biological response was evaluated with hMSCs, which are naturally available at the bone-implant-interface. We hypothesized: the novel surface is beneficial for our three different (young/healthy-YH; aged/healthy-AH;aged/osteoporotic-OP) cohorts. The sLST was performed using a SPI-G3-series laser (beam-wavelength=1064nm, pulse-duration=200ns). For the SLA surface, Ti was sandblasted, afterwards acid-etched (HCl/H2SO4). Three different hMSC cohorts were studied: YH: n=6,29±6; AH: n=5,79±5; OP: n=5,76±5 years (osteoporosis confirmed via DEXA-scan). OP hMSCs show e.g. ColI-deficient-matrix and decreased mineralization. Cells were examined for survival, cell proliferation and cytoskeleton arrangement. Osteogenic differentiation was carried out over 21 days, matrix mineralization was validated with Alizarin-Red-S-staining and quantification. Laser-texturing generated precisely the desired microgeometry. On nanostructural level, differently-sized Ti-droplets were formed stochastically by laser-induced-Ti-plasma. Live/dead-/Actin-stainings showed comparable results for all cohorts and surfaces in terms of survival and cell shape. On Ti-materials, cell growth showed no significant difference between the 3 cohorts. Alizarin quantification revealed the highest levels on laser-textured-surfaces; highest value for YH, followed by AH, lastly OP; no significance between AH/YH, but between OP/YH (p<0.0001). However, mineralization of all cohorts cultured on laser-textured-surfaces increased significantly (p<0.0001) compared to respective SLA-group, with >20fold higher value in the OP-cohort (AH:11fold, YH:6fold). The data proves the biocompatibility of the laser-structured-Ti for young+aged cohorts. Osteogenic differentiation was significantly augmented on laser-treated-Ti. Most intriguingly, OP-donors could reach manifold increased mineralization, suggesting the novel laser texturing can counteract the osteoporotic phenotype. As osteogenesis-enhancing capacities may be related to mechanisms controlling cellular shape/fate, further investigations referring to this are currently ongoing. In conclusion, our laser-textured-Ti-materials are safe, can have a demand-oriented designer-surface-topography and represent a great potential for development into next-generation-implants suitable for different patient-cohorts, especially osteoporosis patients

Abstract. Introduction. The long-term biological success of cementless orthopaedic prostheses is highly dependent on osteointegration. Pre-clinical testing of new cementless implant technology however, requires live animal testing, which has anatomical, loading, ethical and cost challenges. This proof-of-concept study aimed to develop an in vitro model to examine implant osteointegration under known loading/micromotion conditions. Methods. Fresh cancellous bone cylinders (n=8) were harvested from porcine femur and implanted with additive manufactured porous titanium implants (Ø4 × 15 mm). To simulate physiological conditions, n=3 bone cylinders were tested in a bioreactor system with a cyclic 30 µm displacement at 1Hz for 300 cycles every day for 15 days in a total of 21 days culture. The chamber was also perfused with culture medium using a peristaltic pump. Control bone cylinders were cultured under static conditions (n=5). Samples were calcein stained at day 7. Post-testing, bone cylinders were formalin fixed and bony ingrowth was measured via microscopy. Results. Viability of the freshly harvested ex vivo bone cylinders was maintained for up to 28 days. Two samples remain unanalysed due to COVID lockdown, one in each group. Similar to osteointegration seen in live animal models, evidence of bony ingrowth was seen more markedly at the bone-implant interface under dynamic conditions. This was evident by a greater intensity of calcein staining, confirming the deposition of new bone, at the bone-implant interface. In comparison, under static conditions, calcein staining was observed randomly all over the cylinder. Conclusion. This proof-of-concept study demonstrates that implant bony adaptation and ingrowth can be measured in vitro under known cyclic micromotion/loading conditions. This comparatively low cost, low ethical impact, controlled loading laboratory method has potential to accelerate the rate of implant development whilst conforming with the principles of NC3Rs. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Adhered bacteria on titanium surfaces are able to decrease its corrosion potential and impedance values at the lowest frequencies. This result points to the detrimental influence of the biofilm on the passive film formed on the surfaces, independently on the surface finishes. Titanium is one of the most used metallic biomaterials for biological and implant applications. The spontaneous formation of a protective passive film around 2–5 nm thick, make titanium unique as a biomaterial for implants. Its composition has been described by a three-layer model: TiO2/Ti2O3/TiO and its stability is ultimately responsible for the success of osseointegrated titanium implants. The cases of breakdown of the protective passive film are associated with highly acidic environments induced by bacterial biofilms and/or inflammatory processes that lead to localized corrosion of titanium and, in extreme cases, implant failure. Bearing in mind that the surface design of a titanium implant is a key element involved in the healing mechanisms at the bone-implant interface, the surface modifications have sought to enhance the biomechanical anchorage of the implant and promote osseointegration at the cell-biomolecular level. However, little attention has been paid to the effects of these surface modifications in the microbiologically induced corrosion (MIC). The aim of this work is to evaluate the potential for MIC of titanium in the short term under viable bacterial cells of Streptococcus mutansas a representative microorganism of oral biofilm considered to be a highly cariogenic pathogen. Discs of 64 mm. 2. surface area of commercially pure titanium, grade 4, were supplied by Biotechnology Institute (BTI, Vitoria, Spain). Four surface treatments were studied: two acid etchings (low roughness, opN and high roughness, opV). In addition, acid etched plus anodic oxidation (opNT). For comparative purposes, two surface finishes have been included: high roughness – corresponding with sandblasting-large grit plus acid (SLA); and, as-machined titanium (mach). The oral strain used for assessing the biofilm formation on the corrosion behavior of Ti surfaces was Streptococus mutansATCC 25175, obtained from the Spanish Type Culture Collection (CECT). The study of MIC from Streptococcus mutanson surfaces of Ti was carried out in an electrochemical cell specifically designed and patented by some of the present authors [1]. A three set up configuration of the electrochemical cell was used in the experiments. The measurement of the corrosion potential and electrochemical impedance was performed at different periods of incubation of bacteria: 2, 7, 15, 21 and 28 days. Out Slight but continuous decrease in the corrosion potential and impedance values at the lowest frequencies indicate the deleterious influence of the biofilm on the passive film formed on the surfaces, independently on the surface finishes. This research suggests that the most appropriate surface modification for the dental implant portion at the bone level would be the acid etched of high roughness (opV) surface

We implanted titanium and carbon fibre-reinforced plastic (CFRP) femoral prostheses of the same dimensions into five prosthetic femora. An abductor jig was attached and a 1 kN load applied. This was repeated with five control femora. Digital image correlation was used to give a detailed two-dimensional strain map of the medial cortex of the proximal femur. Both implants caused stress shielding around the calcar. Distally, the titanium implant showed stress shielding, whereas the CFRP prosthesis did not produce a strain pattern which was statistically different from the controls. There was a reduction in strain beyond the tip of both the implants. This investigation indicates that use of the CFRP stem should avoid stress shielding in total hip replacement

Implant infection is an increasing problem in orthopedic surgery, especially due to progressive antibiotic resistance and an aging population with rising numbers of implantations. As a consequence, new strategies for infection prevention are necessary. In the previous study it was hypothesized that laser-structured implant surfaces favor cellular adhesion while hindering bacterial ongrowth and therewith contribute to reduce implant infections. Cuboid titanium implants (0.8 × 0.8 × 12 mm. 3. , n=34) were used. Seventeen were laser-structured by ultra-short pulsed laser ablation to create a spike structure; the others were polished and served as controls. In general anesthesia, implants were inserted in rat tibiae and infected with a S. aureus suspension. During a 21 day postoperative follow-up, daily clinical control was performed. Radiographs were taken at day 14 and day 21. After euthanasia, bacterial load and biofilm formation on the implant surface was evaluated semi quantitatively by confocal laser scanning microscopy and computational acquisition of bacteria and cells by Imaris®-software. Additionally, histology of the surrounding bone was performed. Clinically, no differences were observed between the groups. However, contrary to our hypothesis, bacterial load was increased in the laser-structured implant group although cellular adhesion was even more pronounced. Radiographical and histological evaluations showed increased bone alterations in the group with laser-structured implants compared to the control group. These findings did not confirm prior in vitro studies, where a reduction of bacterial load was found for similar surfaces and demonstrate the necessity of in vivo trials prior to the clinical use of new materials

Summary Statement. The modulation of both quantity and quality of peri-implant bone with either PTH or loading may be viable options to improve implant fixation and patient outcomes. A strong bone-implant interface is essential for successful joint replacement surgery. This study investigated the differences in bone surrounding and within a porous titanium implant after single or combined treatment with two anabolic bone therapies: intermittent parathyroid hormone (teriparatide) and mechanical loading. Porous titanium implants were inserted bilaterally on the distal lateral femurs of rabbits. The right implant was loaded daily (1 MPa, 50 cycles/day) while the left implant was not. Rabbits received daily PTH injections (20 ug/kg) or saline vehicle. Periprosthetic cancellous bone 0.5, 1.0, and 2.0 mm below the implant surface, bone at the 0.25 mm bone-implant interface and total bone within each implant were examined using tissue-level analyses (quantitative backscattered electron microscopy), cellular analyses (immunohistochemistry staining of osteoblasts with procollagen-1 and TRAP staining of osteoclasts), and shear testing (implant-bone interface). Statistical significance was determined using GEE models (p<0.05). For tissue located 0.5 mm below the implant, significant increases in bone area per total area (BA/TA) were observed with PTH treatment (56%) and with loading (27%). Further, an 18% increase in mineralization density with PTH treatment and a 20% increase in mineralization density with loading was found. Loading effects were not present beyond the 0.5 mm periprosthetic region, but PTH significantly increased BA/TA 2.0 mm below and mineralization density 1.0 mm below the implant. Tissue-level changes were supported by increases in osteoblast activity 0.5 mm below the implant with PTH (79%) and loading (34%), as well as by minimal osteoclast changes. At the 0.25 mm implant-bone interface PTH and loading increased BA/TA (16% and 23%, respectively), but only loading increased mineralization density (7%). Further, total integrated bone area was increased 35% with PTH. Both PTH and loading enhanced the mechanical integrity of the implant-bone; shear strength increased 34% and 60%, respectively. Although combined treatment was not synergistic, both PTH and loading individually enhanced the amount and mineralization density of bone at the implant interface and immediately below the interface, thereby increasing the mechanical strength of the metal-bone interface. This research suggests that modulation of both quantity and quality of peri-implant bone may be viable options to improve implant fixation and patient outcomes