The Application Progress of Nonthermal Plasma Technology in the Modification of Bone Implant Materials.

With the accelerating trend of global aging, bone damage caused by orthopedic diseases, such as osteoporosis and fractures, has become a shared international event. Traffic accidents, high-altitude falls, and other incidents are increasing daily, and the demand for bone implant treatment is also growing. Although extensive research has been conducted in the past decade to develop medical implants for bone regeneration and healing of body tissues, due to their low biocompatibility, weak bone integration ability, and high postoperative infection rates, pure titanium alloys, such as Ti-6A1-4V and Ti-6A1-7Nb, although widely used in clinical practice, have poor induction of phosphate deposition and wear resistance, and Ti-Zr alloy exhibits a lack of mechanical stability and processing complexity. In contrast, the Ti-Ni alloy exhibits toxicity and low thermal conductivity. Nonthermal plasma (NTP) has aroused widespread interest in synthesizing and modifying implanted materials. More and more researchers are using plasma to modify target catalysts such as changing the dispersion of active sites, adjusting electronic properties, enhancing metal carrier interactions, and changing their morphology. NTP provides an alternative option for catalysts in the modification processes of oxidation, reduction, etching, coating, and doping, especially for materials that cannot tolerate thermodynamic or thermosensitive reactions. This review will focus on applying NTP technology in bone implant material modification and analyze the overall performance of three common types of bone implant materials, including metals, ceramics, and polymers. The challenges faced by NTP material modification are also discussed.

Semi-quantitative analysis on sea buckthorn phenolic-rich extract coating bone-like open porous NiTi-based alloy.

This study investigates the feasibility of coating Ni-Ti alloy with sea buckthorn extract via a hydrothermal method for targeted delivery of beneficial phenolic compounds to bone tissue. The qualitative analysis confirmed the presence of flavonoids and tannins in sea buckthorn extract, supporting its osteogenic potential. The microhardness of the NiTi alloy substrate was suitable for biomedical applications, and successful coating was achieved without compromising its properties. NiTi alloy samples were coated with 18.1, 20.1, and 12.4 mg of extract, respectively. Comprehensive evaluations confirmed the successful integration of the extract onto the alloy's surface. The coated system exhibited sustained release properties over five days, with the highest release occurring on the first day (on average 32.1 % for the first peak and 72.1 % for the second peak), as determined by HPLC analysis. The findings demonstrate the potential of this novel approach in developing dual-functionality implants for bone health promotion. Overall, this study underscores the promising potential of Ni-Ti alloy coated with sea buckthorn extract as a targeted drug delivery system for bone tissue.

Evaluating the Feasibility of Short Dental Implants as Alternatives to Long Dental Implants in Mandibular Bone: A Finite Element Study.

This study uses finite element analysis to investigate the potential application of shorter dental implants as a substitute for longer implants in the lower jaw (mandible). FEA allows the evaluation of the stress patterns around the implant-bone interface, a critical factor for successful osseointegration. Ten models were generated, encompassing five long (L1-L5) and five short implant models (S1-S5) with variations in diameter and length. Hypermesh software was utilized to meticulously prepare the FEA models, ensuring accurate mesh generation. The FEA simulations were conducted under four distinct loading scenarios (100 N occlusal load, 40 N lateral load, 100 N oblique at 30°, and 100 N oblique at 45°) to realistically mimic the forces exerted during biting, using an ABAQUS CAE solver. The results revealed that the von Mises stress generated within the short implant models was demonstrably lower compared to their long implants. Additionally, a significant drop in stress was observed with increasing the diameter of the short implants, to a certain diameter range. These findings suggest the potential for successful substitution of long implant model L4 with short implant model S4 due to the demonstrably lower stress values achieved. Furthermore, the data indicates the possibility of utilizing short implant models S3 and S5 as alternatives to long implant models L3 and L5, respectively. These observations hold significant promise for evaluating the feasibility of replacing long implants with shorter variants, potentially leading to a reduction in implant-related failures.

Computational biomechanical study on hybrid implant materials for the femoral component of total knee replacements.

Multifunctional materials have been described to meet the diverse requirements of implant materials for femoral components of uncemented total knee replacements. These materials aim to combine the high wear and corrosion resistance of oxide ceramics at the joint surfaces with the osteogenic potential of titanium alloys at the bone-implant interface. Our objective was to evaluate the biomechanical performance of hybrid material-based femoral components regarding mechanical stress within the implant during cementless implantation and stress shielding (evaluated by strain energy density) of the periprosthetic bone during two-legged squat motion using finite element modeling. The hybrid materials consisted of alumina-toughened zirconia (ATZ) ceramic joined with additively manufactured Ti-6Al-4V or Ti-35Nb-6Ta alloys. The titanium component was modeled with or without an open porous surface structure. Monolithic femoral components of ATZ ceramic or Co-28Cr-6Mo alloy were used as reference. The elasticity of the open porous surface structure was determined within experimental compression tests and was significantly higher for Ti-35Nb-6Ta compared to Ti-6Al-4V (5.2 ± 0.2 GPa vs. 8.8 ± 0.8 GPa, p < 0.001). During implantation, the maximum stress within the ATZ femoral component decreased from 1568.9 MPa (monolithic ATZ) to 367.6 MPa (Ti-6Al-4V/ATZ), 560.9 MPa (Ti-6Al-4V/ATZ with an open porous surface), 474.9 MPa (Ti-35Nb-6Ta/ATZ), and 648.4 MPa (Ti-35Nb-6Ta/ATZ with an open porous surface). The strain energy density increased at higher flexion angles for all models during the squat movement. At ∼90° knee flexion, the strain energy density in the anterior region of the distal femur increased by 25.7 % (Ti-6Al-4V/ATZ), 70.3 % (Ti-6Al-4V/ATZ with an open porous surface), 43.7 % (Ti-35Nb-6Ta/ATZ), and 82.5% (Ti-35Nb-6Ta/ATZ with an open porous surface) compared to monolithic ATZ. Thus, the hybrid material-based femoral component decreases the intraoperative fracture risk of the ATZ part and considerably reduces the risk of stress shielding of the periprosthetic bone.

Sheep Bone Ultrastructure Analyses Reveal Differences in Bone Maturation around Mg-Based and Ti Implants.

Magnesium alloys are some of the most convenient biodegradable materials for bone fracture treatment due to their tailorable degradation rate, biocompatibility, and mechanical properties resembling those of bone. Despite the fact that magnesium-based implants and ZX00 (Mg-0.45Zn-0.45Ca in wt.%), in particular, have been shown to have suitable degradation rates and good osseointegration, knowledge gaps remain in our understanding of the impact of their degradation properties on the bone's ultrastructure. Bone is a hierarchically structured material, where not only the microstructure but also the ultrastructure are important as properties like the local mechanical response are determined by it. This study presents the first comparative analysis of bone ultrastructure parameters with high spatial resolution around ZX00 and Ti implants after 6, 12, and 24 weeks of healing. The mineralization was investigated, revealing a significant decrease in the lattice spacing of the (002) Bragg's peak closer to the ZX00 implant in comparison to Ti, while no significant difference in the crystallite size was observed. The hydroxyapatite platelet thickness and osteon density demonstrated a decrease closer to the ZX00 implant interface. Correlative indentation and strain maps obtained by scanning X-ray diffraction measurements revealed a higher stiffness and faster mechanical adaptation of the bone surrounding Ti implants as compared to the ZX00 ones. Thus, the results suggest the incorporation of Mg2+ ions into the bone ultrastructure, as well as a lower degree of remodeling and stiffness of the bone in the presence of ZX00 implants than Ti.

Effect of Different Administered Doses of Capsaicin and Titanium Implant Osseointegration.

Background and Objectives: This study aimed to evaluate the histological and biochemical effects of capsaicin on implant osseointegration and oxidative stress. Materials and Methods: Male Wistar albino rats weighing between 250 and 300 g were used in this study. Twenty-four rats were randomly divided into three equal groups: implant + control (n = 8), implant + capsaicin-1 (n = 8), and implant + capsaicin-2 (n = 8). Additionally, 2.5 mm diameter and 4 mm length titanium implants were surgically integrated into the corticocancellous bone parts of the femurs. In the treatment groups, rats were injected intraperitoneally with 25 mg/kg (implant + capsaicin-1) and 50 mg/kg (implant + capsaicin-2) of capsaicin. No additional applications were made in the control group. Three rats in total died during and after the experiment as a result of the analyses performed on 21 animals. Results: The highest total antioxidant status value was found in capsaicin dose 2, according to the analysis. The control group had the highest total oxidant status and oxidative stress index values, while group 2 of capsaicin had the lowest. After analysis, we found that there was no observed positive effect on osteointegration in this study (p > 0.05), although the bone implant connection was higher in the groups treated with capsaicin. Conclusions: A positive effect on osteointegration was not observed in this study. This may be due to osteoclast activation. However, it was found that it has a positive effect on oxidative stress. Osteoclast activation may be the cause of this phenomenon. Capsaicin was found to have a positive effect on oxidative stress (p < 0.05). It was also observed to have a positive effect on oxidative stress.

Biomechanical Behavior of Injected Cement Spacers versus Traditional Cages in Low-Density Lumbar Spine under Compression Loading.

Background and Objectives: Osteoporosis renders the use of traditional interbody cages potentially dangerous given the high risk of damage in the bone-implant interface. Instead, injected cement spacers can be applied as interbody devices; however, this technique has been mainly used in cervical spine surgery. This study aimed at investigating the biomechanical behavior of cement spacers versus traditional cages in lumbar spine surgery. Materials and Methods: Destructive monotonic axial compression testing was performed on 20 human cadaveric low-density lumbar segments from elderly donors (14 f/6 m, 70.3 ± 12.0 y) treated with either injected cement spacers (n = 10) or traditional cages (n = 10) without posterior instrumentation. Stiffness, failure load and displacement were compared. The effects of bone density, vertebral geometry and spacer contact area were evaluated. Results: Cement spacers demonstrated higher stiffness, significantly smaller displacement (p < 0.001) and a similar failure load compared to traditional cages. In the cage group, stiffness and failure load depended strongly on bone density and vertebral height, whereas failure displacement depended on vertebral anterior height. No such correlations were identified with cement spacers. Conclusions: Cement spacers used in lumbar interbody stabilization provided similar compression strength, significantly smaller failure displacement and a stiffer construct than traditional cages that provided benefits mainly for large and strong vertebrae. Cement stabilization was less sensitive to density and could be more beneficial also for segments with smaller and less dense vertebrae. In contrast to the injection of cement spacers, the optimal insertion of cages into the irregular intervertebral space is challenging and risks damaging bone. Further studies are required to corroborate these findings and the treatment selection thresholds.

Effects of antiseptic irrigation solutions on osseointegration in a cementless tibial implantation mouse model.

Despite the success of standard antiseptic irrigation solutions in reducing periprosthetic joint infection (PJI) rates, there is still a need for more effective solutions. Synergistic use of povidone-iodine (PI) and hydrogen peroxide (H2O2) has shown promising results; however, the optimal solution concentration balancing bactericidal activity and osseointegration remains unknown. This study aims to evaluate the impact of these antiseptic irrigation solutions on osseointegration and the bone-implant interface strength in vivo. Forty C57BL/6 mice underwent bilateral tibial implantation surgery and were randomly allocated into three groups receiving 0.3% PI, 10% PI mixed with 3% H2O2, or saline as irrigation solutions intraoperatively. Assessments were performed on postoperative Days 1 and 28, including plain radiographs, microcomputed tomography (microCT) evaluation, histological analysis, immunohistochemistry, and biomechanical pull-out testing. No wound complications were observed. MicroCT scans revealed no differences in peri-implant trabecular bone parameters. Biomechanical pull-out testing showed no differences in the bone-implant interface strength across groups. Histological analysis indicated no differences in bone and bone marrow percentage areas among treatment groups. Immunohistochemical analysis demonstrated no differences among groups in peri-implant osteocalcin, osterix, or endomucin-positive cells. In conclusion, using either antiseptic irrigation solution showed no differences in osseointegration parameters compared to the control group, demonstrating safety and the absence of toxicity. CLINICAL RELEVANCE: Dilute 0.3% povidone-iodine and a 1:1 combination of 10% povidone-iodine mixed with 3% hydrogen peroxide can be safely used during primary and revision total joint arthroplasty without compromising osseointegration or causing wound complications.

Ceramic Implant Rehabilitation: Consensus Statements from Joint Congress for Ceramic Implantology: Consensus Statements on Ceramic Implant.

The objectives of the study group focused on the following main topics related to the performance of 1- and 2-piece ceramic implants: defining bone-implant-contact percentages and its measurement methods, evaluating the pink esthetic score as an esthetic outcome parameter after immediate implantation, recognizing the different results of ceramic implant designs as redefined by the German Association of Oral Implantology, incorporating the patient report outcome measure to include satisfaction and improvement in oral health-related quality of life, and conducting preclinical studies to address existing gaps in ceramic implants. During the Joint Congress for Ceramic Implantology (2022), the study group evaluated 17 clinical trials published between 2015 and 2021. After extensive discussions and multiple closed sessions, consensus statements and recommendations were developed, incorporating all approved modifications. A 1-piece implant design features a coronal part that is fused to the implant body or interfaces with the postabutment restoration platform, undergoing transmucosal healing. Long-term evaluations of this implant design are supported by established favorable clinical evidence. Inaccuracies in the pink esthetic score and bone-implant-contact percentages were managed by establishing control groups for preclinical studies and randomizing clinical trials. The patient-reported outcome measures were adjusted to include an individual visual analog scale, collected from each clinical study, that quantified improved oral health and quality of life. Preclinical investigations should focus on examining the spread of ceramic debris and the impact of heat generation on tissue and cellular levels during drilling. Further technical advancements should prioritize wound management and developing safe drilling protocols.

Effects of the Application Local Zoledronic Acid On Different Dental Implants in Rats On Osseointegration.

Objective: Recently, a lot of research has been done around the world to popularize the osseointegration of dental implants. In this study, it was investigated the effect of local zoledronic acid application on implants with machined (MAC), resorbable blast materials (RBM), sandblasted and acid-etched (SLA) surface implants integrated in rat tibias. Methodology: A total of 60 female Wistar rats weighing between 270 and 300 g were used in the study. The rats were passing divided into six classes: controls; MAC (n = 10), RBM (n = 10), SLA (n = 10), and local zoledronic acid (LZA) applied groups; LZA-MAC (n = 10), LZA-RBM (n=10) and LZA-SLA (n = 10) and implants were surgically placement into rat tibias in general anesthesia. After a four-week experimental period, the biomechanical bone implant connection level was determined with reverse torque analysis. Results: Osseointegration levels were detected highly in SLA and RBM surface compared with the machined surfaced implants in both control and treatment groups (p < 0.05). Additionally, local application of zoledronic acid in both three groups; implants increased the biomechanic osseointegration level compared with the controls (p < 0.05). Conclusion: In this research, we observe that the local application of the zoledronic acid could increase the osseointegration, and RBM and SLA surface could be better than machined surfaced implants in terms of bone implant connection. In addition, local application of zoledronic acid may be a safer method than systemic application.

Nanoscale osseointegration of zirconia evaluated from the interfacial structure between ceria-stabilized tetragonal zirconia and cell-induced hydroxyapatite.

BACKGROUND: The osseointegration of zirconia implants has been evaluated based on their implant fixture bonding with the alveolar bone at the optical microscopic level. Achieving nano-level bonding between zirconia and bone apatite is crucial for superior osseointegration; however, only a few studies have investigated nanoscale bonding. This review outlines zirconia osseointegration, including surface modification, and presents an evaluation of nanoscale zirconia-apatite bonding and its structure. HIGHLIGHT: Assuming osseointegration, the cells produced calcium salts on a ceria-stabilized zirconia substrate. We analyzed the interface between calcium salts and zirconia substrates using transmission electron microscopy and found that 1) the cell-induced calcium salts were bone-like apatite and 2) direct nanoscale bonding was observed between the bone-like apatite and zirconia crystals without any special modifications of the zirconia surface. CONCLUSION: Structural affinity exists between bone apatite and zirconia crystals. Apatite formation can be induced by the zirconia surface. Zirconia bonds directly with apatite, indicating superior osseointegration in vivo.

Implant surface modifications and their impact on osseointegration and peri-implant diseases through epigenetic changes: A scoping review.

Dental implant surfaces and their unique properties can interact with the surrounding oral tissues through epigenetic cues. The present scoping review provides current perspectives on surface modifications of dental implants, their impact on the osseointegration process, and the interaction between implant surface properties and epigenetics, also in peri-implant diseases. Findings of this review demonstrate the impact of innovative surface treatments on the epigenetic mechanisms of cells, showing promising results in the early stages of osseointegration. Dental implant surfaces with properties of hydrophilicity, nanotexturization, multifunctional coatings, and incorporated drug-release systems have demonstrated favorable outcomes for early bone adhesion, increased antibacterial features, and improved osseointegration. The interaction between modified surface morphologies, different chemical surface energies, and/or release of molecules within the oral tissues has been shown to influence epigenetic mechanisms of the surrounding tissues caused by a physical-chemical interaction. Epigenetic changes around dental implants in the state of health and disease are different. In conclusion, emerging approaches in surface modifications for dental implants functionalized with epigenetics have great potential with a significant impact on modulating bone healing during osseointegration.

Surface modification of a commercial bone plate (Ti6Al4V) implant for improved antibacterial and cytocompatibility via thermal dewetting of a silver thin film.

The high demand for bone grafts has motivated the development of implants with excellent osteogenic activity, whereas the risk of implant-associated infection, particularly given the rise of antimicrobial resistance, has compelled the development of implants with innovative antimicrobial strategies in which a small amount of bactericidal agent can effectively kill a wide range of bacteria. To induce antibacterial property, the surface of Grade-5 bone plate titanium implants used in clinical applications was modified using direct current (DC) sputter coating followed by thermal annealing. The 15 nm silver film-coated implants were thermally annealed in the furnace for 15 min at 750 °C. The modified implant surface's antibacterial efficacy againstEscherichia coli(E. coli),Staphylococcus aureus(S. aureus),Salmonella typhi, andMethicillin-resistant staphylococcus aureusbacteria has been assessed using a colony-forming assay. On the modified implant surface, the growth ofE. coliandS. aureusbacteria is reduced by 99.72%, while highly drug-resistant bacteria are inhibited by 96.59%. The MTT assay was used to assess the cytotoxicity of the modified bone-implant surface against NIH3T3 mouse fibroblast cells. The modified bone-implant surface promoted fibroblast growth and demonstrated good cytocompatibility. Furthermore, the mechanical properties of the implant were not harmed by this novel surface modification method. This method is simple and provides new insight into surface modification of commercial metallic implants to have effective antibacterial properties against various classes of bacteria.

3D Printing of a Porous Zn-1Mg-0.1Sr Alloy Scaffold: A Study on Mechanical Properties, Degradability, and Biosafety.

In recent years, the use of zinc (Zn) alloys as degradable metal materials has attracted considerable attention in the field of biomedical bone implant materials. This study investigates the fabrication of porous scaffolds using a Zn-1Mg-0.1Sr alloy through a three-dimensional (3D) printing technique, selective laser melting (SLM). The results showed that the porous Zn-1Mg-0.1Sr alloy scaffold featured a microporous structure and exhibited a compressive strength (CS) of 33.71 ± 2.51 MPa, a yield strength (YS) of 27.88 ± 1.58 MPa, and an elastic modulus (E) of 2.3 ± 0.8 GPa. During the immersion experiments, the immersion solution showed a concentration of 2.14 ± 0.82 mg/L for Zn2+ and 0.34 ± 0.14 mg/L for Sr2+, with an average pH of 7.61 ± 0.09. The porous Zn-1Mg-0.1Sr alloy demonstrated a weight loss of 12.82 ± 0.55% and a corrosion degradation rate of 0.36 ± 0.01 mm/year in 14 days. The Cell Counting Kit-8 (CCK-8) assay was used to check the viability of the cells. The results showed that the 10% and 20% extracts significantly increased the activity of osteoblast precursor cells (MC3T3-E1), with a cytotoxicity grade of 0, which indicates safety and non-toxicity. In summary, the porous Zn-1Mg-0.1Sr alloy scaffold exhibits outstanding mechanical properties, an appropriate degradation rate, and favorable biosafety, making it an ideal candidate for degradable metal bone implants.

3-D finite element model of the impaction of a press-fitted femoral stem under various biomechanical environments.

BACKGROUND: Uncemented femoral stem insertion into the bone is achieved by applying successive impacts on an inserter tool called "ancillary". Impact analysis has shown to be a promising technique to monitor the implant insertion and to improve its primary stability. METHOD: This study aims to provide a better understanding of the dynamic phenomena occurring between the hammer, the ancillary, the implant and the bone during femoral stem insertion, to validate the use of impact analyses for implant insertion monitoring. A dynamic 3-D finite element model of the femoral stem insertion via an impaction protocol is proposed. The influence of the trabecular bone Young's modulus (Et), the interference fit (IF), the friction coefficient at the bone-implant interface (µ) and the impact velocity (v0) on the implant insertion and on the impact force signal is evaluated. RESULTS: For all configurations, a decrease of the time difference between the two first peaks of the impact force signal is observed throughout the femoral stem insertion, up to a threshold value of 0.23 ms. The number of impacts required to reach this value depends on Et, v0 and IF and varies between 3 and 8 for the set of parameters considered herein. The bone-implant contact ratio reached after ten impacts varies between 60% and 98%, increases as a function of v0 and decreases as a function of IF, µ and Et. CONCLUSION: This study confirms the potential of an impact analyses-based method to monitor implant insertion and to retrieve bone-implant contact properties.

Implant Strength Contributes to the Osseointegration Strength of Porous Metallic Materials.

Creating the optimal environment for effective and long term osseointegration is a heavily researched and sought-after design criteria for orthopedic implants. A validated multimaterial finite element (FE) model was developed to replicate and understand the results of an experimental in vivo push-out osseointegration model. The FE model results closely predicted global force (at 0.5 mm) and stiffness for the 50-90% porous implants with an r2 of 0.97 and 0.98, respectively. In addition, the FE global force at 0.5 mm showed a correlation to the maximum experimental forces with an r2 of 0.90. The highest porosity implants (80-90%) showed lower stiffnesses and more equitable load sharing but also failed at lower a global force level than the low porosity implants (50-70%). The lower strength of the high porosity implants caused premature plastic deformation of the implant itself during loading as well as significant deformations in the ingrown and surrounding bone, resulting in lower overall osseointegration strength, consistent with experimental measurements. The lower porosity implants showed a balance of sufficient bony ingrowth to support osseointegration strength coupled with implant mechanical properties to circumvent significant implant plasticity and collapse under the loading conditions. Together, the experimental and finite element modeling results support an optimal porosity in the range of 60-70% for maximizing osseointegration with current structure and loading.

Strategies for Improving Impaired Osseointegration in Compromised Animal Models.

Implant osseointegration is reduced in patients with systemic conditions that compromise bone quality, such as osteoporosis, disuse syndrome, and type 2 diabetes. Studies using rodent models designed to mimic these compromised conditions demonstrated reduced bone-to-implant contact (BIC) or a decline in bone mineral density. These adverse effects are a consequence of disrupted intercellular communication. A variety of approaches have been developed to compensate for the altered microenvironment inherent in compromised conditions, including the use of biologics and implant surface modification. Chemical and physical modification of surface properties at the microscale, mesoscale, and nanoscale levels to closely resemble the surface topography of osteoclast resorption pits found in bone has proven to be a highly effective strategy for improving implant osseointegration. The addition of hydrophilicity to the surface further enhances osteoblast response at the bone-implant interface. These surface modifications, applied either alone or in combination, improve osseointegration by increasing proliferation and osteoblastic differentiation of osteoprogenitor cells and enhancing angiogenesis while modulating osteoclast activity to achieve net new bone formation, although the specific effects vary with surface treatment. In addition to direct effects on surface-attached cells, the communication between bone marrow stromal cells and immunomodulatory cells is sensitive to these surface properties. This article reports on the advances in titanium surface modifications, alone and in combination with novel therapeutics in animal models of human disease affecting bone quality. It offers clinically translatable perspectives for clinicians to consider when using different surface modification strategies to improve long-term implant performance in compromised patients. This review supports the use of surface modifications, bioactive coatings, and localized therapeutics as pragmatic approaches to improve BIC and enhance osteogenic activity from both structural and molecular standpoints.

The effect and mechanism of liraglutide on the biological functions of BMSCs in diabetic patients.

OBJECTIVES: To investigate the effect of liraglutide on osteogenesis in human alveolar bone marrow mesenchymal stem cells (BMSCs) and the influence of liraglutide on implant-bone integration in rats with T2DM. SUBJECTS AND METHODS: Extracting BMSCs from the alveoli of diabetic patients treated with insulin. BMSCs were treated with different concentrations of liraglutide. Osteogenesis and the underlying mechanism were investigated via ALP detection, ALP staining, Alizarin Red S staining, Western blotting, and RT-PCR. Liraglutide was given to Wistar and GK rats after implantation, and new bone formation around the implants was analyzed via micro-CT. Implant-bone integration in rats was investigated via toluidine blue staining. RESULTS: Liraglutide enhanced osteogenesis in BMSCs via the BMP2/Smad/Runx2 signaling pathway. The optimal concentration of liraglutide that promoted osteogenesis was 10-8 mol/L. At concentrations higher than 10-7 mol/L, liraglutide had a negative effect on BMSCs. At a concentration of 10-8 mol/L liraglutide, BMSCs and diabetes mellitus-bone marrow stromal cells (DM-BMSCs) showed optimal osteogenesis. Liraglutide promoted implant-bone integration and new bone formation in Wistar and GK rats. CONCLUSIONS: Liraglutide not only promotes osteogenesis of BMSCs in normoglycemic individuals but also enhances osteogenesis of BMSCs in diabetic patients treated with insulin and enhances osseointegration in rats.

A novel computational workflow to holistically assess total knee arthroplasty biomechanics identifies subject-specific effects of joint mechanics on implant fixation.

Computational studies of total knee arthroplasty (TKA) often focus on either joint mechanics (kinematics and forces) or implant fixation mechanics. However, such disconnect between joint and fixation mechanics hinders our understanding of overall TKA biomechanical function by preventing identification of key relationships between these two levels of TKA mechanics. We developed a computational workflow to holistically assess TKA biomechanics by integrating musculoskeletal and finite element (FE) models. For our initial study using the workflow, we investigated how tibiofemoral contact mechanics affected the risk of failure due to debonding at the implant-cement interface using the four available subjects from the Grand Challenge Competitions to Predict In Vivo Knee Loads. We used a musculoskeletal model with a 12 degrees-of-freedom knee joint to simulate the stance phase of gait for each subject. The computed tibiofemoral joint forces at each node in contact were direct inputs to FE simulations of the same subjects. We found that the peak risk of failure did not coincide with the peak joint forces or the extreme tibiofemoral contact positions. Moreover, despite the consistency of joint forces across subjects, we observed important variability in the profile of the risk of failure during gait. Thus, by a combined evaluation of the joint and implant fixation mechanics of TKA, we could identify subject-specific effects of joint kinematics and forces on implant fixation that would otherwise have gone unnoticed. We intend to apply our workflow to evaluate the impact of implant alignment and design on TKA biomechanics.

A scoring system to evaluate stability of percutaneous osseointegrated implants for transfemoral amputation with validation in the ITAP clinical trial.

Percutaneous osseointegrated implants for individuals with lower limb amputation can increase mobility, reduce socket related pain, and improve quality of life. It would be useful to have an evaluation method to assess the interface between bone and implant. We assessed outpatient radiographs from the Intraosseous Transcutaneous Amputation Prosthesis clinical trial using an interface scoring system which summed and weighted equally measures of implant collar cortical ongrowth and radiolucency along the implant stem/bone interface. Radiographs from 12 participants with unilateral transfemoral amputations (10 males, 2 females, mean age = 43.2, SD = 7.4 years) in the clinical trial from cohort I (implanted in 2008/09) or cohort II (implanted in 2013/14) were collated (mean image span = 7.2, SD = 2.4 years), scale normalised, zoned, and measured in a repeatable way. Interface scores were calculated and then compared to clinical outcomes. Explanted participants received the lowest interface scores. A higher ratio of stem to residuum and shorter residuum's produced better interface scores and there was an association (weak correlation) between participants with thin cortices and the lowest interface scores. A tapered, cemented, non curved stem may provide advantageous fixation while stem alignment did not appear critical. In summary, the interface score successfully demonstrated a non-invasive evaluation of percutaneous osseointegrated implants interfaces when applied to the Intraosseous Transcutaneous Amputation Prosthesis clinical trial. The clinical significance of this work is to identify events leading to aseptic or septic implant removal and contribute to clinical guidelines for monitoring rehabilitation, design and surgical fixation choices.