Biomimetic HA-GO implant coating for enhanced osseointegration via macrophage M2 polarization-induced osteo-immunomodulation.

The pro-inflammatory/anti-inflammatory polarized phenotypes of macrophages (M1/M2) can be used to predict the success of implant integration. Hence, activating and inducing the transformation of immunocytes that promote tissue repair appears to be a highly promising strategy for facilitating osteo-anagenesis. In a previous study, titanium implants were coated with a graphene oxide-hydroxyapatite (GO-HA) nanocomposite via electrophoretic deposition, and the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was found to be significantly enhanced when the GO content was 2wt%. However, the effectiveness of the GO-HA nanocomposite coating in modifying the in vivo immune microenvironment still remains unclear. In this study, the effects of GO-HA coatings on osteogenesis were investigated based on the GO-HA-mediated immune regulation of macrophages. The HA-2wt%GO nanocomposite coatings exhibited good biocompatibility and favored M2 macrophage polarization. Meanwhile, they could also significantly upregulate IL-10 (anti-inflammatory factor) expression and downregulate TNF-α (pro-inflammatory factor) expression. Additionally, the microenvironment, which was established by M2 macrophages, favored the osteogenesis of BMSCs both in vivo and in vitro. These findings show that the GO-HA nanocomposite coating is a promising surface-modification material. Hence, this study provides a reference for the development of next-generation osteoimmunomodulatory biomaterials.

Mesoscale characterization of osseointegration around an additively manufactured genistein-coated implant.

Given the hierarchical nature of bone and bone interfaces, osseointegration, namely the formation of a direct bone-implant contact, is best evaluated using a multiscale approach. However, a trade-off exists between field of view and spatial resolution, making it challenging to image large volumes with high resolution. In this study, we combine established electron microscopy techniques to probe bone-implant interfaces at the microscale and nanoscale with plasma focused ion beam-scanning electron microscopy (PFIB-SEM) tomography to evaluate osseointegration at the mesoscale. This characterization workflow is demonstrated for bone response to an additively manufactured Ti-6Al-4V implant which combines engineered porosity to facilitate bone ingrowth and surface functionalization via genistein, a phytoestrogen, to counteract bone loss in osteoporosis. SEM demonstrated new bone formation at the implant site, including in the internal implant pores. At the nanoscale, scanning transmission electron microscopy and energy-dispersive X-ray spectroscopy confirmed the gradual nature of the bone-implant interface. By leveraging mesoscale analysis with PFIB-SEM tomography that captures large volumes of bone-implant interface with nearly nanoscale resolution, the presence of mineral ellipsoids varying in size and orientation was revealed. In addition, a well-developed lacuno-canalicular network and mineralization fronts directed both towards the implant and away from it were highlighted.

THE IMPACT OF SYSTEMIC DRUGS ON DENTAL IMPLANT OSSEOINTEGRATION: A REVIEW.

The process of osteointegration of dental implants is a biological process. Systemic therapy can interfere with this process, affecting the growth and breakdown processes of the bone and ultimately leading to implant failure. This literature review focuses on specific groups of systemic drugs that directly impact osteointegration. The research in electronic literature was conducted using the National Library of Medicine's PubMed/MEDLINE database from March 2000 to February 2024. The following MeSH (Medical Subject Headings) terms were used: "implant osseointegration," "bisphosphonates," "non-steroidal anti-inflammatory drugs," "glucocorticoids," "proton pump inhibitors," and "selective serotonin reuptake inhibitors (SSRIs)." This search yielded 1,258 articles on implant osseointegration. Among these, 30 articles met our criteria for implant osseointegration and bisphosphonates, 2 articles for non-steroidal anti-inflammatory drugs (NSAIDs), 7 articles for glucocorticoids, 14 articles for proton pump inhibitors (PPIs), and 14 articles for selective serotonin reuptake inhibitors (SSRIs). Clinicians considering implant therapy should be mindful of potential medication-related implant failures. The present systematic review has identified an association between proton pump inhibitors (PPIs), nonsteroidal anti-inflammatory drugs (NSAIDs), selective serotonin reuptake inhibitors (SSRIs), glucocorticoids, and bisphosphonates with an increased implant failure rate.

Beyond microroughness: novel approaches to navigate osteoblast activity on implant surfaces.

Considering the biological activity of osteoblasts is crucial when devising new approaches to enhance the osseointegration of implant surfaces, as their behavior profoundly influences clinical outcomes. An established inverse correlation exists between osteoblast proliferation and their functional differentiation, which constrains the rapid generation of a significant amount of bone. Examining the surface morphology of implants reveals that roughened titanium surfaces facilitate rapid but thin bone formation, whereas smooth, machined surfaces promote greater volumes of bone formation albeit at a slower pace. Consequently, osteoblasts differentiate faster on roughened surfaces but at the expense of proliferation speed. Moreover, the attachment and initial spreading behavior of osteoblasts are notably compromised on microrough surfaces. This review delves into our current understanding and recent advances in nanonodular texturing, meso-scale texturing, and UV photofunctionalization as potential strategies to address the "biological dilemma" of osteoblast kinetics, aiming to improve the quality and quantity of osseointegration. We discuss how these topographical and physicochemical strategies effectively mitigate and even overcome the dichotomy of osteoblast behavior and the biological challenges posed by microrough surfaces. Indeed, surfaces modified with these strategies exhibit enhanced recruitment, attachment, spread, and proliferation of osteoblasts compared to smooth surfaces, while maintaining or amplifying the inherent advantage of cell differentiation. These technology platforms suggest promising avenues for the development of future implants.

Osteoporotic osseointegration: therapeutic hallmarks and engineering strategies.

Osteoporosis is a systemic skeletal disease caused by an imbalance between bone resorption and formation. Current treatments primarily involve systemic medication and hormone therapy. However, these systemic treatments lack directionality and are often ineffective for locally severe osteoporosis, with the potential for complex adverse reactions. Consequently, treatment strategies using bioactive materials or external interventions have emerged as the most promising approaches. This review proposes twelve microenvironmental treatment targets for osteoporosis-related pathological changes, including local accumulation of inflammatory factors and reactive oxygen species (ROS), imbalance of mitochondrial dynamics, insulin resistance, disruption of bone cell autophagy, imbalance of bone cell apoptosis, changes in neural secretions, aging of bone cells, increased local bone tissue vascular destruction, and decreased regeneration. Additionally, this review examines the current research status of effective or potential biophysical and biochemical stimuli based on these microenvironmental treatment targets and summarizes the advantages and optimal parameters of different bioengineering stimuli to support preclinical and clinical research on osteoporosis treatment and bone regeneration. Finally, the review addresses ongoing challenges and future research prospects.

Osteointegration of functionalised high-performance oxide ceramics: imaging from micro-computed tomography.

BACKGROUND: This study evaluated the osseointegration potential of functionalised high-performance oxide ceramics (HPOC) in isolation or coated with BMP-2 or RGD peptides in 36 New Zeeland female rabbits using micro-computed tomography (micro CT). The primary outcomes of interest were to assess the amount of ossification evaluating the improvement in the bone volume/ total volume (BV/TV) ratio and trabecular thickness at 6 and 12 weeks. The second outcome of interest was to investigate possible differences in osteointegration between the functionalised silanised HPOC in isolation or coated with Bone Morphogenetic Protein 2 (BMP-2) or RGD peptides. METHODS: 36 adult female New Zealand white rabbits with a minimum weight of three kg were used. One-third of HPOCs were functionalised with silicon suboxide (SiOx), a third with BMP-2 (sHPOC-BMP2), and another third with RGD (sHPOC-RGD). All samples were scanned with a high-resolution micro CT (U-CTHR, MILabs B.V., Houten, The Netherlands) with a reconstructed voxel resolution of 10 µm. MicroCT scans were reconstructed in three planes and processed using Imalytics Preclinical version 2.1 (Gremse-IT GmbH, Aachen, Germany) software. The total volume (TV), bone volume (BV) and ratio BV/TV were calculated within the coating area. RESULTS: BV/TV increased significantly from 6 to 12 weeks in all HPOCs: silanised (P = 0.01), BMP-2 (P < 0.0001), and RGD (P < 0.0001) groups. At 12 weeks, the BMP-2 groups demonstrated greater ossification in the RGD (P < 0.0001) and silanised (P = 0.008) groups. Trabecular thickness increased significantly from 6 to 12 weeks (P < 0.0001). At 12 weeks, BMP-2 promoted greater trabecular thickness compared to the silanised group (P = 0.07), although no difference was found with the RGD (P = 0.1) group. CONCLUSION: Sinalised HPOC in isolation or functionalised with BMP-2 or RGD promotes in vivo osteointegration. The sinalised HOPC functionalised with BMP-2 demonstrated the greatest osseointegration.

Nanofeatured surfaces in dental implants: contemporary insights and impending challenges.

Dental implant therapy, established as standard-of-care nearly three decades ago with the advent of microrough titanium surfaces, revolutionized clinical outcomes through enhanced osseointegration. However, despite this pivotal advancement, challenges persist, including prolonged healing times, restricted clinical indications, plateauing success rates, and a notable incidence of peri-implantitis. This review explores the biological merits and constraints of microrough surfaces and evaluates the current landscape of nanofeatured dental implant surfaces, aiming to illuminate strategies for addressing existing impediments in implant therapy. Currently available nanofeatured dental implants incorporated nano-structures onto their predecessor microrough surfaces. While nanofeature integration into microrough surfaces demonstrates potential for enhancing early-stage osseointegration, it falls short of surpassing its predecessors in terms of osseointegration capacity. This discrepancy may be attributed, in part, to the inherent "dichotomy kinetics" of osteoblasts, wherein increased surface roughness by nanofeatures enhances osteoblast differentiation but concomitantly impedes cell attachment and proliferation. We also showcase a controllable, hybrid micro-nano titanium model surface and contrast it with commercially-available nanofeatured surfaces. Unlike the commercial nanofeatured surfaces, the controllable micro-nano hybrid surface exhibits superior potential for enhancing both cell differentiation and proliferation. Hence, present nanofeatured dental implants represent an evolutionary step from conventional microrough implants, yet they presently lack transformative capacity to surmount existing limitations. Further research and development endeavors are imperative to devise optimized surfaces rooted in fundamental science, thereby propelling technological progress in the field.

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.

TNF-α-licensed exosome-integrated titaniumaccelerated T2D osseointegration by promoting autophagy-regulated M2 macrophage polarization.

Type 2 diabetes (T2D) is on a notable rise worldwide, which leads to unfavorable outcomes during implant treatments. Surface modification of implants and exosome treatment have been utilized to enhance osseointegration. However, there has been insufficient approach to improve adverse osseointegration in T2D conditions. In this study, we successfully loaded TNF-α-treated mesenchymal stem cell (MSC)-derived exosomes onto micro/nano-network titanium (Ti) surfaces. TNF-α-licensed exosome-integrated titanium (TNF-exo-Ti) effectively enhanced M2 macrophage polarization in hyperglycemic conditions, with increased secretion of anti-inflammatory cytokines and decreased secretion of pro-inflammatory cytokines. In addition, TNF-exo-Ti pretreated macrophage further enhanced angiogenesis and osteogenesis of endothelial cells and bone marrow MSCs. More importantly, TNF-exo-Ti markedly promoted osseointegration in T2D mice. Mechanistically, TNF-exo-Ti activated macrophage autophagy to promote M2 polarization through inhibition of the PI3K/AKT/mTOR pathway, which could be abolished by PI3K agonist. Thus, this study established TNF-α-licensed exosome-immobilized titanium surfaces that could rectify macrophage immune states and accelerate osseointegration in T2D conditions.

Nano-Based Approaches in Surface Modifications of Dental Implants: A Literature Review.

Rehabilitation of fully or partially edentulous patients with dental implants represents one of the most frequently used surgical procedures. The work of Branemark, who observed that a piece of titanium embedded in rabbit bone became firmly attached and difficult to remove, introduced the concept of osseointegration and revolutionized modern dentistry. Since then, an ever-growing need for improved implant materials towards enhanced material-tissue integration has emerged. There is a strong belief that nanoscale materials will produce a superior generation of implants with high efficiency, low cost, and high volume. The aim of this review is to explore the contribution of nanomaterials in implantology. A variety of nanomaterials have been proposed as potential candidates for implant surface customization. They can have inherent antibacterial properties, provide enhanced conditions for osseointegration, or act as reservoirs for biomolecules and drugs. Titania nanotubes alone or in combination with biological agents or drugs are used for enhanced tissue integration in dental implants. Regarding immunomodulation and in order to avoid implant rejection, titania nanotubes, graphene, and biopolymers have successfully been utilized, sometimes loaded with anti-inflammatory agents and extracellular vesicles. Peri-implantitis prevention can be achieved through the inherent antibacterial properties of metal nanoparticles and chitosan or hybrid coatings bearing antibiotic substances. For improved corrosion resistance various materials have been explored. However, even though these modifications have shown promising results, future research is necessary to assess their clinical behavior in humans and proceed to widespread commercialization.

Comparative evaluation of osseodensification drilling versus conventional drilling technique on dental implant stability: A systematic review.

AIM: The present systematic review compares the stability, crestal bone levels and efficacy of osseodensification (OD) drilling techniques for dental implant placement to traditional drilling methods. SETTINGS AND DESIGN: The Cochrane online library, PubMed, Scopus, and other well-known online resources are used in the research. Using a systematic review design, the current study examines published qualitative studies with an emphasis on analysis. MATERIALS AND METHODS: Using precise keywords, a thorough search of pertinent databases was carried out in accordance with PRISMA standards. Studies testing dental implant stability, crestal bone levels and clinical results using both OD and traditional procedures were covered by the inclusion criteria. STATISTICAL ANALYSIS USED: The risk of bias and quality of included studies was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias tool for randomized controlled trials. RESULTS: A total of 170 patients and 334 implants from Egypt, India, and Brazil were included in eight papers that made up the systematic review. In several clinical situations, osseodensification outperformed standard drilling in terms of implant durability, bone development, and torque data. Statistical analysis presented the lowest risks, while blinded outcome assessment, allocation concealment, random sequence generation, incomplete outcome data and experimental technique revealed higher risks. Bias assessment found various risks across different components. CONCLUSION: The thorough examination of eight papers demonstrates that osseodensification is a technique with great promise in the field of dental implants. It exhibits superior torque values, bone development, and stability when compared to traditional drilling. The overall results highlight the potential of osseodensification to improve clinical outcomes and advance the science of dental implantology, even in the face of variances in bias concerns.

Effect of different occlusal materials on peri-implant stress distribution with different osseointegration condition: A finite element analysis.

AIM: Studies have not been done to evaluate the peri-implant stress exerted by materials(like PEEK and resin matrix ceramics) in different osseointegration conditions. To investigate the effect of different occlusal materials on peri-implant stress distribution with different osseointegration condition using finite element analysis. SETTINGS AND DESIGN: Eighteen different 3D FEA models of implant fixed with abutment were created involving 6 different occlusal materials (Heat cured temporary acrylic resin (PMMA), Bis-GMA, PEEK, Lithium disilicate, Resin matrix ceramics and translucent Zirconia) and different osseointegrated conditions (50%, 75%, 100%). MATERIALS AND METHODS: Models were subjected to loading vertically and obliquely followed by evaluation of stress distribution. STATISTICAL ANALYSIS USED: The results of the simulation obtained were analysed in terms of Von mises, maximum principal and minimal principal stresses using descriptive stastistics. RESULTS: PMMA (40.14 MPa on vertical loading and 66 MPa on oblique loading) resulted in the highest stresses and lithium disilicate (24 MPa on vertical loading and 52.40 MPa on oblique loading) resulted in least stresses among all the crown materials. Upon oblique loading, von Mises stress increases except for translucent zirconia and lithium disilicate (52.444 MPa on 50%, 47.733 MPa on 75%, and 43.973 MPa on 100% osseointegration). Minimal principal stress values decreased with increase in osseointegration upon oblique loading for PMMA, BisGMA, and PEEK. CONCLUSION: Translucent zirconia and lithium disilicate offer a better stress transmission. Minimal principal stress values of PEEK and BisGMA decreased with increasing osseointegration.

Team Approach: Osseointegration Amputation Surgery.

¼ The purpose of this article was to review the multidisciplinary, team-based approach necessary for the optimal management of patients with limb loss undergoing osseointegration surgery.¼ In this study, we describe the interdisciplinary process of screening, counseling, and surgical and rehabilitation considerations with an emphasis on principles rather than specific implants or techniques.¼ Integrated perioperative management and long-term surveillance are crucial to ensure the best possible outcomes.¼ We hope this model will service as an implant-agnostic guide to others seeking to development an osseointegration center of excellence.

A microtomographic and histopathological evaluation of dental cements as late-stage peri-implant complication in a rat model.

Cement mediated peri-implantitis accounts for 1.9-75% of dental implant failures associated with peri-implant diseases. This study evaluated the biological impact of dental cements on osseointegrated implants using Lewis rats. Twenty-two rats were distributed into 6 groups: negative control (NC) soft diet (SD), and hard diet (HD); positive control SD and HD (n = 3); Implant + bio-ceramic Cement (BC) SD and HD which included contralateral Sham sites (n = 5). Titanium implants were placed on either side of the maxillae and allowed to heal for 14 days. Later, both sides of experimental groups underwent a re-entry surgery to simulate clinical cementation. The right side received 0.60 mg of BC. At 14 days post cement application, maxillae were harvested for clinical, microtomographic, and histological evaluations. Clinical and microtomographic evaluations indicated evidence of extensive inflammation and circumferential bone resorption around BC implants in comparison to NC. Histology revealed cement particles surrounded by inflammatory infiltrate in the implant area accompanied by biofilm for SD groups. Both sides of BC indicated intensive bone resorption accompanied by signs of osteolysis when compared to NC. Cemented groups depicted significantly lower bone to implant contact when compared to NC. In conclusion, residual cement extravasation negatively impacted osseointegrated implants after re-entry surgeries.

Electrical Responsive Coating with a Multilayered TiO2-SnO2-RuO2 Heterostructure on Ti for Controlling Antibacterial Ability and Improving Osseointegration.

The bacterial infection and poor osseointegration of Ti implants could significantly compromise their applications in bone repair and replacement. Based on the carrier separation ability of the heterojunction and the redox reaction of pseudocapacitive metal oxides, we report an electrically responsive TiO2-SnO2-RuO2 coating with a multilayered heterostructure on a Ti implant. Owing to the band gap structure of the TiO2-SnO2-RuO2 coating, electron carriers are easily enriched at the coating surface, enabling a response to the endogenous electrical stimulation of the bone. With the formation of SnO2-RuO2 pseudocapacitance on the modified surface, the postcharging mode can significantly change the surface chemical state of the coating due to the redox reaction, enhancing the antibacterial ability and osteogenesis-related gene expression of the human bone marrow mesenchymal stem cells. Owing to the attraction for Ca2+, only the negatively postcharged SnO2@RuO2 can promote apatite deposition. The in vivo experiment reveals that the S-SnO2@RuO2-NP could effectively kill the bacteria colonized on the surface and promote osseointegration with the synostosis bonding interface. Thus, negatively charging the electrically responsive coating of TiO2-SnO2-RuO2 is a good strategy to endow modified Ti implants with excellent antibacterial ability and osseointegration.

The Addition of Hydroxyapatite Nanoparticles on Implant Surfaces Modified by Zirconia Blasting and Acid Etching to Enhance Peri-Implant Bone Healing.

This study investigated the impact of adding hydroxyapatite nanoparticles to implant surfaces treated with zirconia blasting and acid etching (ZiHa), focusing on structural changes and bone healing parameters in low-density bone sites. The topographical characterization of titanium discs with a ZiHa surface and a commercially modified zirconia-blasted and acid-etched surface (Zi) was performed using scanning electron microscopy, profilometry, and surface-free energy. For the in vivo assessment, 22 female rats were ovariectomized and kept for 90 days, after which one implant from each group was randomly placed in each tibial metaphysis of the animals. Histological and immunohistochemical analyses were performed at 14 and 28 days postoperatively (decalcified lab processing), reverse torque testing was performed at 28 days, and histometry from calcified lab processing was performed at 60 days The group ZiHa promoted changes in surface morphology, forming evenly distributed pores. For bone healing, ZiHa showed a greater reverse torque, newly formed bone area, and bone/implant contact values compared to group Zi (p < 0.05; t-test). Qualitative histological and immunohistochemical analyses showed higher features of bone maturation for ZiHa on days 14 and 28. This preclinical study demonstrated that adding hydroxyapatite to zirconia-blasted and acid-etched surfaces enhanced peri-implant bone healing in ovariectomized rats. These findings support the potential for improving osseointegration of dental implants, especially in patients with compromised bone metabolism.

Influence of the Surface Topography of Titanium Dental Implants on the Behavior of Human Amniotic Stem Cells.

The dental implant surface plays a crucial role in osseointegration. The topography and physicochemical properties will affect the cellular functions. In this research, four distinct titanium surfaces have been studied: machined acting (MACH), acid etched (AE), grit blasting (GBLAST), and a combination of grit blasting and subsequent acid etching (GBLAST + AE). Human amniotic mesenchymal (hAMSCs) and epithelial stem cells (hAECs) isolated from the amniotic membrane have attractive stem-cell properties. They were cultured on titanium surfaces to analyze their impact on biological behavior. The surface roughness, microhardness, wettability, and surface energy were analyzed using interferometric microscopy, Vickers indentation, and drop-sessile techniques. The GBLAST and GBLAST + AE surfaces showed higher roughness, reduced hydrophilicity, and lower surface energy with significant differences. Increased microhardness values for GBLAST and GBLAST + AE implants were attributed to surface compression. Cell viability was higher for hAMSCs, particularly on GBLAST and GBLAST + AE surfaces. Alkaline phosphatase activity enhanced in hAMSCs cultured on GBLAST and GBLAST + AE surfaces, while hAECs showed no mineralization signals. Osteogenic gene expression was upregulated in hAMSCs on GBLAST surfaces. Moreover, α2 and ß1 integrin expression enhanced in hAMSCs, suggesting a surface-integrin interaction. Consequently, hAMSCs would tend toward osteoblastic differentiation on grit-blasted surfaces conducive to osseointegration, a phenomenon not observed in hAECs.

Osteointegration of Ti Bone Implants: A Study on How Surface Parameters Control the Foreign Body Response.

The integration of titanium (Ti)-based implants with bone is limited, resulting in implant failure. This lack of osteointegration is due to the foreign body response (FBR) that occurs after the implantation of biodevices. The process begins with protein adsorption, which is governed by implant surface properties, e.g., chemistry, charge, wettability, and/or topography. The distribution and composition of the protein layer in turn influence the recruitment, differentiation, and modulation of immune and bone cells. The subsequent events that occur at the bone-material interface will ultimately determine whether the implant is encapsulated or will integrate with bone. Despite the numerous studies evaluating the influence of surface properties in the various stages of the FBR, the factors that affect tissue-material interactions are often studied in isolation or in small correlations due to the technical challenges involved in assessing them in vitro or in vivo. Consequently, the influence of protein conformation on the Ti bone implant surface design remains an unresolved research question. The objective of this review is to comprehensively evaluate the existing literature on the effect of surface parameters of Ti and its alloys in the stages of FBR, with a particular focus on protein adsorption and osteoimmunomodulation. This evaluation aims to systematically describe these effects on bone formation.

Validation of IMU against optical reference and development of open-source pipeline: proof of concept case report in a participant with transfemoral amputation fitted with a Percutaneous Osseointegrated Implant.

BACKGROUND: Systems that capture motion under laboratory conditions limit validity in real-world environments. Mobile motion capture solutions such as Inertial Measurement Units (IMUs) can progress our understanding of "real" human movement. IMU data must be validated in each application to interpret with clinical applicability; this is particularly true for diverse populations. Our IMU analysis method builds on the OpenSim IMU Inverse Kinematics toolkit integrating the Versatile Quaternion-based Filter and incorporates realistic constraints to the underlying biomechanical model. We validate our processing method against the reference standard optical motion capture in a case report with participants with transfemoral amputation fitted with a Percutaneous Osseointegrated Implant (POI) and without amputation walking over level ground. We hypothesis that by using this novel pipeline, we can validate IMU motion capture data, to a clinically acceptable degree. RESULTS: Average RMSE (across all joints) between the two systems from the participant with a unilateral transfemoral amputation (TFA) on the amputated and the intact sides were 2.35° (IQR = 1.45°) and 3.59° (IQR = 2.00°) respectively. Equivalent results in the non-amputated participant were 2.26° (IQR = 1.08°). Joint level average RMSE between the two systems from the TFA ranged from 1.66° to 3.82° and from 1.21° to 5.46° in the non-amputated participant. In plane average RMSE between the two systems from the TFA ranged from 2.17° (coronal) to 3.91° (sagittal) and from 1.96° (transverse) to 2.32° (sagittal) in the non-amputated participant. Coefficients of Multiple Correlation (CMC) results between the two systems in the TFA ranged from 0.74 to > 0.99 and from 0.72 to > 0.99 in the non-amputated participant and resulted in 'excellent' similarity in each data set average, in every plane and at all joint levels. Normalized RMSE between the two systems from the TFA ranged from 3.40% (knee level) to 54.54% (pelvis level) and from 2.18% to 36.01% in the non-amputated participant. CONCLUSIONS: We offer a modular processing pipeline that enables the addition of extra layers, facilitates changes to the underlying biomechanical model, and can accept raw IMU data from any vendor. We successfully validate the pipeline using data, for the first time, from a TFA participant using a POI and have proved our hypothesis.