Harmonic Vibration Analysis in a Simplified Model for Monitoring Transfemoral Implant Loosening.

A simplified axisymmetric model of a transfemoral osseointegration implant was used to investigate the influence of the contact condition at the bone-implant interface on the vibrational response. The experimental setup allowed the degree of implant tightness to be controlled using a circumferential compression device affixed to the bone. Diametrically placed sensors allowed torsional modes to be distinguished from flexural modes. The results showed that the structural resonant frequencies did not shift significantly with tightness levels. The first torsional mode of vibration was found to be particularly sensitive to interface loosening. Harmonics in the vibrational response became prominent when the amplitude of the applied torque increased beyond a critical level. The torque level at which the third harmonic begins to rise correlated with implant criticality, suggesting a potential strategy for early detection of implant loosening based on monitoring the amplitude of the third harmonic of the torsional mode.

A millimetre-scale capacitive biosensing and biophysical stimulation system for emerging bioelectronic bone implants.

Bioelectronic bone implants are being widely recognized as a promising technology for highly personalized bone/implant interface sensing and biophysical therapeutic stimulation. Such bioelectronic devices are based on an innovative concept with the ability to be applied to a wide range of implants, including in fixation and prosthetic systems. Recently, biointerface sensing using capacitive patterns was proposed to overcome the limitations of standard imaging technologies and other non-imaging technologies; moreover, electric stimulation using capacitive patterns was proposed to overcome the limitations of non-instrumented implants. We here provide an innovative low-power miniaturized electronic system with ability to provide both therapeutic stimulation and bone/implant interface monitoring using network-architectured capacitive interdigitated patterns. It comprises five modules: sensing, electric stimulation, processing, communication and power management. This technology was validated using in vitro tests: concerning the sensing system, its ability to detect biointerface changes ranging from tiny to severe bone-implant interface changes in target regions was validated; concerning the stimulation system, its ability to significantly enhance bone cells' full differentiation, including matrix maturation and mineralization, was also confirmed. This work provides an impactful contribution and paves the way for the development of the new generation of orthopaedic biodevices.

Adding mechanobiological cell features to finite element analysis of an immediately loaded dental implant.

Finite element analysis (FEA) has been used to analyze the behavior of dental materials, mainly in implantology. However, FEA is a mechanical analysis and few studies have tried to simulate the biological characteristics of the healing process of loaded implants. This study used the rule of mixtures to simulate the biological healing process of immediate implants in an alveolus socket and bone-implant junction interface through FEA. Three-dimensional geometric models of the structures were obtained, and material properties were derived from the literature. The rule of mixtures was used to simulate the healing periods-immediate and early loading, in which the concentration of each cell type, based on in vivo studies, influenced the final elastic moduli. A 100 N occlusal load was simulated in axial and oblique directions. The models were evaluated for maximum and minimum principal strains, and the bone overload was assessed through Frost's mechanostat. There was a higher strain concentration in the healing regions and cortical bone tissue near the cervical portion. The bone overload was higher in the immediate load condition. The method used in this study may help to simulate the biological healing process and could be useful to relate FEA results to clinical practice.

Biomimicking Bone-Implant Interface Facilitates the Bioadaption of a New Degradable Magnesium Alloy to the Bone Tissue Microenvironment.

The most critical factor determining the success of biodegradable bone implants is the host tissue response, which greatly depends on their degradation behaviors. Here, a new magnesium-based implant, namely magnesium-silicon-calcium (Mg-0.2Si-1.0Ca) alloy, that coordinates its biodegradation along with the bone regenerative process via a self-assembled, multilayered bone-implant interface is designed. At first, its rapid biocorrosion contributes to a burst release of Mg2+ , leading to a pro-osteogenic immune microenvironment in bone. Meanwhile, with the simultaneous intervention of Ca and Si in the secondary phases of the new alloy, a hierarchical layered calcified matrix is rapidly formed at the degrading interface that favored the subsequent bone mineralization. In contrast, pure Mg or Mg-0.2Si alloy without the development of this interface at the beginning will unavoidably induce detrimental bone loss. Hence, it is believed this biomimicking interface justifies its bioadaptability in which it can modulate its degradation in vivo and accelerate bone mineralization.

The limit of tolerable micromotion for implant osseointegration: a systematic review.

Much research effort is being invested into the development of porous biomaterials that enhance implant osseointegration. Large micromotions at the bone-implant interface impair this osseointegration process, resulting in fibrous capsule formation and implant loosening. This systematic review compiled all the in vivo evidence available to establish if there is a universal limit of tolerable micromotion for implant osseointegration. The protocol was registered with the International Prospective Register for Systematic Reviews (ID: CRD42020196686). Pubmed, Scopus and Web of Knowledge databases were searched for studies containing terms relating to micromotion and osseointegration. The mean value of micromotion for implants that osseointegrated was 32% of the mean value for those that did not (112 ± 176 µm versus 349 ± 231 µm, p < 0.001). However, there was a large overlap in the data ranges with no universal limit apparent. Rather, many factors were found to combine to affect the overall outcome including loading time, the type of implant and the material being used. The tables provided in this review summarise these factors and will aid investigators in identifying the most relevant micromotion values for their biomaterial and implant development research.

Inhibition of Sirtuin 3 prevents titanium particle-induced bone resorption and osteoclastsogenesis via suppressing ERK and JNK signaling.

Implant-derived wear particles can be phagocytosed by local macrophages, triggering an inflammatory cascade that can drive the activation and recruitment of osteoclasts, thereby inducing peri-prosthetic osteolysis. Efforts to suppress pro-inflammatory cytokine release and osteoclastsogenesis thus represent primary approaches to treating and preventing such osteolysis. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylases that control diverse metabolic processes. However, whether SIRT3 could mitigate wear debris-induced osteolysis has not been reported. Herein we explored the impact of the SIRT3 on titanium particle-induced osteolysis. Tartrate resistant acid phosphatase (TRAP) staining revealed that the inhibition of SIRT3 suppressed nuclear factor-κB ligand (RANKL)-mediated osteoclasts activation in a dose-dependent fashion. Notably, inhibition of SIRT3 also suppressed matrix metallopeptidase 9 (MMP9) and nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) expression at the mRNA and protein levels, while also inhibiting the mRNA expression of dendritic cell-specific transmembrane protein (DC-STAMP), ATPase H+ Transporting V0 Subunit D2 (Atp6v0d2), TRAP and Cathepsin K (CTSK) . In addition, inhibition of SIRT3 suppressed titanium particle-induced tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) expression and prevented titanium particle-induced osteolysis and bone loss in vivo. This inhibition of osteoclasts differentiation was found to be linked to the downregulation and reduced phosphorylation of JNK and ERK. Taken together, inhibition of SIRT3 may be a potential target for titanium particle-induced bone loss.

In vivo performance of Al2O3-Ti bone implants in the rat femur.

BACKGROUND: Alumina-titanium (Al2O3-Ti) biocomposites have been recently developed with improved mechanical properties for use in heavily loaded orthopedic sites. Their biological performance, however, has not been investigated yet. METHODS: The aim of the present study was to evaluate the in vivo biological interaction of Al2O3-Ti. Spark plasma sintering (SPS) was used to fabricate Al2O3-Ti composites with 25 vol.%, 50 vol.%, and 75 vol.% Ti content. Pure alumina and titanium were also fabricated by the same procedure for comparison. The fabricated composite disks were cut into small bars and implanted into medullary canals of rat femurs. The histological analysis and scanning electron microscopy (SEM) observation were carried out to determine the bone formation ability of these materials and to evaluate the bone-implant interfaces. RESULTS: The histological observation showed the formation of osteoblast, osteocytes with lacuna, bone with lamellar structures, and blood vessels indicating that the healing and remodeling of the bone, and vasculature reconstruction occurred after 4 and 8 weeks of implantation. However, superior bone formation and maturation were obtained after 8 weeks. SEM images also showed stronger interfaces at week 8. There were differences between the composites in percentages of bone area (TB%) and the number of osteocytes. The 50Ti composite showed higher TB% at week 4, while 25Ti and 75Ti represented higher TB% at week 8. All the composites showed a higher number of osteocytes compared to 100Ti, particularly 75Ti. CONCLUSIONS: The fabricated composites have the potential to be used in load-bearing orthopedic applications.

An experimental study on stress-shielding effects of locked compression plates in fixing intact dog femur.

BACKGROUND: In orthopedic application, stress-shielding effects of implant materials cause bone loss, which often induces porosis, delayed bone healing, and other complications. We aimed to compare the stress-shielding effects of locked compression plate (LCP) and limited-contact dynamic compression plate (LC-DCP) in dogs with plate-fixed femurs. METHODS: Bilateral intact femurs of 24 adult dogs were fixed by adult forearm 9-hole titanium plates using minimally invasive plate osteosynthesis (MIPPO) technology, with LCP on the left and LC-DCP on the right femurs. Dogs were sacrificed at 6 weeks, 12 weeks, and 24 weeks after surgery, and bone specimens were used to evaluate the efficacies of different fixing methods on bones through X-ray, dual-energy X-ray absorptiometry (DEXA), histology, MicroCT, and biomechanics analyses. RESULTS: X-ray results showed significant callus formation and periosteal reaction in the LC-DCP group. Bone cell morphology, degree of osteoporosis, and bone mineral density (BMD) changes of the LCP group were significantly better than that of the LC-DCP group. MicroCT results showed that the LCP group had significantly reduced degree of cortical bone osteoporosis than the LC-DCP group. Tissue mineral density (TMD) in the LCP group was higher than that in the LC-DCP group at different time points (6 weeks, 12 weeks, and 24 weeks). Biomechanics analyses demonstrated that the compressive strength and flexural strength of bones fixed by LCP were better than that by LC-DCP. CONCLUSIONS: Stress-shielding effects of LCP are significantly weaker than that of LC-DCP, which is beneficial to new bone formation and fracture healing, and LCP can be widely used in clinic for fracture fixation.

Osteocytes Influence on Bone Matrix Integrity Affects Biomechanical Competence at Bone-Implant Interface of Bioactive-Coated Titanium Implants in Rat Tibiae.

Osseointegration is a prerequisite for the long-term success of implants. Titanium implants are preferred for their biocompatibility and mechanical properties. Nonetheless, the need for early and immediate loading requires enhancing these properties by adding bioactive coatings. In this preclinical study, extracellular matrix properties and cellular balance at the implant/bone interface was examined. Polyelectrolyte multilayers of chitosan and gelatin or with chitosan and Hyaluronic acid fabricated on titanium alloy using a layer-by-layer self-assembly process were compared with native titanium alloy. The study aimed to histologically evaluate bone parameters that correlate to the biomechanical anchorage enhancement resulted from bioactive coatings of titanium implants in a rat animal model. Superior collagen fiber arrangements and an increased number of active osteocytes reflected a significant improvement of bone matrix quality at the bone interface of the chitosan/gelatin-coated titan implants over chitosan/hyaluronic acid-coated and native implants. Furthermore, the numbers and localization of osteoblasts and osteoclasts in the reparative and remodeling phases suggested a better cellular balance in the chitosan/Gel-coated group over the other two groups. Investigating the micro-mechanical properties of bone tissue at the interface can elucidate detailed discrepancies between different promising bioactive coatings of titanium alloys to maximize their benefit in future medical applications.

Biomechanical evaluation of total ankle arthroplasty. Part II: Influence of loading and fixation design on tibial bone-implant interaction.

Finite element (FE) models to evaluate the burden placed on the interaction between total ankle arthroplasty (TAA) implants and the bone often rely on peak axial forces. However, the loading environment of the ankle is complex, and it is unclear whether peak axial forces represent a challenging scenario for the interaction between the implant and the bone. Our goal was to determine how the loads and the design of the fixation of the tibial component of TAA impact the interaction between the implant and the bone. To this end, we developed a framework that integrated robotic cadaveric simulations to determine the ankle kinematics, musculoskeletal models to determine the ankle joint loads, and FE models to evaluate the interaction between TAA and the bone. We compared the bone-implant micromotion and the risk of bone failure of three common fixation designs for the tibial component of TAA: spikes, a stem, and a keel. We found that the most critical conditions for the interaction between the implant and the bone were dependent on the specimen and the fixation design, but always involved submaximal forces and large moments. We also found that while the fixation design influenced the distribution and the peak value of bone-implant micromotion, the amount of bone at risk of failure was specimen dependent. To account for the most critical conditions for the interaction between the implant and the bone, our results support simulating multiple specimens under complex loading profiles that include multiaxial moments and span entire activity cycles.

Replicating dynamic humerus motion using an industrial robot.

Transhumeral percutaneous osseointegrated prostheses provide upper-extremity amputees with increased range of motion, more natural movement patterns, and enhanced proprioception. However, direct skeletal attachment of the endoprosthesis elevates the risk of bone fracture, which could necessitate revision surgery or result in loss of the residual limb. Bone fracture loads are direction dependent, strain rate dependent, and load rate dependent. Furthermore, in vivo, bone experiences multiaxial loading. Yet, mechanical characterization of the bone-implant interface is still performed with simple uni- or bi-axial loading scenarios that do not replicate the dynamic multiaxial loading environment inherent in human motion. The objective of this investigation was to reproduce the dynamic multiaxial loading conditions that the humerus experiences in vivo by robotically replicating humeral kinematics of advanced activities of daily living typical of an active amputee population. Specifically, 115 jumping jack, 105 jogging, 15 jug lift, and 15 internal rotation trials-previously recorded via skin-marker motion capture-were replicated on an industrial robot and the resulting humeral trajectories were verified using an optical tracking system. To achieve this goal, a computational pipeline that accepts a motion capture trajectory as input and outputs a motion program for an industrial robot was implemented, validated, and made accessible via public code repositories. The industrial manipulator utilized in this study was able to robotically replicate over 95% of the aforementioned trials to within the characteristic error present in skin-marker derived motion capture datasets. This investigation demonstrates the ability to robotically replicate human motion that recapitulates the inertial forces and moments of high-speed, multiaxial activities for biomechanical and orthopaedic investigations. It also establishes a library of robotically replicated motions that can be utilized in future studies to characterize the interaction of prosthetic devices with the skeletal system, and introduces a computational pipeline for expanding this motion library.

Upper extremity prosthetic selection influences loading of transhumeral osseointegrated systems.

Percutaneous osseointegrated (OI) implants are increasingly viable as an alternative to socket suspension of prosthetic limbs. Upper extremity prostheses have also become more complex to better replicate hand and arm function and attempt to recreate pre-amputation functional levels. With more functionality comes heavier devices that put more stress on the bone-implant interface, which could be an issue for implant stability. This study quantified transhumeral loading at defined amputation levels using four simulated prosthetic limb-types: (1) body powered hook, (2) myoelectric hook, (3) myoelectric hand, and (4) advanced prosthetic limb. Computational models were constructed to replicate the weight distribution of each prosthesis type, then applied to motion capture data collected during Advanced Activities of Daily Living (AADLs). For activities that did not include a handheld weight, the body powered prosthesis bending moments were 13-33% (range of means for each activity across amputation levels) of the intact arm moments (reference 100%), torsional moments were 12-15%, and axial pullout forces were 30-40% of the intact case (p≤0.001). The myoelectric hook and hand bending moments were 60-99%, torsional moments were 44-97%, and axial pullout forces were 62-101% of the intact case. The advanced prosthesis bending moments were 177-201%, torsional moments were 164-326%, and axial pullout forces were 133-185% of the intact case (p≤0.001). The addition of a handheld weight for briefcase carry and jug lift activities reduced the overall impact of the prosthetic model itself, where the body powered forces and moments were much closer to those of the intact model, and more complex prostheses further increased forces and moments beyond the intact arm levels. These results reveal a ranked order in loading magnitude according to complexity of the prosthetic device, and highlight the importance of considering the patient's desired terminal device when planning post-operative percutaneous OI rehabilitation and training.

Reengineering Bone-Implant Interfaces for Improved Mechanotransduction and Clinical Outcomes.

The number of patients undergoing joint replacement surgery has progressively increased worldwide due to world population ageing. In the Unites States, for example, the prevalence of hip and knee replacements has increased more than 6 and 10 times, respectively, since 1980. Despite advances in orthopaedic implant research, including the development of novel implantable biomaterials, failures are still observed due to inadequate biomechanical compliance at the bone-implant interface. This comprises static and dynamic mechanical mismatch between the bone and the implant surface. The importance and robustness of biomechanical cues for controlling osteogenic differentiation of mesenchymal stem cells (MSC) have been highlighted in recent studies. However, in the context of bone regenerative medicine, it remains elusive how mechanobiological signals controlling MSC osteogenic differentiation dynamics are modulated in their interaction with the bone and with implants. In this review, we highlight recent technological advances aiming to improve host bone-implant interactions based on the osteogenic and mechanoresponsive potential of MSC, in the context of joint replacement surgery. First, we discuss the extracellular and intracellular mechanical forces underlying proper receptivity and stimulation of physiological MSC differentiation and linked osteogenic activity. Second, we provide a critical overview on how this knowledge can be integrated towards the development of biomaterials for improved bone-implant interfaces. Third, we discuss cross-disciplinarily which contributes to the next generation design of novel pro-active orthopaedic implants and their implantation success. Graphical Abstract.

Comparison of bone-to-implant contact and bone volume around implants placed with or without site preparation: a histomorphometric study in rabbits.

The objective of this in vivo study was to compare bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) values of a new implant, designed to be inserted without bone preparation, using two different preparation protocols: no site preparation and prior limited cortical perforation, versus the values of a control implant using a conventional drilling protocol. Forty-one implants were inserted in 13 rabbits. Thirteen test implants with a new thread design were inserted using no bone preparation (NP), 14 test implants were inserted with limited cortical perforation (CP), and 14 conventional implants served as control. Five animals were sacrificed after 21 days and eight animals after 42 days. Histomorphometric analysis was performed and percentage of BIC and BAFO values were measured. ANOVA with Tukey post hoc and Mann-Whitney nonparametric tests were calculated to compare between the groups. Statistical analysis showed no significant difference in the measured values between any of the groups, neither compered by implant nor by compered day. The results demonstrated that biological osseointegration parameters of implant that was inserted without any bone preparation was non-inferior compared to conventional preparation. The clinical relevance is that novel implant designs may not require bone preparation prior to placement.

Bone Marrow Mesenchymal Stromal Cells (BMMSCs) Augment Osteointegration of Dental Implants in Type 1 Diabetic Rabbits: An X-Ray Micro-Computed Tomographic Evaluation.

Background and objectives: The study aimed to investigate the effect of bone marrow mesenchymal stromal cells (BMMSCs) on implant-bone osseointegration in type I diabetic New Zealand rabbits. Materials and methods: BMMSCs harvested from healthy rabbits were processed and validated for purity and osteocyte differentiability. Mandibular incisors of diabetic and control rabbits were carefully extracted, and the sockets were plugged with collagen sponges. Platelet-rich plasma (PRP) containing osteoinductive BMMSCs, and plain PRP were injected into the collagen sponge of the right and left sockets respectively. Dental implants of 2.6 mm diameter and 10 mm length were inserted into the collagen sponge of both sockets. All the animals were sacrificed six weeks post surgery to evaluate an early stage of osseointegration; the mandibles scanned by X-ray microcomputed tomography (µCT) and subjected to 3D analysis. The µCT parameters of the right implant were paired against that of the left side of each animal and analyzed by paired T-test. Results: The preclinical evaluation of the viability and osteocyte differentiation of the BMMSCs were consistent between both the donor samples. The osseointegration of dental implants with stem cell therapy (BMMSCs + PRP + collagen) in normal and diabetic rabbits was significantly higher than that of implants with adjunctive PRP + collagen only (p < 0.05). Conclusion: Stem Cell therapy with osteoinductive BMMSCs and PRP can offer a novel approach to enhance the osseointegration of dental implants in uncontrolled diabetic patients.

Ultrasonic Propagation in a Dental Implant.

Ultrasound techniques can be used to characterize and stimulate dental implant osseointegration. However, the interaction between an ultrasonic wave and the implant-bone interface (IBI) remains unclear. This study-combining experimental and numerical approaches-investigates the propagation of an ultrasonic wave in a dental implant by assessing the amplitude of the displacements along the implant axis. An ultrasonic transducer was excited in a transient regime at 10 MHz. Laser interferometric techniques were employed to measure the amplitude of the displacements, which varied 3.2-8.9 nm along the implant axis. The results demonstrated the propagation of a guided wave mode along the implant axis. The velocity of the first arriving signal was equal to 2110 m.s-1, with frequency components lower than 1 MHz, in agreement with numerical results. Investigating guided wave propagation in dental implants should contribute to improved methods for the characterization and stimulation of the IBI.

Reflection of an ultrasonic wave on the bone-implant interface: Comparison of two-dimensional and three-dimensional numerical models.

Quantitative ultrasound is used to characterize osseointegration at the bone-implant interface (BII). However, the interaction between an ultrasonic wave and the implant remains poorly understood. Hériveaux, Nguyen, and Haiat [(2018). J. Acoust. Soc. Am. 144, 488-499] recently employed a two-dimensional (2D) model of a rough BII to investigate the sensitivity of the ultrasonic response to osseointegration. The present letter aimed at assessing the validity of the 2D assumption. The values of the reflection coefficient of the BII obtained with two and three-dimensional models were found not to be significantly different for implant roughness lower than 20 µm. 2D modeling is sufficient to describe the interaction between ultrasound and the BII.

Proliferation of Saos-2 and Ca9-22 cells on grooved and pillared titanium surfaces.

BACKGROUND: Surface nanostructures in titanium (Ti) oral implants are critical for rapid osseointegration. OBJECTIVE: The purpose of this study was to evaluate the growth of osteoblast-like (Saos-2) and epithelial-like (Ca9-22) cells on nanopatterned Ti films. METHODS: Ti films with 500 nm grooves and pillars were fabricated by nanoimprinting, and seeded with Saos-2 and Ca9-22 cells. Cell viability and morphology were assessed by cell proliferation assay and scanning electron microscopy, respectively. RESULTS: As assessed after 1 hour, proliferation of Saos-2 cells was most robust on grooved films than on pillared and smooth films, in this order. These cells approximately doubled on grooved and pillared substrates in 24 hours and after 5 days, but not on smooth surfaces. In contrast, Ca9-22 cells favored smooth surfaces, followed by grooved and pillared films. Indeed, cells sparsely adhered to pillared films over 5 days of incubation (p < 0.05). CONCLUSIONS: The data show that Saos-2 and Ca9-22 cells respond differently to different nanostructures, and highlight the potential use of nanopatterns to promote bone regeneration or to prevent epithelial downgrowth at the implant-bone interface.

Role of implants surface modification in osseointegration: A systematic review.

Long-term and stable fixation of implants is one of the most important points for a successful orthopedic surgery in the field of endoprosthesis. Osseointegration (OI), functional connection between bone and implants, is considered as a pivotal process of cementless implant fixation and integration, respectively. OI is affected by various factors of which the property of implants is of high significance. The modification of implants surface for better OI has raised increasing attention in modern orthopedic medicine. Here, the process of OI and the interactions between implants and ambient bone tissues were emblazed. The knowledge regarding the contemporary surface modification strategies was systematically analyzed and reviewed, including materials used for the fabrication of implants, advanced modification techniques, and key factors in the design of porous implants structure. We discussed the superiority of current surface modification programs and concluded that the problems remain to be solved. The primary intention of this systematic review is to provide comprehensive reference information and an extensive overview for better fabrication and design of orthopedic implants.

Orthopaedic osseointegration: Implantology and future directions.

Osseointegration (OI) is the direct anchorage of a metal implant into bone, allowing for the connection of an external prosthesis to the skeleton. Osseointegration was first discovered in the 1960s based on the microscopic analysis of titanium implant placed into host bone. New bone was observed to attach directly to the metal surface. Following clinical investigations into dentistry applications, OI was adapted to treat extremity amputations. These bone anchored implants, which penetrate the skin and soft tissues, eliminate many of the challenges of conventional prosthetic sockets, such as poor fit and suspension, skin breakdown, and pain. Osseointegrated implants show promise to improve prosthesis use, pain, and function for amputees. The successful process of transcutaneous metal integration into host bone requires three synergistic systems: the host bone, the metal implant, and the skin-implant interface. All three systems must be optimized for successful incorporation and longevity of the implant. Osseointegration begins during surgical implantation of the metal components through a complex interplay of cellular mechanisms. While implants can vary in design-including the original screw, press fit implants, and compressive osseointegration-they face common challenges to successful integration and maintenance of fixation within the host bone. Overcoming these challenges requires the understanding of the complex interactions between each element of OI. This review outlines (a) the basic components of OI, (b) the science behind both the bone-implant and the skin-implant interfaces, (c) the current challenges of OI, and (d) future opportunities within the field.