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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.

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.

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., (© 2024 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.)

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.

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 Mg 2+ , 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., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

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.

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-1β (IL-1β) 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., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

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.

Background: Alumina-titanium (Al 2 O 3 -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 Al 2 O 3 -Ti. Spark plasma sintering (SPS) was used to fabricate Al 2 O 3 -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.

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., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

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.

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., Competing Interests: The authors have declared that no competing interests exist.

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., Competing Interests: AJD is affiliated with DJO Surgical, a commercial company. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products to declare.

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.

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., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

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., (Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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., (© 2019 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals, Inc.)

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.

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.

One of the major causes of implant loosening is due to excessive bone resorption surrounding the implant due to bone remodelling. The objective of the study is to investigate the effects of implant material and implant-bone interface conditions on bone remodelling around tibia bone due to total ankle replacement. Finite element models of intact and implanted ankles were developed using CT scan data sets. Bone remodelling algorithm was used in combination with FE analysis to predict the bone density changes around the ankle joint. Dorsiflexion, neutral, and plantar flexion positions were considered, along with muscle force and ligaments. Implant-bone interfacial conditions were assumed as debonded and bonded to represent non-osseointegration and fully osseointegration at the porous coated surface of the implant. To investigate the effect of implant material, three finite element models having different material combinations of the implant were developed. For model 1, tibial and talar components were made of Co-Cr-Mo, and meniscal bearing was made of UHMWPE. For model 2, tibial and talar components were made of ceramic and meniscal bearing was made of UHMWPE. For model 3, tibial and talar components were made of ceramic and meniscal bearing was made of CFR-PEEK. Changes in implant material showed no significant changes in bone density due to bone remodelling. Therefore, ceramic appears to be a viable alternative to metal and CFR-PEEK can be used in place of UHMWPE. This study also indicates that proper bonding between implant and bone is essential for long-term survival of the prosthetic components.

Titanium micro-scale topography offers excellent osteoconductivity and bone-implant integration. However, the biological effects of sub-micron topography are unknown. We compared osteoblastic phenotypes and in vivo bone and implant integration abilities between titanium surfaces with micro- (1-5 µm) and sub-micro-scale (0.1-0.5 µm) compartmental structures and machined titanium. The calculated average roughness was 12.5 ± 0.65, 123 ± 6.15, and 24 ± 1.2 nm for machined, micro-rough, and sub-micro-rough surfaces, respectively. In culture studies using bone marrow-derived osteoblasts, the micro-rough surface showed the lowest proliferation and fewest cells attaching during the initial stage. Calcium deposition and expression of osteoblastic genes were highest on the sub-micro-rough surface. The bone-implant integration in the Sprague-Dawley male rat femur model was the strongest on the micro-rough surface. Thus, the biological effects of titanium surfaces are not necessarily proportional to the degree of roughness in osteoblastic cultures or in vivo. Sub-micro-rough titanium ameliorates the disadvantage of micro-rough titanium by restoring cell attachment and proliferation. However, bone integration and the ability to retain cells are compromised due to its lower interfacial mechanical locking. This is the first report on sub-micron topography on a titanium surface promoting osteoblast function with minimal osseointegration.

Introduction: High loosening rates after distal femoral replacement may be due to implant design not adapted to specific anatomic and biomechanical conditions., Materials and Methods: A modular tumor system (MUTARS ® , Implantcast GmbH) was implanted with either a curved hexagonal or a straight tapered stems in eight Sawbones ® in two consecutively generated bone defect (10 cm and 20 cm proximal to knee joint level). Implant-bone-interface micromotions were measured to analyze main fixation areas and to characterize the fixation pattern., Results: Although areas of highest relative micromotions were measured distally in all groups, areas and lengths of main fixation differed with respect to stem design and bone defect size. Regardless of these changes, overall micromotions could only be reduced with extending bone defects in case of tapered stems., Conclusions: The tapered design may be favorable in larger defects whereas the hexagonal may be advantageous in defects located more distally.

Purpose: This study aimed to evaluate whether different surface modifications affect the dynamics of bone remodeling at the implant and the adjacent local bone., Materials and Methods: Seventy-two dental implants with different surfaces (smooth and rough control [smCtrl; rCtrl], smooth and rough + O 2 -plasma spray [smPlas; rPlas], smooth and rough + nanocrystalline SiO 2 -hydroxyapatite coating [ncSiO 2 HA] + O 2 -plasma spray [smNB-C; rNB-C]; each n = 12) were bilaterally inserted into the femora of 36 New Zealand white rabbits. Intravital fluorochrome labeling was performed to visualize the dynamics of bone formation. The objectives were quantification of bone-to-implant contact (BIC [%]) at 2 and 4 weeks and the dynamic bone formation (dbf [%]) at the implants' adjacent local bone within 1, 2, and 3 weeks., Results: After 2 weeks, BIC was significantly higher for both smNB-C (BIC: 59% ± 2% SEM) and rNB-C (BIC: 66% ± 3% SEM) compared with controls (BIC: 42% ± 1% SEM; P < .005). After 4 weeks, BIC for rNB-C (65% ± 2%) was superior to all test groups (BIC: 39% ± 2% SEM; P = .012). Regarding dbf (%), neither within 1 (P = .88), 2 (P = .48), nor after 3 weeks (P = .36) did any differences occur among the groups, even in accordance to the implant level., Conclusion: Although distance osteogenesis seems crucial for the development of secondary stability and thus of osseointegration, it apparently does not get affected by a bioactive ncSiO 2 HA surface coating. Changing the surfaces' release kinetics and composition may increase distance osteogenesis.

Polyether-ether-ketone (PEEK) is one of the most common materials used for load-bearing orthopaedic devices due to its radiolucency and favorable mechanical properties. However, current smooth-surfaced PEEK implants can lead to fibrous encapsulation and poor osseointegration. This study compared the in vitro and in vivo bone response to two smooth PEEK alternatives: porous PEEK and plasma-sprayed titanium coatings on PEEK. MC3T3 cells were grown on smooth PEEK, porous PEEK, and Ti-coated PEEK for 14 days and assayed for calcium content, osteocalcin, VEGF and ALP activity. Osseointegration was investigated by implanting cylindrical implants into the proximal tibiae of male Sprague Dawley rats for 8 weeks. Bone-implant interfaces were evaluated using μCT, histology and pullout testing. Cells on porous PEEK surfaces produced more calcium, osteocalcin, and VEGF than smooth PEEK and Ti-coated PEEK groups. Bone ingrowth into porous PEEK surfaces was comparable to previously reported porous materials and correlated well between μCT and histology analysis. Porous PEEK implants exhibited greater pullout force, stiffness and energy-to-failure compared to smooth PEEK and Ti-coated PEEK, despite Ti-coated PEEK exhibiting a high degree of bone-implant contact. These results are attributed to increased mechanical interlocking of bone with the porous PEEK implant surface. Overall, porous PEEK was associated with improved osteogenic differentiation in vitro and greater implant fixation in vivo compared to smooth PEEK and Ti-coated PEEK. These results suggest that not all PEEK implants inherently generate a fibrous response and that topography has a central role in determining implant osseointegration., (Published by Elsevier Ltd.)

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

To investigate the cause of mandibular implant loss, we evaluated the stress distribution in the bone under bite force when the miniimplant was near the root using three-dimensional finite element analysis. Our analysis involved four finite element models with different distances between the implant and adjacent tooth root and three loading conditions. With loading of the tooth only or both the tooth and implant, the peak stress within the bone around the implant neck, displacement, and stress surrounding the bone near the root increased as the distance between the implant and root decreased. However, with separate loading of the implant, the stress did not correlate with the distance between the implant and root. Application of bite force increases stress within bones surrounding mini-implants near the roots of adjacent teeth and may threaten implant stability, but simple orthodontic loading has little effect on the stress distribution at the mini-implant-bone interface.

Bone ongrowth on the surfaces of titanium (Ti)-coated polyetheretherketone (PEEK) materials has been demonstrated in animal models; however, whether this occurs on the surfaces of Ti-coated PEEK cages in lumbar interbody fusion has not been demonstrated clinically in vivo. This prospective observational study was aimed to develop and validate a computed tomography (CT) color mapping based on Hounsfield unit (HU) values for evaluation of bone ongrowth on the surfaces of the Ti-coated PEEK cage after posterior lumbar interbody fusion (PLIF).Twenty-four consecutive patients (11 men and 13 women; mean age, 67.0 years; range, 20-82 years) who underwent single- or 2-level PLIF since March 2015 were included. Two Ti-coated PEEK cages were inserted in all PLIF segments. From reconstructed sagittal planes from postoperative CT scans (within 1 week and 6 months postoperatively), bone ongrowth on the surfaces of cage frames was evaluated by CT color mapping. Inter- and intraobserver reliability of the assessment of bone ongrowth by CT color mapping was evaluated by Cohen's kappa coefficient. The relation between CT color mapping and HU values on the surfaces of cage frames was also analyzed.A total of 248 surfaces of cage frames were evaluated. Bone ongrowth was observed in 134 of 248 surfaces (54.0%) by CT color mapping. Intraobserver reliability for the evaluation of bone ongrowth was kappa = 0.831, and interobserver reliability was kappa = 0.713. The HU values in the local regions of interest (ROIs) on the surfaces of cage frames where the postoperative bone ongrowth existed on CT color mapping increased significantly postoperatively (P < .001), and the median postoperative change rate of the HU values in the local ROIs was 22.4%.The assessment of bone ongrowth on the surfaces of Ti-coated PEEK cages by CT color mapping had adequate inter- and intraobserver reliability, which was useful especially in detecting local increase in HU values on the surfaces of the cages. This method is an easy and visually comprehensible method for the assessment of bone ongrowth in the bone-implant interface.

Objectives: This study aimed to compare the molecular events in implant-adherent cells and in peri-implant bone during the osseointegration of machined and oxidized titanium implants in smokers and nonsmokers., Materials and Methods: Twenty-four smokers and 24 nonsmokers each received machined and anodically oxidized mini-implants. The mini-implants and the surrounding bone were retrieved after 1, 7, and 28 days, for gene expression analysis of selected factors using quantitative polymerase chain reaction (qPCR)., Results: Differences between machined and oxidized implants were more evident in the implant-adherent cells than the peri-implant bone. The machined implants revealed higher expression of proinflammatory cytokines, interleukin-8 (IL-8) (in nonsmokers), and tumor necrosis factor-alpha (in nonsmokers and smokers), compared with the oxidized implants. Conversely, the expression of bone formation genes, alkaline phosphatase and osteocalcin, was generally higher at the oxidized implants. In smokers, the temporal pattern revealed the delayed and initial inhibition of osteoblastic and osteoclastic gene expression, respectively, mainly at the machined implants. In contrast, oxidized implants revealed higher expression of bone remodeling, cathepsin K (CatK) and calcitonin receptor, and coupling, receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin, genes after 7 day in smokers., Conclusions: The implant-adherent cells are more sensitive to surface properties and smoking conditions than the cells in the peri-implant bone. Smoking imposes inhibitory effects on the initial molecular events of osseointegration in the human bone-implant interface. The surface properties of oxidized implants appear to have a beneficial effect on osseointegration by mitigating the smoking-induced negative effects., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The aim of this study was to gain insights into the biology and mechanics of immediate postextraction implant osseointegration. To mimic clinical practice, murine first molar extraction was followed by osteotomy site preparation, specifically in the palatal root socket. The osteotomy was positioned such that it removed periodontal ligament (PDL) only on the palatal aspect of the socket, leaving the buccal aspect undisturbed. This strategy created 2 distinct peri-implant environments: on the palatal aspect, the implant was in direct contact with bone, while on the buccal aspect, a PDL-filled gap existed between the implant and bone. Finite element modeling showed high strains on the palatal aspect, where bone was compressed by the implant. Osteocyte death and bone resorption predominated on the palatal aspect, leading to the loss of peri-implant bone. On the buccal aspect, where finite element modeling revealed low strains, there was minimal osteocyte death and robust peri-implant bone formation. Initially, the buccal aspect was filled with PDL remnants, which we found directly provided Wnt-responsive cells that were responsible for new bone formation and osseointegration. On the palatal aspect, which was devoid of PDL and Wnt-responsive cells, adding exogenous liposomal WNT3A created an osteogenic environment for rapid peri-implant bone formation. Thus, we conclude that low strain and high Wnt signaling favor osseointegration of immediate postextraction implants. The PDL harbors Wnt-responsive cells that are inherently osteogenic, and if the PDL tissue is healthy, it is reasonable to preserve this tissue during immediate implant placement.

In lamellar bone, a network of highly oriented interconnected osteocytes is organized in concentric layers. Through their cellular processes contained within canaliculi, osteocytes are highly mechanosensitive and locally modulate bone remodeling. We review the recent developments demonstrating the significance of the osteocyte lacuno-canalicular network in bone maintenance around implant biomaterials. Drilling during implant site preparation triggers osteocyte apoptosis, the magnitude of which correlates with drilling speed and heat generation, resulting in extensive remodeling and delayed healing. In peri-implant bone, osteocytes physically communicate with implant surfaces via canaliculi and are responsive to mechanical loading, leading to changes in osteocyte numbers and morphology. Certain implant design features allow peri-implant osteocytes to retain a less aged phenotype, despite highly advanced extracellular matrix maturation. Physicochemical properties of anodically oxidized surfaces stimulate bone formation and remodeling by regulating the expression of RANKL (receptor activator of nuclear factor-κB ligand), RANK, and OPG (osteoprotegerin) from implant-adherent cells. Modulation of certain osteocyte-related molecular signaling mechanisms (e.g., sclerostin blockade) may enhance the biomechanical anchorage of implants. Evaluation of the peri-implant osteocyte lacuno-canalicular network should therefore be a necessary component in future investigations of osseointegration to more completely characterize the biological response to materials for load-bearing applications in dentistry and orthopedics.

Objective: To evaluate whether hyperbaric oxygen (HBO) treatment has a favorable effect on implant osseointegration in diabetic rabbits., Material and Methods: An experimental diabetes model was induced in 32 New Zealand rabbits through IV injection of alloxan. After the state of diabetes had been confirmed, one dental implant was placed in the metaphysical region of each animal's tibia. After the implants' placements, the animals were divided into two groups. Half of the animals underwent HBO treatment, while the other group did not receive HBO treatment and served as the control group. The animals were euthanized at the 4th and 8th weeks. The osseointegration of the implants were compared by histomorphometry and resonance frequency analysis (RFA)., Results: The Bone Implant Contact (BIC) values were significantly higher in the HBO group than in the control group at the 4th week. There was no difference in the BIC values between the groups at the 8th week. There was no significant difference in the RFA scores between the groups both at the 4th and 8th weeks after the operation., Conclusion: Histomorphometry findings suggest that HBO has positive effect on implant osseointegration in the early healing period in diabetic rabbits. However, implant stability is not affected by HBO treatment.

Purpose: Recently, a torque-measuring micromotor that calculates the integral (I) of torque-depth curve at implant insertion was developed. This device was used to investigate the correlation between (I) and mechanical stress in photoelastic resin blocks with the density of D1 bone., Materials and Methods: Using the micromotor, 40 implants (3.75 × 12 mm) were placed in 40 D1 blocks that had been prepared in four different ways. Four groups of 10 blocks each were prepared according to tunnel length (12 or 14 mm) and debris removal (yes or no). After insertion, peri-implant mechanical stress and its correlation with (I) were assessed by photoelastic and linear regression analysis, respectively. Analysis of variance (ANOVA) and Kruskal-Wallis tests investigated differences in mechanical stress patterns and dynamic parameters among the groups., Results: (I) significantly correlated with mechanical stress in D1 resin under all conditions, except for 12-mm implant sites still containing debris. The correlation was significant concerning the whole dataset (r = 0.979) and separately for the coronal (r = 0.940), middle (r = 0.964), and apical (r = 0.948) portions of the implants. Peak torque did not correlate significantly with peri-implant mechanical stress. Longer implant sites and debris removal were significantly associated with lower peri-implant mechanical stress., Conclusion: (I) provides a reliable measure of mechanical stress in D1 bone during implant placement. Preparation of longer osteotomies and routine removal of all debris might reduce peri-implant bone stress significantly.

Introduction: Despite the successful clinical application of titanium (Ti) as a biomaterial, the exact cellular and molecular mechanisms responsible for Ti osseointegration remains unclear, especially because of the limited methodological tools available in this field., Objective: In this study, we present a microscopic and molecular characterization of an oral implant osseointegration model using C57Bl/6 mice., Material and Methods: Forty-eight male wild-type mice received a Ti implant on the edentulous alveolar crest and the peri-implant sites were evaluated through microscopic (μCT, histological and birefringence) and molecular (RealTimePCRarray) analysis in different points in time after surgery (3, 7, 14 and 21 days)., Results: The early stages of osseointegration were marked by an increased expression of growth factors and MSC markers. Subsequently, a provisional granulation tissue was formed, with high expression of VEGFb and earlier osteogenic markers (BMPs, ALP and Runx2). The immune/inflammatory phase was evidenced by an increased density of inflammatory cells, and high expression of cytokines (TNF, IL6, IL1) chemokines (CXCL3, CCL2, CCL5 and CXC3CL1) and chemokine receptors (CCR2 and CCR5). Also, iNOS expression remained low, while ARG1 was upregulated, indicating predominance of a M2-type response. At later points in time, the bone matrix density and volume were increased, in agreement with a high expression of Col1a1 and Col21a2. The remodelling process was marked by peaks of MMPs, RANKL and OPG expression at 14 days, and an increased density of osteoclasts. At 21 days, intimate Ti/bone contact was observed, with expression of final osteoblast differentiation markers (PHEX, SOST), as well as red spectrum collagen fibers., Conclusions: This study demonstrated a unique molecular view of oral osseointegration kinetics in C57Bl/6 mice, evidencing potential elements responsible for orchestrating cell migration, proliferation, ECM deposition and maturation, angiogenesis, bone formation and remodeling at the bone-implant interface in parallel with a novel microscopic analysis.

Osseointegrated implants are frequently used in reconstructive surgery, both in the dental and orthopedic field, restoring physical function and improving the quality of life for the patients. The bone anchorage is typically evaluated at micrometer resolution, while bone tissue is a dynamic composite material composed of nanoscale collagen fibrils and apatite crystals, with defined hierarchical levels at different length scales. In order to understand the bone formation and the ultrastructure of the interfacial tissue, analytical strategies needs to be implemented enabling multiscale and multimodal analyses of the intact interface. This paper describes a sample preparation route for successive analyses allowing assessment of the different hierarchical levels of interest, going from macro to nano scale and could be implemented on single samples. Examples of resulting analyses of different techniques on one type of implant surface is given, with emphasis on correlating the length scale between the different techniques. The bone-implant interface shows an intimate contact between mineralized collagen bundles and the outermost surface of the oxide layer, while bone mineral is found in the nanoscale surface features creating a functionally graded interface. Osteocytes exhibit a direct contact with the implant surface via canaliculi that house their dendritic processes. Blood vessels are frequently found in close proximity to the implant surface either within the mineralized bone matrix or at regions of remodeling.

Background: Titanium (Ti) implants are extensively used in reconstructive surgery and orthopedics. However, the intrinsic inertness of untreated Ti implants usually results in insufficient osseointegration. In order to improve the osteoconductivity properties of the implants, they are coated with hierarchical microtopographic/nanotopographic coatings employing the method of molecular layering of atomic layer deposition (ML-ALD)., Results: The analysis of the fabricated nanostructured relief employing scanning electron microscopy, atomic force microscopy, and electron spectroscopy for chemical analysis clearly demonstrated the formation of the nanotopographic (<100 nm) and microtopographic (0.1-0.5 μm) titano-organic structures on the surface of the nanograined Ti implants. Subsequent coincubation of the MC3T3-E1 mouse osteoblasts on the microtopographic/nanotopographic surface of the implants resulted in enhanced osteogenic cell differentiation (the production of alkaline phosphatase, osteopontin, and osteocalcin). In vivo assessment of the osseointegrative properties of the microtopographically/nanotopographically coated implants in a model of below-knee amputation in New Zealand rabbits demonstrated enhanced new bone formation in the zone of the bone-implant contact (as measured by X-ray study) and increased osseointegration strength (removal torque measurements)., Conclusion: The fabrication of the hierarchical microtopographic/nanotopographic coatings on the nanograined Ti implants significantly improves the osseointegrative properties of the intraosseous Ti implants. This effect could be employed in both translational and clinical studies in orthopedic and reconstructive surgery., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: Studies have shown that strontium-doped medical applications benefit bone metabolism leading to improved bone healing and osseointegration. Based on this knowledge, the aim of the study was to evaluate the performance of an implant surface, functionalized by a physical vapor deposition (PVD) coating (Ti-Sr-O), designed to yield predictable release of strontium. The Ti-Sr-O functionalized surface is compared to a routinely used, commercially available surface (SLActive™) with respect to bone-to-implant contact (BIC%) and new bone formation (BF%) in two defined regions of interest (ROI-I and ROI-II, respectively)., Materials and Methods: Ti-Sr-O functionalized, SLActive, and Grade 4 titanium implants were inserted in the femoral condyle of adult male New Zealand White rabbits. The PVD magnetron-sputtered Ti-Sr-O surface coating was characterized using scanning electron microscopy (SEM) for morphology and coating thickness. Strontium release and mechanical stability of the coating, under simulated insertion conditions, were evaluated. Furthermore, histomorphometrical BIC and BF were carried out 2 weeks after insertion., Results: Histomorphometry revealed increased bone formation of Ti-Sr-O with significant differences compared to SLActive and Grade 4 titanium in both regions of interest, ROI-I and ROI-II, at 0-250 µm and 250-500 µm distance from the implant surfaces. Analogous results of bone-to-implant contact were observed for the two modified surfaces., Conclusion: The results show that a nanopatterned Ti-Sr-O functionalized titanium surface, with sustained release of strontium, increases peri-implant bone volume and could potentially contribute to enhancement of bone anchorage of osseointegrated implants., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Osseointegration of load-bearing orthopaedic implants, including interbody fusion devices, is critical to long-term biomechanical functionality. Mechanical loads are a key regulator of bone tissue remodeling and maintenance, and stress-shielding due to metal orthopaedic implants being much stiffer than bone has been implicated in clinical observations of long-term bone loss in tissue adjacent to implants. Porous features that accommodate bone ingrowth have improved implant fixation in the short term, but long-term retrieval studies have sometimes demonstrated limited, superficial ingrowth into the pore layer of metal implants and aseptic loosening remains a problem for a subset of patients. Polyether-ether-ketone (PEEK) is a widely used orthopaedic material with an elastic modulus more similar to bone than metals, and a manufacturing process to form porous PEEK was recently developed to allow bone ingrowth while preserving strength for load-bearing applications. To investigate the biomechanical implications of porous PEEK compared to porous metals, we analyzed finite element (FE) models of the pore structure-bone interface using two clinically available implants with high (> 60%) porosity, one being constructed from PEEK and the other from electron beam 3D-printed titanium (Ti). The objective of this study was to investigate how porous PEEK and porous Ti mechanical properties affect load sharing with bone within the porous architectures over time. Porous PEEK substantially increased the load share transferred to ingrown bone compared to porous Ti under compression (i.e. at 4 weeks: PEEK = 66%; Ti = 13%), tension (PEEK = 71%; Ti = 12%), and shear (PEEK = 68%; Ti = 9%) at all time points of simulated bone ingrowth. Applying PEEK mechanical properties to the Ti implant geometry and vice versa demonstrated that the observed increases in load sharing with PEEK were primarily due to differences in intrinsic elastic modulus and not pore architecture (i.e. 4 weeks, compression: PEEK material/Ti geometry = 53%; Ti material/PEEK geometry = 12%). Additionally, local tissue energy effective strains on bone tissue adjacent to the implant under spinal load magnitudes were over two-fold higher with porous PEEK than porous Ti (i.e. 4 weeks, compression: PEEK = 784 ± 351 microstrain; Ti = 180 ± 300 microstrain; and 12 weeks, compression: PEEK = 298 ± 88 microstrain; Ti = 121 ± 49 microstrain). The higher local strains on bone tissue in the PEEK pore structure were below previously established thresholds for bone damage but in the range necessary for physiological bone maintenance and adaptation. Placing these strain magnitudes in the context of literature on bone adaptation to mechanical loads, this study suggests that porous PEEK structures may provide a more favorable mechanical environment for bone formation and maintenance under spinal load magnitudes than currently available porous 3D-printed Ti, regardless of the level of bone ingrowth., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: The objective of this study was to assess, by histomorphometric analysis, the degree of bone apposition on two types of dental implant's surfaces: a novel implant that combines Al 2 O 3 abrasive particle blasting with thermochemical treatment (ContacTi), compared to a standard surface treatment obtained by sandblasting and acid etching (shot blasting)., Materials and Methods: Twelve minipigs were used, placing the studied implants in the maxillae, and divided into three groups according to the time of sacrifice: 2, 4, and 8 weeks after implant placement. Histological and histomorphometric analyses were performed following standardized tissue polymerization, cutting, and staining and examined under optical and high-resolution electron microscope., Results: For all measurements, the novel surface presented higher levels of osseointegration as compared to the shot blasting surface. Bone to implant contact (BIC) in the maxillae for ContacTi presented values of 49.02, 83.20, and 85.58% at 2, 4, and 8 weeks, respectively, significantly higher compared to the shot blasting surface values of 39.32, 46.53, and 46.20% for the same time points. Bone area density (BAD) presented values of 26.52, 61.21, and 59.50% for ContacTi surface implants and 22.95, 36.26, and 49.50% for the shot blasted surface implants. Signs of osteoconductivity were observed in the ContacTi surfaces at 2 weeks., Conclusions: The ContacTi surface achieved a faster growth of hard tissues around the implants, when compared to the shot blasting surface, and for all evaluated histomorphometric parameters, the values were higher at all measured time points., Clinical Relevance: ContacTi could be a new surface improving the osseointegration in oral implantology.

Introduction: Traditional prosthetic solutions expose the amputee to numerous problems that limit his ability to safely perform the normal activities of daily life. In order to eliminate the problems related to the use of the traditional prosthesis with socket, a new technique was developed for fixing the prosthesis to the amputees based on the principle of osseointegration. The aim of this paper is to study and analyze the stress distribution on the interface between a trans-humeral osseointegrated prosthetic implant and the residual bone, identifying the most stressed areas and thus foreseeing possible failure phenomena of the entire prosthetic system and, after, to compare the stress distribution on three different prosthetic designs that differ from each other for some geometric characteristics., Materials and Methods: A healthy individual mimics two fall scenarios of which the trans-humeral amputees can most likely be victims: Static fall and Dynamic fall. A force platform (P-6000, BTS Bioengineering) is required for load data acquisition. The CAD model of the trans-humeral osseointegrated implant was created following the guidelines of the OPRA implant. The bone model was created starting from the CAT scan of a left humerus. The FEM simulation was conducted throught a linear analysis., Results: Both during static fall and dynamic fall, similar trends have been observed for the reaction force Fz, the torque moment Tz, the bending moments Mx and My. From the analysis of the von Mises stress distribution it was found that the stress distribution is more homogeneous in the case where the thread of the fixture is made by a triangular profile with height of the thread equal to 0.5 mm. However, it can be seen that, when passing from a thread with height of 0.5 mm to a 1 mm, there is a slight decrease in the stress on the whole contact zone between the fixture and the humerus. The same improvement can also be seen in the case of trapezoidal threading., Conclusion: By modifying the height and/or by varying the thread profile, are obtained slightly better results with respect to the case with a 0.5 mm height triangular thread., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Microarc oxidation (MAO) has become a promising technique for the surface modification of implants. Therefore, the aims of this study were to further quantitatively and qualitatively evaluate the osteointegration abilities of MAO-treated and smooth surface (SF) implants in vivo and to investigate the areas in which the superiority of MAO-treated implants are displayed. In a rabbit model, a comprehensive histomorphological, osteogenic, mineralizational, and integrative assessment was performed using light microscopy, fluorescence microscopy, confocal laser scanning microscopy, and radiographic analyses. Compared with the SF groups, the MAO-treated groups exhibited more active contact osteogenesis, as well as distant osteogenesis, under fluorescence examination, the mineral apposition rate was found to be greater for all of the MAO-treated implants, and the osteointegration index (OI) value was greater in the MAO-treated groups at different times. In conclusion, the calcium-rich amorphous layer created by MAO provided a better environment for osteointegration, with more active contact osteogenesis, a more rapid mineral apposition rate and greater OI values.

Objective: To assess the influence of implant thread shape and inclination on the mechanical behaviour of bone-implant systems. The study assesses which factors influence the initial and full osseointegration stages., Methods: Point clouds of the original implant were created using a non-contact reverse engineering technique. A 3D tessellated surface was created using Geomagic Studio ® software. From cross-section curves, generated by intersecting the tessellated model and cutting-planes, a 3D parametric CAD model was created using SolidWorks ® 2017. By the permutation of three thread shapes (rectangular, 30° trapezoidal, 45° trapezoidal) and three thread inclinations (0°, 3° or 6°), nine geometric configurations were obtained. Two different osseointegration stages were analysed: the initial osseointegration and a full osseointegration. In total, 18 different FE models were analysed and two load conditions were applied to each model. The mechanical behaviour of the models was analysed by Finite Element (FE) Analysis using ANSYS ® v. 17.0. Static linear analyses were also carried out., Results: ANOVA was used to assess the influence of each factor. Models with a rectangular thread and 6° inclination provided the best results and reduced displacement in the initial osseointegration stages up to 4.58%. This configuration also reduced equivalent VM stress peaks up to 54%. The same effect was confirmed for the full osseointegration stage, where 6° inclination reduced stress peaks by up to 62%., Significance: The FE analysis confirmed the beneficial effect of thread inclination, reducing the displacement in immediate post-operative conditions and equivalent VM stress peaks. Thread shape does not significantly influence the mechanical behaviour of bone-implant systems but contributes to reducing stress peaks in the trabecular bone in both the initial and full osseointegration stages., (Copyright © 2018 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.)

Tissue engineering has been emerging as a valid approach to the current therapies for bone regeneration/substitution. Tissue-engineered bone constructs have the potential to alleviate the demand arising from the shortage of suitable autograft and allograft materials for augmenting bone healing. Scaffolds play a central role in tissue engineering research, they not only provide as structural support for specific cells but also provide as the templates to guide new tissue growth and construction. In this survey we describe application of graphene based nano-biomaterials for bone tissue engineering. In this article, application of different graphene based materials on construction of manufacture scaffolds for bone tissue engineering was discussed. It begins by giving the reader a brief background on tissue engineering, followed by a comprehensive description of all the relevant components of graphene based materials, going from materials to scaffolds and from cells to tissue engineering strategies that will lead to "engineered" bone. In this survey, more recent studies on the effects of graphene on surface modifications of scaffold materials was discused. The ability of graphene to improve the biological properties of scaffold materials, and its ability to promote the adhesion, proliferation, and osteoblasts have been demonstrated in several studies which we discuss in this survey article. We further highlight how the properties of graphene are being exploited for scaffolds in bone tissue engineering, comprehensively surveying recent experimental works featuring graphene and graphene derivatives. Bone tissue engineering, for the purpose of this survey, is the use of a scaffolding material to either induce formation of bone from the surrounding tissue or to act as a carrier or template for implanted bone cells or other agents. Materials used as bone tissue-engineered scaffolds may be injectable or rigid, the latter requiring an operative implantation procedure.

Purpose: This study evaluated the effect of drilling speed on early bone healing in the mandible of dogs., Material and Methods: Six dogs were selected, and mandibular premolars and molars were extracted. After 2 months, 3 hydroxyapatite-surfaced fixtures were implanted with drilling speeds of 50, 800, and 1200 rpm on the right side first and then on the left side after 2 weeks. Implant stability quotient (ISQ) was measured on insertion, after 2 and 4 weeks., Results: Based on the ISQ measurement, the 1200-rpm group showed a higher value than the 50-rpm group at 2 weeks and 4 weeks (P < 0.05). New bone formation around the implant was highest for the 800-rpm group at 2 weeks and the 1200-rpm group at 4 weeks. The bone-implant contact of the superior half of the alveolar bone was highest for the 800-rpm group at 2 weeks and the 1200-rpm group at 4 weeks. There was no statistically significant difference., Conclusion: This study suggests that 50, 800, and 1200 rpm are drilling speeds which can expect favorable outcome, yet, higher drilling speed presented overall the best biological responses.

Purpose: To evaluate if an inorganic graft applied before implant insertion interferes with osseointegration., Materials and Methods: The bilateral mandibular incisors of 12 rabbits were extracted. One of the sockets was randomly filled with an inorganic xenogenic bone graft, whereas the remaining socket was allowed to heal naturally and served as a control. After 60 days, titanium implants were inserted into healing areas. The animals were killed 60 days after. Bone depositions were marked with fluorochrome oxytetracycline, alizarin, and calcein and evaluated using confocal laser scanning microscopy. Bone-to-implant contact (BIC) and bone area (BA) within the limits of the implant threads were analyzed. Data were compared statically by paired t tests, one-way ANOVA, and Bonferroni post hoc tests (α = 0.05)., Results: No differences between the control and experimental groups in bone deposition for each marker, in either the BIC or BA analysis were observed. The bone deposition marked by alizarin (14-21 days) was the highest, followed by oxytetracycline (0 and 7 days) and calcein (45 and 52 days) in both groups (P < 0.05)., Conclusion: The bone healing or the course of osseointegration was not impaired by the use of an inorganic xenogenic graft before insertion of a titanium implant.

Purpose: Implant failure is a frequent complication in corrective surgery for early onset scoliosis, since considerable forces are acting on small and fragile vertebrae. Osseointegration showing biomechanical and histological improvement in bone-implant interface (BII) after dental implant placement has been well investigated. However, there are no studies regarding osseointegration in immature vertebral bone. The purpose was to evaluate the timecourse of biomechanical and histological changes at BII after pedicle screw placement using in vivo immature porcine model., Methods: Ten immature porcine were instrumented with titanium pedicle screws in the thoracic spine. After a 0-, 2-, 4-, and 6-month survival periods, the spines were harvested at the age of 12 months. Histological evaluation of BII was conducted by bone volume/tissue volume (BV/TV) and bone surface/implant surface (BS/IS) measurements. Bone mineral density (BMD) measurement and biomechanical testing of BII were done., Results: Contact surface and bone volume around the screw threads were significantly increased over the time. BV/TV and BS/IS were improved with statistically significant differences between 0- and ≥4-month (p ≤ 0.001) periods. BMD in all subjects was determined to be the same (p ≥ 0.350). Pullout strength was also increased over time with significant differences between 0- and ≥2-month (p ≤ 0.011) periods., Conclusion: Improved stability at BII caused by osseointegration was confirmed by in vivo immature porcine model. A two-stage operation is proposed based on the osseointegration theory, in which an implant is installed in advance in the vertebrae at the first stage and deformity correction surgery is performed after sufficient stability is obtained by osseointegration at a later stage.

Introduction: Clinical research has documented that cage subsidence and the loss of balance correction is a significant complication related to spinal fusion. Subsidence is a multifactorial complication, where implant design is one important element. The aim of the study is to compare the rigidity and bone-implant relative motion of segments treated with either a conventional one-piece ALIF cage versus a two-piece ALIF cage, which adapts in situ and permits 7°-21° of lordosis., Methods: Seven lumbosacral (L3-S1) human cadaver specimens were tested in a universal spine tester in the intact condition, the specimens instrumented with a two-piece ALIF cage (Statur ® -L, FBC Device, Denmark) and a one-piece ALIF cage (Pezo™-A, Ulrich GmbH & Co. KG., Germany), both supplemented with a pedicle screw system using pure moments of ±7.5 Nm in three principal motion directions. For assessment of the bone-implant interface, fluoroscopic videos were captured during motion and 3D motion was measured using an optical motion capturing system., Results: Significantly less motion at the implant-endplate interface was found for the two-piece cage (1.0° ± 0.6°) in comparison to the one-piece cage (4.2° ± 1.7°) in flexion/extension. No significant differences in segment rigidity were found between the one-piece and two-piece cages in the 360° setup, while both configurations significantly reduced the range of motion compared to the intact condition (p < 0.05)., Conclusion: In comparison to the traditional one-piece ALIF cages, the two-piece cage concept reduced the relative motion at the bone-implant interface without compromising stability.

Percutaneous osseointegrated (OI) prostheses directly connect an artificial limb to the residual appendicular skeleton via a permanently implanted endoprosthesis with a bridging connector that protrudes through the skin. The resulting stoma produces unique medical and biological challenges. Previously, a study using a large animal amputation model indicated that infection could be largely prevented, for at least a 12-month period, but the terminal epithelium continued to downgrow. The current study was undertaken to test the longer-term efficacy of this implant construct to maintain a stable skin-implant interface for 24 months. Using the previously successful amputation and implantation surgical procedure, a total of eight sheep were fitted with a percutaneous OI prosthesis. Two animals were removed from the study due to early complications. Of the remaining six sheep, one (16.7%) became infected at 15-months post-implantation and five remained infection-free for the intended 24 months. The histological data of the remaining animals further confirmed the grossly observable epithelial downgrowth. Albeit a receding interface, it was clear that all animals that survived to the end of the study had residual fibrous soft-tissue ingrowth into, and debris within, the exposed titanium porous-coated surface. Overall, the data demonstrated that the porous coated subdermal barrier offered initial protection against infection. However, the fibrous skin attachment was continuously lysed over time by the down-growing epithelium.

Objective: To evaluate the effects of metformin on bone healing around titanium implants inserted in non-diabetic rats., Methods: Twenty Wistar rats were randomly assigned to one of the following groups: control group (n = 10): rats without metformin treatment; MT group (n = 10): rats treated with metformin (40 mg/kg/day by gavage). At thirty days after implant placement, animals were euthanized. Histometric measurements of bone-to-implant contact (BIC) and bone area (BA), in addition to immunohistochemical analysis of the number of cells stained for RANKL and OPG, were assessed in the cortical and medullary areas around implants., Results: The percentages of BIC and BA in the cortical bone were significantly lower in the MT group than in the control group (P < 0.05). Furthermore, the medullary bone around the implants inserted in the metformin-treated animals exhibited an increased number of RANKL-stained cells than that around the implants inserted in the control animals (P < 0.05)., Conclusions: Metformin negatively affected osseointegration by reducing the percentages of BIC and BA and increasing the expression of RANKL around titanium implants inserted in non-diabetic rats., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: This randomized clinical trial analyzed crestal bone changes and soft tissue dimensions surrounding implants with an internal tapered connection placed in the mandible anterior region at different depths (equicrestal and subcrestal)., Materials and Methods: Eleven edentulous patients (five implants per patient) were randomly divided in a split-mouth design: G1, 28 equicrestal implants; and G2, 27 subcrestal implants. All implants were immediately loaded. Correlation between keratinized tissue width (KTW) and vertical mucosa thickness (MT) with soft tissue recession was analyzed. Intraoral radiographs were used to evaluate crestal bone changes. Patients were assessed immediately, 4-, and 8-months after implant placement. Rank-based ANOVA-type statistical test was used for comparison between groups (α = 0.05)., Results: Fifty-five implants (G1 = 28 and G2 = 27) were assessed in 11 patients. Implant survival rate was 100% for both groups. Both tested implant placement depths presented similar crestal bone loss (P > 0.05). Significant crestal bone loss for each group was found in the different measurement times (T4 and T8) (P < 0.05). Implant placement depths, KTW, and vertical MT had no effect on soft tissue recession (P > 0.05)., Conclusions: Different implant placement depths do not influence crestal bone changes. Soft tissue behavior is not influenced by different implant placement depths or by the amount of keratinized tissue., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)