Bone-implant Osseointegration Research Articles

Design and Analysis of Composite Biomaterial Bone Graft Plate

The mixing technique was applied in this study to enhance the strength performance of the cement. The addition of 3% by weight of hydroxyapatite (HA) nanoparticles were mixed with 97% polymethyl methacrylate (PMMA) acrylic polymer, which has a nano size to serve as the matrix material. The surface roughness and continuous porosity of the bone cement were found to be slightly increased by the incorporation of nanoparticles, which enhanced bone-implant osseointegration and ingrowth. Atomic force microscopy (AFM) analysis revealed that the addition of hydroxyapatite (HAp) nanoparticles resulted in a surface roughness value (Sa) of 16.25 nm, which is similar to that of natural bone. The energy-dispersive X-ray spectroscopy (EDS) mapping results discover precentor material and uniform distribution. The Sample exhibited promising results in the antibacterial test, showing efficacy against bacteria both with and without sterilization, confirming its antibacterial properties. The mechanical tests conducted on the sample, including tensile, compression, bending and Vickers hardness tests, yielded favorable results and indicated that the sample is suitable for its intended application. In the theoretical works the design of the bone, screw, and bone plate was conducted using SolidWorks, followed by an analysis using ANSYS under both axial and bending load conditions. The theoretical analysis revealed that the safety factor was less than 1 when an axial load of 13 N was applied and a bending load of 2 N was applied, indicating that the structure may not be able to withstand these loads safely. Under both ambient and physiologically relevant conditions in the human body, HA and PMMA have demonstrated to be excellent choices for enhancing the clinical performance of bone cement. This, in turn, can lead to increased longevity of implants, decreased patient risk, and lower healthcare costs

The Biomechanical Investigation of Osseointegration Levels in Titanium Implants Simultaniously Placed with Different Bone Grafts.

Dental implant-supported prostheses have been scientifically accepted and have been a common treatment choice in the case reconstructing of partial or total tooth loss. In additon, bone grafts (alloplast, xsenograft, allograft) are frequently used in implant and sinus lift surgical procedures. The aim of this study is to investigate the bone-implant osseointegration levels of titanium implants simultaniously placed with different bone grafts. In the study, 32 female S. Dawley rats were divided into four groups. In the control group (n = 8), turned surface implants with a 2.5 mm diameter and a 4 mm length were placed in the tibia of the rats without the use of a graft material. In the experimental groups, bone cavities were opened in the tibias of the rats and a synthetic (alloplast) graft (n = 8), human allograft (n = 8), and bovine xsenograft (n = 8) were placed simultaniously with a 2.5 mm diameter and a 4 mm length turned surface titanium implants. The cavities in the experimental groups were opened with a 4 mm diameter and a 5 mm length. After 8 weeks of recovery, all rats were sacrificed at the end of the experimental period. The implants and surrounding bone tissue were removed. The removed tissue was subjected to biomechanical analysis in order to evaluate bone-implant osseointegration and peri-implant new bone formation. The Kolmogorov-Smirnov test, Kruskal-Wallis test, and Mann-Whitney U-test were used in the study. Significance was evaluated at the P < 0.05 level. In the biomechanical analyses, it was determined that there was no statistically significant difference between the control group and the other three groups in which different graft materials were applied in terms of bone-implant osseointegration (P > 0.05). In other words, in the biomechanical analyses, no statistical difference was found between any of the groups. As a result of this study, it can be thought that different graft materials can be successfully used in peri-implant-guided bone regeneration and may be an alternative to autogenous grafts.

2D silicene nanosheets-loaded coating for combating implant-associated infection

Implant-associated infection (IAI) is an unsolved problem in orthopaedics. Current therapies, including antibiotics and surgical debridement, can lead severe clinical and financial burdens on patients. Therefore, there is an urgent need to reinforce the inherent antibacterial properties of implants. Recently, two-dimensional (2D) silicene nanosheets (SNs) have gained increasing attention in biomedical fields owing to their considerable biocompatibility, biodegradability and strong photothermal-conversion performance. Herein, a dual-functional photosensitive coating on a Ti substrate (denoted as TPSNs) was rationally fabricated for bacterial inhibition and osteogenesis promotion. For the first time, SNs were loaded onto the surface of implants. Hyperthermia generated by the SNs and polydopamine (PDA) coating under 808 nm laser irradiation achieved the in vitro anti-bacterial efficiency of 90.7 ± 2.4 % for S. aureus and 88.0 ± 5.8 % for E. coli, respectively. In addition, TPSNs exhibited promising biocompatibility for the promotion of BMSC (bone marrow mesenchymal stem cells) proliferation and spreading. The presence of silicon (Si) in TPSNs contributed to the improved osteogenic differentiation of BMSCs, elevating the expressions of RUNX2 and OCN. In animal experiments, the combination of TPSNs with photothermal therapy (PTT) achieved an anti-bacterial efficiency of 89.2 % ± 1.6 % against S. aureus. Furthermore, TPSNs significantly improved bone-implant osseointegration in vivo. Overall, the development of a dual-functional TPSNs coating provides a new strategy for combating IAI.

Combined photothermal and sonodynamic therapy using a 2D black phosphorus nanosheets loaded coating for efficient bacterial inhibition and bone-implant integration

Surgical site infection (SSI) remains a major threat for implant failure in orthopedics. Herein, we report a dual-functional coating on Ti implants (named Ti/PDA/BP) with the integration of two-dimensional (2D) photo-sono sensitive black phosphorus nanosheets (BPNSs) and polydopamine (PDA) for efficient bacterial inhibition and bone-implant integration. For the first time, we employ BPNSs as generators of reactive radicals (ROS) under ultrasound (US) stimuli for implant associated infection. Additionally, the application of PDA improves the stability of BPNSs, the biocompatibility and photothermal performance of this hybrid coating. The as-prepared Ti/PDA/BP coating exhibits superior biocompatibility, bioactivity, photothermal and sonodynamic conversion abilities. Owing to the synergistic effect of hyperthermia and ·OH, Ti/PDA/BP damages the membrane and antioxidant system of Staphylococcus aureus, reaching a high antibacterial activity of 96.6% in vitro and 97.3% in vivo with rapid 10 min NIR irradiation and 20 min US treatment. In addition, we firstly unveil the significant effect of Ti/PDA/BP-based sonodynamic therapy (SDT) on bacterial membrane and oxidative stress at the transcriptome level. Moreover, the Ti/PDA/BP coating remarkably promotes osteogenesis in vitro and bone-implant osseointegration in vivo. Overall, development of Ti/PDA/BP bioactive coating provides a new strategy for combating the implant associated infection.

Impact of bone-implant gap size on the interfacial osseointegration: an in vivo study

BackgroundThe bone-implant gap resulted from morphological mismatch between cervical bony endplates and implant footprint may have adverse impact on bone-implant interfacial osseointegration of cervical disc arthroplasty (CDA). The purpose of the study was to evaluate the impact of bone-implant gap size on the interfacial osseointegration in a rabbit animal model.MethodsA series of round-plate implants with different teeth depth (0.5 mm, 1.0 mm, 1.5 mm and 2.0 mm) was specifically designed. A total of 48 New Zealand white rabbits were randomly categorized into four groups by the implants they received (0.5 mm: group A, 1.0 mm: group B, 1.5 mm: group C, 2.0 mm: group D). At 4th and 12th week after surgery, animals were sacrificed. Micro-CT, acid fuchsin and methylene blue staining and hematoxylin and eosin (HE) staining were conducted.ResultsAt 4th week and 12th week after surgery, both micro-CT and HE staining showed more new bone formation and larger bone coverage in group A and group B than that in group C and group D. At 12th week, the bone biometric parameters were significantly superior in group C when compared with group D (p < 0.05). At 12th week, hard tissue slicing demonstrated larger portion of direct contact of new bone to the HA coating in group A and group B.ConclusionsBone-implant gap size larger than 1.0 mm negatively affected bone-implant osseointegration between compact bone and HA coated implant surface.

Improving the osseointegration and soft tissue sealing of zirconia ceramics by the incorporation of akermanite via sol infiltration for dental implants.

Zirconia ceramics are promising dental implant materials due to their high-grade biocompatibility, high mechanical strength, and distinctive aesthetic appearance. Nevertheless, zirconia ceramics are bio-inert with a lack of osseointegration and soft tissue sealing, which limits dental implant applications. As such, the fabrication of zirconia ceramics with high mechanical strength, excellent osseointegration and soft tissue sealing performance remains a great challenge in the dental restoration field. In this article, a novel zirconia ceramic with akermanite (AKT) modification by the negative pressure infiltration method is presented. The effects of AKT sol infiltration at different times on the morphology, phase composition, mechanical properties, bioactivity, osseointegration and soft tissue sealing of the modified zirconia ceramics have been systematically investigated. The modified zirconia ceramics feature excellent mechanical properties and significantly improved surface roughness, hydrophilia, and apatite mineralization ability as compared with unmodified zirconia ceramics. Furthermore, cell-culture experiment results indicated that the surface modification of zirconia ceramics could promote adhesion, spreading, migration, proliferation and osteogenic differentiation of mouse bone marrow stromal stem cells (mBMSCs), as well as the early adhesion, spreading, proliferation and fibroblast differentiation of human gingival fibroblasts (HGFs) in vitro. The prepared bioactive zirconia distinctively enhanced the alkaline phosphate (ALP) activity, osteogenesis-related gene expression of mBMSCs and fibroblast-related-gene expression of HGFs. The in vivo evaluation confirmed that 15-TZP ceramics could promote bone-implant osseointegration to the greatest extent as compared with pure zirconia ceramics. To conclude, our research has shown that AKT-modified zirconia ceramics can achieve bone integration and soft tissue sealing, indicating that they have a lot of potential for application as a novel dental implant material in the clinical setting.

A Review of Biomimetic Topographies and Their Role in Promoting Bone Formation and Osseointegration: Implications for Clinical Use.

The use of metallic and polymeric materials for implants has been increasing over the past decade. This trend can be attributed to a variety of factors including a significant increase in basic science research focused on implant material characteristics and how various surface modifications may stimulate osseointegration and, ultimately, fusion. There are many interbody fusion devices and dental implants commercially available; however, detailed information about their surface properties, and the effects that various materials and surface modifications may have on osteogenesis, is lacking in the literature. While the concept of bone-implant osseointegration is a relatively recent addition to the spine fusion literature, there is a comparatively large body of literature related to dental implants. The purpose of this article is to summarize the science of surface modified bone-facing implants, focusing on biomimetic material chemistry and topography of titanium implants, to promote a better understanding of how these characteristics may impact bone formation and osseointegration. This manuscript has the following aspects: highlights the role of titanium and its alloys as potent osteoconductive bioactive materials; explores the importance of biomimetic surface topography at the macro-, micro- and nano-scale; summarizes how material surface design can influence osteogenesis and immune responses in vitro; focuses on the kinds of surface modifications that play a role in the process. Biomimetic surface modifications can be varied across many clinically available biomaterials, and the literature supports the hypothesis that those biomaterial surfaces that exhibit physical properties of bone resorption pits, such as roughness and complex hierarchical structures at the submicron and nanoscale, are more effective in supporting osteoblast differentiation in vitro and osteogenesis in vivo.

Optimizing the strontium content to achieve an ideal osseointegration through balancing apatite-forming ability and osteogenic activity

Implant failure caused by unsatisfying osseointegration is still a noteworthy clinical problem. Strontium (Sr) has been confirmed to be a bioactive element that facilitates bone growth. In this study, Sr was surface incorporated in titanium (Ti) implant with different contents. The XRD results demonstrated that Sr existed mainly in the form of SrTiO3. All Sr-contained implants showed sustainable Sr2+ release behavior. Meanwhile, the Sr2+ release rate was proportional to the Sr content. The in vitro immersing test showed that the apatite-forming ability on the implant surface was decreased with the increase of Sr content. Conversely, the cell experiments manifested that implants with high content of Sr were more favorable to cell spreading, proliferation, osteogenic differentiation, and extracellular matrix mineralization. The in vivo implant experiment revealed that Sr-incorporation could improve osseointegration, new bone formation and mineralization, and bone-implant bonding strength. In addition, Ti5Sr, which possessed a combined good osteogenic activity and apatite-forming ability, exhibited the best in vivo overall performance. In summary, we first put forward the competitive effect of osteogenic activity and apatite-forming ability on bone-implant osseointegration, which would provide a new strategy for implant design.

A programmed surface on polyetheretherketone for sequentially dictating osteoimmunomodulation and bone regeneration to achieve ameliorative osseointegration under osteoporotic conditions

Polyetheretherketone (PEEK) is a desirable alternative to conventional biomedical metals for orthopedic implants due to the excellent mechanical properties. However, the inherent bioinertness of PEEK contributes to inferior osseointegration of PEEK implants, especially under pathological conditions of osteoporosis. Herein, a programmed surface is designed and fabricated on PEEK to dictate osteoimmunomodulation and bone regeneration sequentially. A degradable hybrid coating consisting of poly(lactide-co-glycolide) and alendronate (ALN) loaded nano-hydroxyapatite is deposited on PEEK and then interleukin-4 (IL-4) is grafted onto the outer surface of the hybrid coating with the aid of N2 plasma immersion ion implantation and subsequent immersion in IL-4 solution. Dominant release of IL-4 together with ALN and Ca2+ during the first few days synergistically mitigates the early acute inflammatory reactions and creates an osteoimmunomodulatory microenvironment that facilitates bone regeneration. Afterwards, slow and sustained delivery of ALN and Ca2+ in the following weeks boosts osteogenesis and suppresses osteoclastogenesis simultaneously, consequently ameliorating bone-implant osseointegration even under osteoporotic conditions. By taking into account the different phases in bone repair, this strategy of constructing advanced bone implants with sequential functions provides customizable and clinically viable therapy to osteoporotic patients.

Hierarchical microgroove/nanopore topography regulated cell adhesion to enhance osseointegration around intraosseous implants in vivo.

Implant surface topography plays a crucial role in achieving successful implantation. Simple and controllable surface topographical modifications are considered a promising method to accelerate bone osseointegration for biomedical applications. Moreover, comprehension of the mechanism between surface topography and cell osteogenic differentiation is vital for the manipulation of these processes to promote bone tissue regeneration. In this study, we investigated the effects of implant surfaces with various sized hierarchical microgroove/nanopore topographies on cell adhesion, osteogenesis, and their underlying mechanism both in vitro and in vivo. Our findings reveal that a titanium surface with an appropriately sized microgroove/nanopore topography (SLM-1MAH) exhibits the more satisfactory adhesive and osteogenic efficiency than the clinically used sand-blasted, large-grit, and acid-etched (SLA) surface. The underlying molecular mechanism lies in the activation of the integrin α2-PI3K-Akt signaling pathway, where the SLM-1MAH surface increased the protein expressions of integrin α2 (Itga2), phosphatidylinositol 3-kinase (PI3K), and phosphorylated serine/threonine kinase Akt (p-Akt) to enhance osteogenesis and osseointegration. Furthermore, the SLM-1MAH surface also displays better osseointegration efficiency with stronger bonding strength than that on the SLA surface. This work provides a novel strategy for implant surface topography design to improve bone-implant osseointegration.

Biomimetic hierarchical implant surfaces promote early osseointegration in osteoporotic rats by suppressing macrophage activation and osteoclastogenesis.

Successful implant-bone integration remains a formidable challenge in osteoporotic patients, because of excessive inflammatory reactions and osteoclastogenesis around the peri-implant bone tissue. This study designed biomimetic micro/sub-micro hierarchical surfaces on titanium implants based on natural bone hierarchical structures to mitigate macrophage-mediated inflammatory reactions, osteoclastogenesis, and osteogenesis in vitro, as well as promote early osseointegration in vivo. It was found that the biomimetic hierarchical surfaces inhibited M1 macrophage-mediated inflammatory reactions via suppression of the TLR2/NF-κB signaling pathway in vitro. Subsequently, osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was observed to be significantly enhanced on hierarchical surfaces in the presence of macrophage conditional media. Furthermore, osteoclast formation was also decreased by inhibiting the osteoclastogenesis regulatory factor NFATc-1 expression on hierarchical surfaces. In vivo, the implant with a micro/sub-micro hierarchical surface underwent rapid and early osseointegration, with the newly formed bone being tightly integrated with the implants. Hence, the hierarchical surface mitigated the inflammatory microenvironment around the implant, thereby inhibiting osteoclastogenesis. This study thus offers a novel biomimetic strategy for designing surface hierarchical topography to facilitate implant-bone osseointegration in osteoporotic patients.

Magnetron sputtering of strontium nanolayer on zirconia implant to enhance osteogenesis

The zirconia implants have a wide range of clinical applications, however, the biological inertness and lack of osteoinductive properties limit these applications. Strontium possesses superior biocompatibility and excellent osteogenic properties. To take advantage of these, the strontium titanate-coated zirconia implants were prepared in this study by sandblasting, acid etching, and magnetron sputtering, followed by the analysis of the biological behavior. Briefly, the zirconia sheets were polished and subjected to sandblasting and acid etching. Subsequently, a nano‑strontium titanate coating was developed on the sheets by magnetron sputtering. The specimens were characterized by scanning electron microscopy (SEM), water contact angle measurement (WCA) and EDS mapping, which confirmed the physical alternation and successful deposition of the strontium titanate coating. The in vitro experiments indicated that the majority of the filopodia and actin fibers of the MC3T3-E1 cells on SA-ZrO2/Sr possessed an optimal osteogenic property to promote the osteogenic differentiation. Moreover, the RT-PCR results revealed that SA-ZrO2/Sr significantly up-regulated the gene expression of Runx2, COL-1, ALP, OPG, OPN and OCN. Further, the in vivo evaluation confirmed that the SA-ZrO2/Sr implants promoted the bone-implant osseointegration to the greatest extent as compared to SA-ZrO2 and ZrO2 implant. Overall, the SA-ZrO2/Sr system was confirmed to be a promising implant, thus, providing new pathways for an effective implant design.

Novel Bionic Topography with MiR-21 Coating for Improving Bone-Implant Integration through Regulating Cell Adhesion and Angiogenesis.

Implant loosening is still the major form of the failure of artificial joints. Herein, inspired by the operculum of the river snail, we prepared a novel bionic micro/nanoscale topography on a titanium surface. This bionic topography promoted early cell adhesion through up-regulating the expression of ITG α5β1 and thus accelerated the following cell spreading, proliferation, and differentiation. Moreover, a miR-21 coating, which promoted the angiogenic differentiation of MSCs, was fabricated on the bionic topography. Benefiting from both bionic micro/nanoscale topography and miR-21, blood vessel growth and bone formation and mineralization around the implant, as well as bone-implant bonding strength, were significantly improved. Collectively, the present study highlights the combination of the bionic micro/nanoscale topography and miR-21 on promoting cell adhesion and angiogenic differentiation and improving in vivo angiogenesis and bone-implant osseointegration. This work provides a new train of thought propelling the development of implants for potential application in the orthopedics field.

A novel biocompatible PDA/IR820/DAP coating for antibiotic/photodynamic/photothermal triple therapy to inhibit and eliminate Staphylococcus aureus biofilm

Surgical site infection (SSI) with instrumentation is an undesired and troublesome complication in orthopaedics. Surgical debridement is currently the main treatment option. However, the poor prognosis remains the major problem and over 40% of patients needed additional surgery to remove the implant. To eliminate SSI, antibacterial and biocompatible implants are urgently needed. Herein, a novel biocompatible polydopamine (PDA)-IR820-Daptomycin (DAP) coating with triple therapy functions was successfully fabricated to enhance the anti-infection ability and osteogenic property of titanium implants. In which, PDA served as a biocompatible binder to immobilize IR820 and DAP, and possessed photothermal and osteogenic properties. The releasing of DAP inhibited the growth of Staphylococcus aureus and damaged the bacterial membrane. Meanwhile, after 808 nm laser irradiation, the combination of hyperthermia generated by PDA and singlet oxygen (1O2) produced by IR820 eradicated the biofilm noninvasively. Furthermore, this coating successfully accelerated glutathione (GSH) oxidation and destroyed the bacterial membrane, reaching an anti-bacterial efficiency of 97.2% in vitro. Additionally, the coating significantly stimulated the proliferation and osteogenic differentiation of rat bone marrow stem cells (rBMSCs). In vivo, Ti-PDA-IR820-DAP reached an anti-bacterial efficiency of 97.9% in a S. aureus biofilm-infected rat model with 15 min of irradiation at 50 °C and drastically promoted the bone-implant osseointegration in a rat femur condyle defect model. The present study demonstrates that combining antibiotics and phototherapy represents a feasible way to treat bone-implant-associated infections.

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.

The synergistic promotion of osseointegration by nanostructure design and silicon substitution of hydroxyapatite coatings in a diabetic model.

Accumulating evidence indicates much higher failure rates for biomedical titanium implants in diabetic patients. This phenomenon is attributed to impaired osteoblastic function, suppressed angiogenesis capacity, and abnormal osteoclast activation in diabetic patients. Our previous study demonstrated that titanium implants coated with highly crystalline nanostructured hydroxyapatite (nHA) promoted the osteogenic differentiation of bone marrow stromal cells (BMSCs) and bone-implant osseointegration under healthy conditions. Furthermore, recent studies showed that silicon-substituted biomaterials exhibited excellent osteogenesis and angiogenesis performance while repressing osteoclastogenesis. Hence, we proposed that a combination of nanostructural modification and Si substitution might produce synergetic effects to mitigate the impaired osseointegration of bone implants under diabetes mellitus (DM) conditions. To confirm this hypothesis, titanium implants coated with highly crystalline Si-substituted nHA (Si-nHA) were successfully fabricated via atmospheric plasma spraying combined with hydrothermal treatment. An in vitro study demonstrated that compared to the original HA coating, the nHA coating improved osteogenic and angiogenic differentiation and altered the OPG/RANKL ratio of DM-BMSCs. In addition, the Si-nHA coating further enhanced cell proliferation, improved osteogenic and angiogenic differentiation, and repressed osteoclastogenesis in DM-BMSCs. An in vivo study confirmed that the titanium implants coated with nHA or Si-nHA effectively promoted bone formation and bone-implant osseointegration in a diabetic rabbit model, with the Si-nHA coating exhibiting the best stimulatory effect. Collectively, the results suggest that the nanostructured topography and Si substitution act synergistically to ameliorate the poor bone regeneration and osseointegration associated with DM. Thus, the results provide a promising coating method for dental and orthopedic applications under diabetic conditions.

Nerve electrical stimulation enhances osseointegration of implants in the beagle

Dental implantation has been the primary method for the treatment of tooth loss, but longer than 3 months healing times are generally required. Because immediate load implants are suitable only for certain categories of implant patients, it has value to develop a novel method to facilitate the implant-bone osseointegration process. Cylindrical titanium implants were implanted in the tooth sockets of beagles, and microelectrode stimulation of the sympathetic nerves in the infraorbital nerve was performed after implantation for 1 week. The authors found that one-sided nerve stimulation was shown to evoke consistent electric potential changes in both sides of the infraorbital nerves. Moreover, after 4 weeks of implantation, more new bone was clearly observed around the implants in the beagles that received electrical stimulation treatment than was observed in the control animals. Furthermore, a higher mineralization density was measured in the new peri-implant bone tissues of the stimulated beagles when compared to controls. These results demonstrate that the simple and safe physical method of microelectrode stimulation to sympathetic nerves can promote the formation of new bone and the osseointegration of implants. This technique is worth promoting and has the potential to reduce the healing time of dental implantation in future clinical cases.

Effects of micro/nano strontium-loaded surface implants on osseointegration in ovariectomized sheep.

Poor osseointegration of dental implants often occurs in osteoporotic patients and processed implant surfaces could help to improve the dilemma. This study aimed to compare the effects of different titanium (Ti) surfaces on bone-implant osseointegration in ovariectomized (OVX) sheep. Four groups were included: smooth titanium (ST) was merely polished Ti; micro titanium (MT) was treated with hydrofluoric acid (HF) for 30 minutes; strontium-loaded nano titanium (NT-Sr) was formed by magnetron sputtering; strontium-loaded micro/nano titanium (MNT-Sr) was fabricated by HF etching combined with magnetron sputtering. The biological responses were evaluated by human bone marrow-derived mesenchymal stem cells (hBMMSCs) experiments in vitro. Osseointegration was evaluated in vivo after each surface implant was inserted into OVX sheep' mandibles. The numbers of adhered and mineralized hBMMSCs increased significantly in the MNT-Sr group. The bone-implant contact and the maximal pull-out force increased significantly with MNT-Sr surface. The bone volume ratio and trabecular number of the MNT-Sr group were significantly higher than others, whereas trabecular separation decreased. These results indicated that an MNT-Sr surface promotes the differentiation of hBMMSCs in vitro and enhances bone-implant osseointegration in vivo, which may be a promising option for clinical implants in osteoporotic patients.

Long-Term Prevention of Bacterial Infection and Enhanced Osteoinductivity of a Hybrid Coating with Selective Silver Toxicity.

Antibacterial and osteogenic design is required for ideal orthopedic implants. The excellent antimicrobial performance of silver nanoparticles (AgNPs) has attracted interest for the treatment of implant-related infections. However, the dose-dependent cytotoxicity of silver and its negative impact on bone implants restrict the further use of AgNPs coatings. Therefore, a hybrid coating containing polydopamine (PDA), hydroxyapatite (HA), AgNPs, and chitosan (CS) is prepared. Organic chelators CS and PDA that have promising biocompatibility are used to prevent the rapid release of silver ions from the AgNPs coating. The double chelating effect of PDA and CS significantly reduces silver ion release from the hybrid coating. The coating exhibits excellent anti-biofilm efficiency of 91.7%, 89.5%, and 92.0% for Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia coli, respectively. In addition, the coating can significantly stimulate osteogenic differentiation of MC3T3-E1 cells and promote bone-implant osseointegration in vivo as compared to that in the control group. The longitudinal biosafety of the coating is confirmed in vivo by histological evaluation and blood tests. The results of this study indicate that the hybrid coating exhibits antibacterial properties as well as allow bone-implant osseointegration, thereby providing insight into the design of multifunctional implants for long-term orthopedic applications.

A Quantitative Approach for the Bone-implant Osseointegration Assessment Based on Ultrasonic Elastic Guided Waves

Quantitative and reliable monitoring of osseointegration will help further evaluate the integrity of the orthopaedic construct to promote novel prosthesis design and allow early mobilisation. Quantitative assessment of the degree or the lack of osseointegration is important for the clinical management with the introduction of prosthetic implants to amputees. Acousto-ultrasonic wave propagation has been used in structural health monitoring as well as human health monitoring but so far has not extended to osseointegrated implants or prostheses. This paper presents an ultrasonic guided wave approach to assess the osseointegration of a novel implant. This study explores the potential of integrating structural health monitoring concepts into a new osseointegrated implant. The aim is to demonstrate the extension of acousto-ultrasonic techniques, which have been widely reported for the structural health monitoring of engineering structures, to assess the state of osseointegration of a bone and implant. To illustrate this potential, this paper will report on the experimental findings which investigated the unification of an aluminium implant and bone-like geometry surrogate. The core of the test specimen is filled with silicone and wrapped with plasticine to simulate the highly damped cancellous bone and soft tissue, respectively. To simulate the osseointegration process, a 2-h adhesive epoxy is used to bond the surrogate implant and a bone-like structure. A series of piezoelectric elements are bonded onto the surrogate implant to serve as actuators and sensors. The actuating piezoelectric element on an extramedullary strut is excited with a 1 MHz pulse signal. The reception of the ultrasonic wave by the sensing elements located on the adjacent and furthest struts is used to assess the integration of this implant to the parent bone structure. The study shows an Osseointegration Index can be formulated by using engineering and acousto-ultrasonic methods to measure the unification of a bone and implant. This also highlights a potential quantitative evaluation technique regardless of bone-implant geometry and soft tissue damping.