Essential neural anatomy for creating a clinically translatable osseointegrated neural interface for prosthetic control in sheep

Aim:Ovine models for osseointegrated prosthetics research are well established,but do not consider neural control of advanced prostheses.The validity of interfacing technologies,such as the Osseointegrated Neural Interface(ONI),in their ability to provide communication between native nerves and advanced prosthetics is required,necessitating a stable,longitudinal large animal model for testing.The objective of this study is to provide a detailed anatomic description of the major nerves distal to the carpal and tarsal joints,informing the creation of a chronic ONI for prosthetic control in sheep.Methods:Six pelvic and six thoracic cadaveric limbs from mature female,non-lactating sheep were utilized.Radiographs were obtained to determine average bone length,medullary canal diameter,and cortical bone thickness.Microsurgical dissection was performed to discern topographical neuroanatomy and average circumferences of the major nerves of the pelvic and thoracic limbs.Histologic analysis was performed.A surgical approach for the creation of ONI was designed.Results:Average metacarpal and metatarsal length was 15.0 cm(±0.0)and 19.7 cm(±1.0),respectively.Average intramedullary canal diameter was 12.91 mm(±3.69)for forelimbs and 12.60 mm(±3.69)for hindlimbs.The thoracic limb nerves consisted of one dorsal and three ventral nerves,with an average circumference of 5.14 mm(±2.00)and 5.05 mm(±1.06),respectively.Pelvic limb nerves consisted of two dorsal and one ventral nerve with an average circumference of 6.27 mm(±1.79)and 5.40 mm(±0.53),respectively.Conclusions:These anatomic data inform the surgical approach and manufacture of a sensory ONI for chronic testing in awake,freely ambulating animals for future clinical translation.

Impact of High Sodium Diet on Neovascularization and Osseointegration around Titanium Implant:An in Vivo and in Vitro Study

Objective A high sodium(HS)diet is believed to affect bone metabolism processes.Clarifying its impact on osseointegration of titanium(Ti)implants holds significant implications for postoperative dietary management of implanted patients.Methods This investigation probed the impact of sodium ions(Na^(+))on neovascularization and osteogenesis around Ti implants in vivo,utilizing micro-computed tomography,hematoxylin and eosin staining,and immunohistochemical analyses.Concurrently,in vitro experiments assessed the effects of varied Na^(+)concentrations and exposure durations on human umbilical vein endothelial cells(HUVECs)and MC3T3-E1 cells.Results In vivo,increased dietary sodium(0.8%-6.0%)led to a substantial decline in CD34 positive HUVECs and new bone formation around Ti implants,alongside an increase in inflammatory cells.In vitro,an increase in Na^(+)concentration(140-150 mmol/L)adversely affected the proliferation,angiogenesis,and migration of HUVECs,especially with prolonged exposure.While MC3T3-E1 cells initially exhibited less susceptibility to high Na^(+)concentrations compared to HUVECs during short-term exposure,prolonged exposure to a HS environment progressively diminished their proliferation,differentiation,and osteogenic capabilities.Conclusion These findings suggest that HS diet had a negative effect on the early osseointegration of Ti implants by interfering with the process of postoperative vascularized bone regeneration.

Elimination of methicillin‑resistant Staphylococcus aureus biofilms on titanium implants via photothermally‑triggered nitric oxide and immunotherapy for enhanced osseointegration

Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to explore more effective approaches for the treatment of MRSA biofilm infections.Methods:Herein,an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles(PDA),nitric oxide(NO)release donor sodium nitroprusside(SNP)and osteogenic growth peptide(OGP)onto Ti implants,denoted as Ti-PDA@SNP-OGP.The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy,X-ray photoelectron spectroscope,water contact angle,photothermal property and NO release behavior.The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe,1-N-phenylnaphthylamine assay,adenosine triphosphate intensity,O-nitrophenyl-β-D-galactopyranoside hydrolysis activity,bicinchoninic acid leakage.Fluorescence staining,assays for alkaline phosphatase activity,collagen secretion and extracellular matrix mineralization,quantitative real‑time reverse transcription‑polymerase chain reaction,and enzyme-linked immunosorbent assay(ELISA)were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells(MSCs),RAW264.7 cells and their co-culture system.Giemsa staining,ELISA,micro-CT,hematoxylin and eosin,Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms,inhibition of inflammatory response,and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo.Results:Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light(NIR)irradiation,and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species(ROS)-mediated oxidative stress,destroying bacterial membrane integrity and causing leakage of intracellular components(P<0.01).In vitro experiments revealed that Ti-PDA@SNP-OGP not only facilitated osteogenic differentiation of MSCs,but also promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype(P<0.05 or P<0.01).The favorable osteo-immune microenvironment further facilitated osteogenesis of MSCs and the anti-inflammation of RAW264.7 cells via multiple paracrine signaling pathways(P<0.01).In vivo evaluation confirmed the aforementioned results and revealed that Ti-PDA@SNP-OGP induced ameliorative osseointegration in an MRSA-infected femoral defect implantation model(P<0.01).Conclusions:Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries.

Recent advances in bio-functional Ta-based bone materials:materials design and bioactivity

Ta-based materials have gained significant interest for bioimplantable scaffolds because of their appropriate mechanical characteristics and biocompatibility.To overcome the serious limitation of bioinertness,there have been many efforts to enhance the bioactivity and osseointegration of Ta-based scaffolds through morphostructural and surface modifications.As scaffolds are implantable devices,sufficient bioactivity is needed to trigger the cellular functions required for tissue engineering.Consequently,a combination of materials and bioscience is needed to develop efficient Ta-based scaffolds,although reviews of this interdisciplinary field remain limited.This review aims to provide an overview of the main strategies to enhance the bioactivity of Ta-based scaffolds,describing the basic mechanisms and research methods of osseointegration,and the approaches to enhance bioactivity and osseointegration.These approaches are divided into three main sections:(i)alteration of the micromorphology,(ii)customization of the scaffold structure,and(iii)functionalization modifications(through alloying or the addition of surface coatings).Also provided are recent advances regarding biocompatibility assessment in vitro,osseointegration properties in vivo,and clinical trial results.

Optimising soft tissue in-growth in vivo in additive layer manufactured osseointegrated transcutaneous implants

Osseointegrated transcutaneous implants could provide an alternative and improved means of attaching artificial limbs for amputees,however epithelial down growth,inflammation,and infections are common failure modalities associated with their use.To overcome these problems,a tight seal associated with the epidermal and dermal adhesion to the implant is crucial.This could be achieved with specific biomaterials(that mimic the surrounding tissue),or a tissue-specific design to enhance the proliferation and attachment of dermal fibroblasts and keratinocytes.The intraosseous transcutaneous amputation prosthesis is a new device with a pylon and a flange,which is specifically designed for optimising soft tissue attachment.Previously the flange has been fabricated using traditional machining techniques,however,the advent of additive layer manufacturing(ALM)has enabled 3-dimensional porous flanges with specific pore sizes to be used to optimise soft tissue integration and reduce failure of osseointegrated transcutaneous implants.The study aimed to investigate the effect of ALM-manufactured porous flanges on soft tissue ingrowth and attachment in an in vivo ovine model that replicates an osseointegrated percutaneous implant.At 12 and 24 weeks,epithelial downgrowth,dermal attachment and revascularisation into ALM-manufactured flanges with three different pore sizes were compared with machined controls where the pores were made using conventional drilling.The pore sizes of the ALM flanges were 700,1000 and 1250μm.We hypothesised that ALM porous flanges would reduce downgrowth,improve soft tissue integration and revascularisation compared with machined controls.The results supported our hypothesis with significantly greater soft tissue integration and revascularisation in ALM porous flanges compared with machined controls.

Effects of pore size and porosity of surface-modified porous titanium implants on bone tissue ingrowth

The effects of surface-modified porous titanium implants with different porosities and pore sizes on osseointegration were investigated in vivo.Three porous titanium implants(A30,A40 and A50 containing volume fractions of space-holder NaCl being 30%,40%and 50%,respectively)were manufactured by metal injection moulding(MIM).The surface-modified implants were implanted into muscles and femurs of hybrid male dogs.Interface osteogenic activity and histological bone ingrowth of porous titanium implants were evaluated at 28,56 and 84 d.The results showed that when additive space-holder amount of NaCl increased from 30%to 50%(volume fraction),the general porosity and mass fraction of macropores of porous titanium rose from 42.4%to 62.0%and from 8.3%to 69.3%,respectively.Histologic sections and fluorescent labeling showed that the A50 implant demonstrated a significantly higher osteogenic capacity at 28 d than other implants.Bone ingrowth into the A30 implant was lower than that into other implants at 84 d.Therefore,the pore structure of A50 implant was suitable for new bone tissue to grow into porous implant.

Dental implant treatment for renal failure patients on dialysis:a clinical guideline

Chronic kidney disease （CKD） is a worldwide public health problem that is growing in prevalence and is associated with severe complications. During the progression of the disease, a majority of CKD patients suffer oral complications. Dental implants are currently the most reliable and successful treatment for missing teeth. However, due to complications of CKD such as infections, bone lesions, bleeding risks, and altered drug metabolism, dental implant treatment for renal failure patients on dialysis is more challenging. In this review, we have summarized the characteristics of CKD and previous publications regarding dental treatments for renal failure patients. In addition, we discuss our recent research results and clinical experience in order to provide dental implant practitioners with a clinical guideline for dental implant treatment for renal failure patients undergoing hemodialysis.

Impact of osteoporosis in dental implants:A systematic review

AIM: To assess the failure and bone-to-implant contact rate of dental implants placed on osteoporotic subjects. METHODS: Extensive examination strategies were created to classify studies for this systematic review. MEDLINE(via Pub Med) and EMBASE database were examined for studies in English up to and including May 2014. The examination presented a combination of the MeS H words described as follow: "osteoporosis" or "osteopenia" or "estrogen deficiency" AND "implant" or "dental implant" or "osseointegration". Assessment of clinical and/or histological peri-implant conditions in osteoporosis subjects treated with titanium dental implants. The examination included a combination of the MeS H terms described as follow: "osteoporosis" or "osteopenia" or "estrogen deficiency" AND "implant" or "dental implant" or "osseointegration".RESULTS: Of 943 potentially eligible articles, 12 were included in the study. A total of 133 subjects with osteoporosis, 73 subjects diagnosed with osteopenia and 708 healthy subjects were assessed in this systematic review. In these subjects were installed 367, 205, 2981 dental implants in osteoporotic, osteopenic and healthy subjects, respectively. The failure rate of dental implant was 10.9% in osteoporotic subjects, 8.29% in osteopenic and 11.43% in healthy ones. Bone-to-implant contact obtained from retrieved implants ranged between 49.96% to 47.84%, for osteoporosis and non-osteoporotic subjects. CONCLUSION: Osteoporotic subjects presented higher rates of implant loss, however, there is a lower evidence to strengthen or refute the hypothesis that osteoporosis may have detrimental effects on bone healing. Consequently, final conclusions regarding the effect of osteoporosis in dental implant therapy cannot be made at this time. There are no randomized clinical trial accessible for evaluation and the retrospectivenature of the evaluated studies shall be taken in account when interpreting this study.

Effect of High Positive Acceleration(+Gz) Environment on Dental Implant Osseointegration:A Preliminary Animal Study

Objective To observe the effect of high positive acceleration(+Gz) environment on dental implant osseointegration in a rabbit model and to investigate its mechanism.Methods Forty-eight New Zealand white rabbits were randomly divided into 6 groups. The rabbit’s mandibular incisors were extracted and 1 implant was placed in each socket immediately. After 1 week of rest, the rabbits were exposed to a high +Gz environment, 3 times a week. The rabbits were sacrificed at 3 weeks(2 weeks +Gz exposure), 5 weeks(4 weeks +Gz exposure), and 12 weeks(4 weeks +Gz exposure and 7 weeks normal environment) after surgery, respectively. Specimens were harvested for micro-CT scanning, histological analysis, and real-time polymerase chain reaction examination.Results Compared with those in the control group, the mRNA expression levels of bone morphogenetic protein-2(BMP-2), osteopontin(OPN), and transforming growth factor-β1(TGF-β1)were significantly lower(P < 0.05), while the mRNA expression level of receptor activator of nuclear factor κB ligand(RANKL) and the RANKL/osteoprotegerin(OPG) ratio were significantly higher(P < 0.05)at 3 weeks;values of bone volume fraction, trabecular number, bone-implant contact(BIC), and TGF-β1 and OPG mRNA expression levels were significantly lower(P < 0.05), and the value of trabecular separation, RANKL mRNA expression level and RANKL/OPG ratio were significantly higher(P < 0.05) at 5 weeks;and the value of BIC was still significantly lower(P < 0.05) at 12 weeks in the experimental group.Conclusion Early exposure to the high +Gz environment after implant surgery might have an adverse effect on osseointegration, and its mechanism could be related to the inhibition of osteoblast activity and promotion of osteoclast activity.

Approaches to promoting bone marrow mesenchymal stem cell osteogenesis on orthopedic implant surface

Bone marrow-derived mesenchymal stem cells(BMSCs)play a critical role in the osseointegration of bone and orthopedic implant.However,osseointegration between the Ti-based implants and the surrounding bone tissue must be improved due to titanium’s inherent defects.Surface modification stands out as a versatile technique to create instructive biomaterials that can actively direct stem cell fate.Here,we summarize the current approaches to promoting BMSC osteogenesis on the surface of titanium and its alloys.We will highlight the utilization of the unique properties of titanium and its alloys in promoting tissue regeneration,and discuss recent advances in understanding their role in regenerative medicine.We aim to provide a systematic and comprehensive review of approaches to promoting BMSC osteogenesis on the orthopedic implant surface.

Bone integration properties of antibacterial biomimetic porous titanium implants

A novel antibacterial biomimetic porous titanium implant with good osseointegration was prepared by freeze-casting and thermal oxidation.Bone integration properties of the porous titanium implant were evaluated by cell proliferation assay,alkaline phosphatase activity assay,X-ray examination and hard bone tissue biopsy.The in vitro cell proliferation and the level of differentiation of the group with a modified nano-porous implant surface were significantly higher than those in the group without surface modification and the dense titanium control group(P<0.05).In vivo,bone growth and osteogenesis were found in the experimental groups with modified and unmodified porous titanium implants;osteoblasts in the modified group had more mature differentiation in the pores compared to the unmodified group.Such implants can form solid,biologically compatible bone grafts with bone tissues,exhibiting good osseointegration.

Adhesion-enhancing coating embedded with osteogenesis-promoting PDA/HA nanoparticles for peri-implant soft tissue sealing and osseointegration

Following dental implantation,the characteristic bacterial milieu of the oral cavity may lead to peri-implant inflammation,which can negatively impact osseointegration and cause implant failure.To improve soft tissue sealing around the implant,enhance osseointegration,and improve implant success rates,this paper proposes a composite multifunctional coating(PHG)prepared using gelatin and polydopamine/hydroxyapatite nanoparticles,investigates the effects of this novel coating on cell adhesion,proliferation,antibacterial activity,osteogenic differentiation,and evaluates its immune-related properties.The PHG coating was proved to have satisfactory hydrophilicity and wettability for cell attachment.Furthermore,it improved the expression of adhesion-related genes and proteins in human gingival fibroblasts,indicating its adhesion-promoting effect.Additionally,bone marrow mesenchymal stem cells exhibited strong osteogenic differentiation potential and mineralization on PHG-coated surfaces.Notably,the PHG coating exhibited antibacterial activity against Streptococcus mutans,as well as anti-inflammatory effects,potentially via the regulation of macrophages.Therefore,the proposed PHG coating may promote soft tissue sealing and bone bonding,providing a potential strategy for the surface modification of dental implants.

Acetabular revisions using porous tantalum components: A retrospective study with 5-10 years follow-up

AIM To evaluate the clinical and X-ray results of acetabular components and tantalum augments in prosthetic hip revisions.METHODS Fifty-eight hip prostheses with primary failure of the acetabular component were reviewed with tantalum implants. The clinical records and X-rays of these cases were retrospectively reviewed. Bone defect evaluations were based on preoperative CT scans and classified according to Paprosky criteria of Radiolucent lines and periprosthetic gaps; implant mobilization and osteolysis were evaluated by X-ray. An ad hoc database was created and statistical analyses were performed with SPSS software(IBM SPSS Statistics for Windows, version 23.0). Statistical analyses were carried out using the Student's t test for independent and paired samples. A P value of < 0.05 was considered statistically significant and cumulative survival was calculated by the KaplanMeier method.RESULTS The mean follow-up was 87.6 ± 25.6 mo(range 3-120 mo). 25 cases(43.1%) were classified as minor defects, and 33 cases(56.9%) as major defects. The preoperative HHS rating improved significantly from a mean of 40.7 ± 6.1(range: 29-53) before revision, to a mean of 85.8 ± 6.1(range: 70-94) at the end of the follow-up(Student's t test for paired samples: P < 0.001). Considering HHS only at the end of follow-up, no statistically significant difference was observed between patients with a major or minor defect(Student's t test for independent samples: P > 0.05). Radiolucent lines were found in 4 implants(6.9%). Postoperative acetabular gaps were observed in 5 hips(8.6%). No signs of implant mobilization or areas of periprosthetic osteolysis were found in the x-rays at the final follow-up. Only 3 implants failed: 1 case of infection and 2 cases of instability. Defined as the end-point, cumulative survival at 10 years was 95%(for all reasons) and 100% for aseptic loosening of the acetabular component.CONCLUSION The medium-term use of prosthetic tantalum components in prosthetic hip revisions is safe and effective in a wide variety of acetabular bone defects.

Enhanced Biocompatibility and Osseointegration of Calcium Titanate Coating on Titanium Screws in Rabbit Femur

This study aimed to examine the biocompatibility of calcium titanate(CaTiO3) coating prepared by a simplified technique in an attempt to assess the potential of CaTiO3coating as an alternative to current implant coating materials. CaTiO3-coated titanium screws were implanted with hydroxyapatite(HA)-coated or uncoated titanium screws into medial and lateral femoral condyles of 48 New Zealand white rabbits. Imaging, histomorphometric and biomechanical analyses were employed to evaluate the osseointegration and biocompatibility 12 weeks after the implantation. Histology and scanning electron microscopy revealed that bone tissues surrounding the screws coated with CaTiO3were fully regenerated and they were also well integrated with the screws. An interfacial fibrous membrane layer, which was found in the HA coating group, was not noticeable between the bone tissues and CaTiO3-coated screws. X-ray imaging analysis showed in the CaTiO3coating group, there was a dense and tight binding between implants and the bone tissues; no radiation translucent zone was found surrounding the implants as well as no detachment of the coating and femoral condyle fracture. In contrast, uncoated screws exhibited a fibrous membrane layer, as evidenced by the detection of a radiation translucent zone between the implants and the bone tissues. Additionally, biomechanical testing revealed that the binding strength of CaTiO3coating with bone tissues was significantly higher than that of uncoated titanium screws, and was comparable to that of HA coating. The study demonstrated that CaTiO3coating in situ to titanium screws possesses great biocompatibility and osseointegration comparable to HA coating.

Early Osseointegration of Implants with Cortex-like TiO2 Coatings Formed by Micro-arc Oxidation:A Histomorphometric Study in Rabbits

In our previous studies, a novel cortex-like Ti O2 coating was prepared on Ti surface through micro-arc oxidation（MAO） by using sodium tetraborate as electrolyte, and the effects of the coating on cell attachment were testified. This study aimed to investigate the effects of this cortex-like MAO coating on osseointegration. A sand-blasting and acid-etching（SLA） coating that has been widely used in clinical practice served as control. Topographical and chemical characterizations were conducted by scanning electron microscopy, energy dispersive X-ray spectrometer, X-ray diffraction, contact angle meter, and step profiler. Results showed that the cortex-like coating had microslots and nanopores and it was superhydrophilic, whereas the SLA surface was hydrophobic. The roughness of MAO was similar to that of SLA. The MAO and SLA implants were implanted into the femoral condyles of New Zealand rabbits to evaluate their in-vivo performance through micro-CT, histological analysis, and fluorescent labeling at the bone-implant interface four weeks after surgery. The micro-CT showed that the bone volume ratio and mean trabecular thickness were similar between MAO and SLA groups four weeks after implantation. Histological analysis and fluorescent labeling showed no significant differences in the bone-implant contact between the MAO and SLA surfaces. It was suggested that with micro/nanostructure and superhydrophilicity, the cortex-like MAO coating causes excellent osseointegration, holding a promise of an application to implant modification.

Effect of a Hybrid Micro/Nano-integrated Titanium Surface on Behavior of Rat Osteoblasts

The objective of this study was to investigate the effect of a new combined micro/nanoscale implant surface feature on osteoblasts＇ behaviors including cell morphology, adhesion, proliferation, differentiation, and mineralization in vitro. A new micro/nano-hybrid topography surface was fabricated on commercial pure titanium（Cp Ti） by a two-step sandblasted acid-etching and subsequent alkali-and heattreatment（SA-AH）. The conventional sandblasted/acid-etching（SA） treatment and alkali and heat（AH） treatment were also carried out on the Cp Ti as controls. Surface microstructures of the Ti disc samples were assessed by scanning electron microscopy（SEM）. The neonatal rat calvaria-derived osteoblasts were seeded on these discs and the initial cell morphology was evaluated by SEM and immunofluorescence. Initial adhesion of the cells was then assayed by DAPI staining at 1, 2, and 4 h after seeding. The Cell Counting Kit-8（CCact K8） assay, gene expression of osteoblastic markers（ALP, Col 1, OCN, BSP, OSX, Cbfα1） and Alizarin Red S staining assays were monitored respectively for cell proliferations, differentiation and mineralization. The results show significant differences in osteoblast＇s behaviors on the four kinds of Ti surfaces. Compared with Cp Ti surface, the SA and AH treatment can significantly promote cell adhesion, differentiation and mineralization of osteoblasts. In particular, the combined SA and AH treatments exhibit synergistic effects in comparison with the treatment of SA and AH individually, and are more favorable for stimulating a series of osteogenous responses from cell adhesion to mineralization of osteoblasts. In summary, this study provides some new evidence that the integrated micro/nanostructure on the Cp Ti surface may promote bone osseointegration between the Ti implantbone interfaces in vitro.

Evaluation of the osseointegration of dental implants coated with calcium carbonate:an animal study

In an attempt to overcome the limitations of titanium in dental and orthopaedic clinical applications, a new method has been developed to prepare calcium carbonate coatings on sandblasted and acid-etched （SA） titanium implants. The purpose of this study was to investigate the effect of calcium carbonate-SA （CC-SA） implants on osseointegration in vivo. The surfaces of SA and CC-SA implants were characterised for surface morphology and surface chemistry. Subsequently, these two kinds of implants were implanted in the femoral condyles of rabbits. The implants were retrieved and prepared for histological and histomorphometric evaluation 1, 2, 4, 8 and 12 weeks after implantation. Significantly higher values of bone-to-implant contact of the entire implant except the gap area （BIC_ALL） and the bone-to-implant contact of the gap area （BIC_GAP） were found in animals with the CC-SA implants than in those with the SA implants at 4 weeks. Higher values of total gap bone were found in those with the CC-SA implants than in those with the SA implants at 1, 2 and 4 weeks. In conclusion, the current findings demonstrate that the calcium carbonate coating can improve and accelerate the early ingrowth of bone and osseointegration at the early healine phase. This may reduce clinical healinE times and thus improve implant success rates.

Initial Stability Study of Calcium Phosphate Coated Dental Implants

Thin film of biodegradable calcium phosphate coated on threaded commercially pure titanium （ cp- Ti ） dental implants has been investigated as one of alternatives to eliminate the problem of the long- term instability of plasma sprayed HA coated implants. In order to compare in-vivo bone-to-implant response behavior among as-machined, HA coated and CMP coated groups, each group was implanted into New Zealand white mature male rabbits for 2 and 6 weeks, and then in-vivo biological behavior was examined in terms of H＆E staining. Initial stability and removable torques of implants were compared among three groups. Measured removable torque of CMP coated specimen at 6 weeks after inplantation was significantly higher than that of non-coated group, but slightly lower than that of HA coated group, without any inflammatory response at the surrounding of the implants. The initial stability （ ISQ value ; implant stability quotient ） of CMP coated specimen at 2 weeks after implantation was slightly lower than that of HA coated group and significantly higher than that of non-coated group. However, after 6 weeks, ISQ value of CMP coated group was slightly higher than that of HA coated group and significantly higher than that of non-coated group.

The signaling pathway in modulating bone metabolism after dental implant in diabetes

Diabetes Mellitus is a systematic disease with complications in multi-organs,including decreased implant osseointegration and a high failure rate of dental transplants.Accumulating evidence indicates that the signaling pathway directly impacts the process of bone metabolism and inflammatory response implicated with dental implants in diabetic patients.This review summarizes the recent advance in signaling pathways regulate osseointegration and inflammatory response in dental transplantation,aiming to identify the potential therapeutic target to reduce the dental transplant failure in diabetes patients,with emphasis on the surface characteristics of the implant,inflammatory signaling,AMPK,PPARγ,WNT,ROS,and adiponectin signaling.

The role of exosomes in bone remodeling and osseointegration of implants

Dental implant is an effective method in the treatment of missing teeth.The process of osseointegration of implant teeth involves the coordinated operation of immune system and bone system.The interaction between cells is closely related to bone formation and repair.Exosomes are important intercellular communication molecules.They were originally found in the supernatant of sheep erythrocytes cultured in vitro.They are micro vesicles with a diameter of 40~150 nm.They exist in a variety of cells and body fluids.They enter the target cells by endocytosis and transport,affecting the expression of cell genes and changing the fate of cells.It has an important regulatory function in the microenvironment of implant bone binding.It plays a role in bone remodeling through small molecular RNA,specific proteins and other growth factors secreted by different cells.This article reviews the role of bone derived cellderived exosomes in bone remodeling and their function in implant osseointegration.