Improved Osteointegration of Ti-6Al-4V-implants of Different Surface Texture by the Use of Bone Morphogenetic Protein-3 (BMP-3)

Half of altogether 60 cylindrical implant devices made of titanium-aluminum-vanadium alloy （ Ti-6Al-4V） were plusna-sprayed with a hydroxyapatite-couting and the other half had a corundum blasted porous surface. 15 implants of each group of the titanium test buplants were coated with 230 μg porcine, high-purified BMP- 3-precipitute per implant. In each case a BMP- 3-couted and an uncoated control-device were implanted into the femoral part of the putellofemoral joint of the right and left leg of 30 adult giant rabbits. Histomorphological and histomorphometrical we found in both groups with BMP- 3-coated test devices an improved osteointegrution. Stutistical evaluation using the t-test for matched samples showed 5 weeks after surgery a significant higher volume of tony formed bone of the BMP- 3-coated corundum- blasted or hydroxyapathe- coated Ti- 6Al- 4 V test devices compared to the non-couted controls of the same t）pe （p 〈 0.01, t-test for matched samples）. In both implant groups with BMP-couting a synergetic effect was verifiable although the bone ongrowth in the hydroxyaputite coated implants was more extensive than in the corundum blasted implants. Light microscopy demonstrated osteointegrution without connective tissue membrane around the surface of the implants. Our results indicate that composite metal implants,as used in endoprosthetics and implantology , are suitable carriers for BMP- 3 and im proved fixation of the implants can be achieved. The hydroxyapatite surface is superior to the corundum-blasted surface with regards to the observed parameters because of its pronounced bioactivity and its osteoconductive characteristics.

Accelerated and enhanced osteointegration of MAO-treated implants:histological and histomorphometric evaluation in a rabbit model

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.

Immunomodulation and osteointegration of infected implants by ion-riched and hierarchical porous TiO_(2)matrix

Infection is a main cause of implant failure.The microenvironment cell experiencing after antimicrobial therapy of infected implants is very crucial for immunomodulation and subsequent osteointegration.Based on the superiority of photothermal therapy in anti-infection,a matrix of nanograined TiO_(2)with(Si/P)-dual ions and hierarchical nano/microporous topography is developed on Ti implant by micro-arc oxidation.It shows good photothermal properties due to the lattice distortion induced by ion doping and can kill bacteria with near-infrared(NIR)light irradiation efficiently.Due to the combined action of porous topography and release of Si/P ions,the TiO_(2)matrix achieves M1-to-M_(2)phenotype switch of macrophages timely at different simulating infection stage and accelerates recruitment,proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.In vivo,the TiO_(2)matrix also shows desired antibacterial performance after photothermal therapy and exhibits outstanding immunomodulatory ability and new bone formation efficiency.This study provides a promising TiO_(2)matrix applied in clinic for settling implant infection by NIR light irradiation and promoting bone regeneration through osteoimmunomodulation.

An in vivo study on the effect of coating stability on osteointegration performance of collagen/hyaluronic acid multilayer modified titanium implants

Aseptic loosening of implant is one of the main causes of Ti-based implant failure.In our previous work,a novel stable collagen/hyaluronic acid(Col/HA)multilayer modified titanium coatings(TCs)was developed by layer-by-layer(LBL)covalent immobilization technique,which showed enhanced biological properties compared with TCs that were physically absorbed with Col/HA multilayer in vitro.In this study,a rabbit model with femur condyle defect was employed to compare the osteointegration performance of them.Results indicated that Col/HA multilayer with favourable stability could better facilitate osteogenesis around implants and bone-implant contact.The Col/HA multilayer covalentimmobilized TC may reduce aseptic loosening of implant.

A model of bone adaptation as a topology optimization process with contact

Topology optimization is presently used in most diverse scientific, technologic and industrial areas, including biomechanics. Bone remodelling models and structural optimization has mutually provided inspiration for new developments in biomechanics and biomedicine. Considering that bone has the ability to adapt its internal structure to mechanical loading (Wolff’s law and Roux’s paradigm), it is possible to model the behaviour of the bone structure by the use of a topology optimization methodology whose optimization variables can be the relative densities and the orthotropic directions. In this work, the internal bone adaptation of a proximal femur is considered. The bone-remodelling scheme is numerically described by a time-dependent evolutionary procedure with anisotropic material parameters. The remodelling rate equation is obtained from the structural optimization task of maximizing the stiffness subject to a biological cost associated with metabolic maintenance of bone tissue in time. The situation of multiple load conditions is considered for a three-dimensional finite element model of the proximal femur. The bone density distribution of a real femur is used as the initial design for the onset of the remodelling mechanism. Examples of bone adaptation resulting from load changes are presented. The three-dimensional finite element model of the proximal femur with initial bone density distribution was adapted to implant a cementless stem. A remeshing technique is used to assign the bone relative density distribution to the new geometry and mesh. The time adaptation of the bone is assessed considering contact with friction at the bone-stem interface. Results of bone density evolution and osteointegration distribution are obtained.

Role of pulsed electromagnetic fields after joint replacements

Although the rate of patients reporting satisfaction is generally high after joint replacement surgery, up to 23% after total hip replacement and 34% after total knee arthroplasty of treated subjects report discomfort or pain 1 year after surgery. Moreover, chronic or subacute inflammation is reported in some cases even a long time after surgery. Another open and debated issue in prosthetic surgery is implant survivorship, especially when related to good prosthesis bone ingrowth. Pulsed Electro Magnetic Fields(PEMFs) treatment, although initially recommended after total joint replacement to promote bone ingrowth and to reduce inflammation and pain, is not currently part of usual clinical practice. The purpose of this review was to analyze existing literature on PEMFs effects in joint replacement surgery and to report results of clinical studies and current indications. We selected all currently available prospective studies or RCT on the use of PEMFs in total joint replacement with the purpose of investigating effects of PEMFs on recovery, pain relief and patients’ satisfaction following hip, knee or shoulder arthroplasty. All the studies analyzed reported no adverse effects, and good patient compliance to the treatment. The available literature shows that early control of joint inflammation process in the first days after surgery through the use of PEMFs should be considered an effective completion of the surgical procedure to improve the patient’s functional recovery.

Self-Assembled Monolayers (SAMs): Which Perspectives in Implant Dentistry?

Self-assembled monolayers (SAMs) are ordered organic films formed by adsorption of an active organic coating on a solid surface. Their formation provides an alternative, highly innovative, to current traditional chemical treatments of the titanium surfaces. For this reason the structural phases, the formation and the growth of SAMs is described from a surface science point of view. Particulars are given to SAMs on titanium concerning surface morphology, chemical composition and affinity of specific head group for Ti surfaces (silanes, siloxane, phosphonates and phosphates). Preparation, coating methodologies, limitations and techniques used for the characterization of SAMs are reported. For their physicochemical characteristics and micro-nano scale features some perspectives of using SAMs in biomedical application are outlined.

Maxillo-mandibular rehabilitations with very early osteointegrated dental implants for severe hypodontia and anodontia related to ectodermal dysplasia

The ectodermal dysplasias are rare diseases with hypodontia, hypotrichosis and hypohidrosis. The subject's life is considerably constrained and this from an early age, with major difficulties for the integration and acceptance of conventional prosthetic occlusal rehabilitation. The use of implants is an integral part of early treatment, in the regions of stable growth, that is to say symphysis. In two childs of 5 and 6 years we have made implant-borne prosthetic rehabilitation in the maxilla and the mandible. Aesthetic and social evaluation were positive. We have restored the normal oro-facial functions for the correct development of skeletal bases. They acted as an external fixator intraoral, stimulating the growth by the function. Our question was: can we leave a child throughout his childhood and adolescence with a not suitable removable prosthesis, under the pretext of growth unfinished?

Biomimetic AgNPs@antimicrobial peptide/silk fibroin coating for infection-trigger antibacterial capability and enhanced osseointegration

Endowing implant surfaces with combined antibacterial and osteogenic properties by drug-loaded coatings has made great strides,but how to achieve the combined excellence of infection-triggered bactericidal and in vivo-proven osteogenic activities without causing bacterial resistance still remains a formidable challenge.Herein,antimicrobial peptides(AMPs)with osteogenic fragments were designed and complexed on the surface of silver nanoparticle(AgNP)through hydrogen bonding,and the collagen structure-bionic silk fibroin(SF)was applied to carry AgNPs@AMPs to achieve infection-triggered antibacterial and osteointegration.As verified by TEM,AMPs contributed to the dispersion and size-regulation of AgNPs,with a particle size of about 20 nm,and a clear protein corona structure was observed on the particle surface.The release curve of silver ion displayed that the SF-based coating owned sensitive pH-responsive properties.In the antibacterial test against S.aureus for up to 21 days,the antibacterial rate had always remained above 99%.Meanwhile,the underlying mechanism was revealed,originating from the destruction of the bacterial cell membranes and ROS generation.The SF-based coating was conducive to the adhesion,diffusion,and proliferation of bone marrow stem cells(BMSCs)on the surface,and promoted the expression of osteogenic genes and collagen secretion.The in vivo implantation results showed that compared with the untreated Ti implants,SF-based coating enhanced osseointegration at week 4 and 8.Overall,the AgNPs@AMPs-loaded SF-based coating presented the ability to synergistically inhibit bacteria and promote osseointegration,possessing tremendous potential application prospects in bone defects and related-infection treatments.

Biofunctionalization of metallic implants by calcium phosphate coatings

Metallic materials have been extensively applied in clinical practice due to their unique mechanical properties and durability.Recent years have witnessed broad interests and advances on surface functionalization of metallic implants for high-performance biofunctions.Calcium phosphates(CaPs)are the major inorganic component of bone tissues,and thus owning inherent biocompatibility and osseointegration properties.As such,they have been widely used in clinical orthopedics and dentistry.The new emergence of surface functionalization on metallic implants with CaP coatings shows promise for a combination of mechanical properties from metals and various biofunctions from CaPs.This review provides a brief summary of state-of-art of surface biofunctionalization on implantable metals by CaP coatings.We first glance over different types of CaPs with their coating methods and in vitro and in vivo performances,and then give insight into the representative biofunctions,i.e.osteointegration,corrosion resistance and biodegradation control,and antibacterial property,provided by CaP coatings for metallic implant materials.

Gaseous sulfur trioxide induced controllable sulfonation promoting biomineralization and osseointegration of polyetheretherketone implants

Fabricating a desired porous structure on the surface of biomedical polyetheretherketone(PEEK)implants for enhancing biological functions is crucial and difficult due to its inherent chemical inertness.In this study,a porous surface of PEEK implants was fabricated by controllable sulfonation using gaseous sulfur trioxide(SO3)for different time(5,15,30,60 and 90 min).Micro-topological structure was generated on the surface of sulfonated PEEK implants preserving original mechanical properties.The protein absorption capacity and apatite forming ability was thus improved by the morphological and elemental change with higher degree of sulfonation.In combination of the appropriate micromorphology and bioactive sulfonate components,the cell adhesion,migration,proliferation and extracellular matrix secretion were obviously enhanced by the SPEEK-15 samples which were sulfonated for 15 min.Finding from this study revealed that controllable sulfonation by gaseous SO3 would be an extraordinarily strategy for improving osseointegration of PEEK implants by adjusting the microstructure and chemical composition while maintaining excellent mechanical properties.

Porous tantalum structure integrated on Ti6Al4V base by Laser Powder Bed Fusion for enhanced bony-ingrowth implants:In vitro and in vivo validation

Despite the widespread application of Ti6Al4V and tantalum(Ta)in orthopedics,bioinertia and high cost limit their further applicability,respectively,and tremendous efforts have been made on the Ti6Al4V-Ta alloy and Ta coating to address these drawbacks.However,the scaffolds obtained are unsatisfactory.In this study,novel high-interface-strength Ti6Al4V-based porous Ta scaffolds were successfully manufactured using Laser Powder Bed Fusion for the first time,in which porous Ta was directly manufactured on a solid Ti6Al4V substrate.Mechanical testing revealed that the novel scaffolds were biomechanically compatible,and the interfacial bonding strength was as high as 447.5 MPa.In vitro biocompatibility assay,using rat bone marrow mesenchymal stem cells(r-BMSCs),indicated that the novel scaffolds were biocompatible.Alkaline phosphatase and mineralized nodule determination demonstrated that the scaffolds favored the osteogenic differentiation of r-BMSCs.Moreover,scaffolds were implanted into rabbits with femur bone defects,and imaging and histological evaluation identified considerable new bone formation and bone ingrowth,suggesting that the scaffolds were well integrated with the host bone.Overall,these results demonstrated good mechanical compatibility,biocompatibility,and osteointegration performance of the novel Ti6Al4V-based porous Ta scaffold,which possesses great potential for orthopedic clinical applications.

Ultrafine-grained Nb-Cu immiscible alloy implants for hard tissue repair:Fabrication,characterization,and in vitro and in vivo evaluation

The biocompatible metallic implants with strong osteointegration often lack the ability of anti-infection.The biocompatible niobium(Nb)containing the antibacterial copper(Cu),the obtained Nb-Cu alloy,could be a potential candidate to solve this issue.To test this hypothesis,ultrafine-grained Nb-Cu immiscible alloys were fabricated via mechanical alloying and spark plasma sintering.The aim of this study was to investigate the microstructure,mechanical properties,magnetic susceptibility,corrosion behavior,ion release,and the bactericidal activity,biocompatibility and osteogenic potential of the Nb-Cu alloys in vitro and their osteogenesis and osteointegration ability in vivo with a comparison with pure Nb.The rat cranial defect model and the bone screws insertion in rabbit femoral bone were used to evaluate the osteogenesis and osteointegration ability,respectively.The results showed that after the addition of 3 wt.%of Cu,the compressive strength was significantly improved from 1.57 GPa to 2.21 GPa and the magnetic susceptibility slightly decreased.The Nb-3 wt.%Cu(Nb-3Cu)alloy exhibited higher corrosion resistance than pure Nb in Hank’s solution and strong bactericidal activity against both E.coli and S.aureus.In vitro,the Nb-3Cu alloy showed comparable biocompatibility with pure Nb.The addition of 3 wt.%Cu also significantly enhanced the expression of osteogenesis-related genes(RUNX2,ALP,COLA1 and OCN)of pre-osteoblasts.In vivo,the Nb-3Cu alloy promoted bone regeneration at the defect sites and showed enhanced osteointegration after 12 weeks of implantation.Such a good combination of high mechanical strength and corrosion resistance,strong antibacterial activity and improved osteogenesis and osseointegration ability enables the present Nb-3Cu alloy a promising candidate for heavy load-bearing hard tissue repair.

Bioadaptive Nanorod Topography of Titanium Surface to Control Cell Behaviors and Osteogenic Differentiation of Preosteoblast Cells

Titanium （Ti） nanorods fabricated using selective corrosion of Ti substrate by anodic technology show better biocompatibility with pre-osteoblast cells. The current study investigated the response of the murine pre-osteoblast cell MCST3-E1 on Ti nanorod topography and untreated Ti surfaces by means of examination of the morphology and osteogenic differentiation responsible for the pre-osteoblast reaction. The morphology of MCST3-E1 cells was observed using scanning electron microscopy, and alkaline phosphatase （ALP） activity was measured using a colorimetric assay after incubation for 7, 14, and 21 days. The expression of three osteogenic differentiation markers including ALP, osteocalcin （OCN）, and collagen type 1A1 （COL1A1） and two transcription factors including runt related transcription factor 2 （Runx2） and osterix （Osx） at different time points was detected using real-time polymerase chain reaction analysis in both groups. Osx was used to confirm the protein level. The results showed that Ti nanorod surfaces provided prolonged higher levels of ALP activity compared with unmodified Ti surface on the 14th and 21st days. Gene expression analysis of ALP, OCN, and COL1A1 showed significant upregulation with modified nanorod topography after incubation for 14 and 21 days. Osteogenic transcription factors of Runx2 and Osx exhibited changes consistent with the osteogenic differentiation markers, and this may contribute to the persistently active differentiation of MC3T3-E1 cells in the Ti nanorod group. These results demonstrated that the current nanostructured surface may be considered bioadaptive topography to control cellular behaviors and osteoblast differentiation. The in vivo performance and applicability are further required to investigate osseointegration between implant and host bone in the early stages for prevention of aseptic implant loosening.