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.

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.

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.

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.

Evaluation of titanium dental implants after early failure of osseointegration by means of X-ray photoelectron spectoscopy, electron microscopy and histological studies

In this work, we analysed 56 clinically failed and retrieved implants by means of scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and histological studies. The surface contamination was compared to that of unused control implants and with that of the same implants after cleaning in a basic medium. The surfaces of the unused implants presented considerable contamination. In particular, high levels of carbon were detected. The nature of this C was elucidated by XPS analysis of the lubricant used in the machining process. The same contamination was observed in the retrieved implants. Histological studies were carried out by means of light microscopy. Fibrosis and granulomatous lesions were detected in the tissues. XPS analysis indicated the presence of traces of other elements (Na, Ca, Zn, S, F, etc.) that were not related to impurities in cpTi. We examined a cleaning process in a basic medium that eliminates the organic components of the implant surfaces. The cleaned implants were implanted in the patients and the results were excellent. None of the implants failed in following 7 months.

Surface modification of titanium implant for repairing/improving microenvironment of bone injury and promoting osseointegration

Bone injury and implantation operation are often accompanied by microenvironment damage of bone tis-sue,which seriously affects the process of osseointegration of implants,especially for titanium(Ti)-based bioinert materials.Thus,repairing or improving the microenvironment of damaged bone tissue is of great significance for bone rescue,reconstruction,and regeneration,which is still a major medical challenge.Oxidative stress(OS)and oxygen(O_(2))deficiency are considered to be specific physiological signals of the bone-injury microenvironment.From the above background,a coating consisting of manganese dioxide(MnO_(2))nanoenzyme and strontium(Sr)ions was fabricated on the surface of the Ti implant via a one-step hydrothermal treatment.MnO_(2) nanoenzyme presented in the coating alleviated OS and O_(2) deficiency at the injury site by catalyzing the decomposition of abundant endogenous H_(2)O_(2) around the modified Ti implants into O_(2).In addition,Sr ions were released from the surface of the implant at a certain rate in a body-fluid environment,further promoting the adhesion,growth,and osteogenic differentiation of mesenchymal stem cells.More importantly,a Sprague Dawley rat femur model demonstrated that the modified Ti implant showed significant potential to accelerate bone tissue reconstruction in vivo.In sum-mary,the present system provides a new idea for the treatment of bone injury and the development of new orthopedic implants.

A biomimetic gradient porous cage with a micro-structure for enhancing mechanical properties and accelerating osseointegration in spinal fusion

Objectives:Spinal fusion is a widely employed treatment of patients with degenerative disc disease,in which a cage is used to replace the disc for spinal fusion.But it often fails for insufficient mechanical strength and poor osseointegration.Here,we designed a polyether-ether-ketone(PEEK)/tantalum(Ta)composite cage with a biomimetic gradient porous micro-structure,simultaneously enhancing mechanical properties and accelerating osseointegration in spinal fusion.Materials and methods:In the study,based on the mechanical performances of PEEK and osteogenic potential of Ta,and the three-dimensional(3D)structures of cuttlebone and vertebra,the cages were respectively 3D printed by pure PEEK,PEEK with 5 wt%Ta(PEEK/Ta-5),PEEK with 10 wt%Ta(PEEK/Ta-10)and PEEK with 15 wt%Ta(PEEK/Ta-15),then verifiedin vitroand in sheep cervical fusion model systematically.Results:Vertebral Gyroid structure PEEK/Ta-15 cage exhibited superior mechanical properties than Cuttlebone-like structure PEEK/Ta-15 cage,closer to the cervical vertebra.Furthermore,PEEK/Ta-15 cage with higher Ta microparticles in PEEK provided a biomimetic gradient porous micro-structure with higher surface energy,guiding cell biological behavior,promoting new bone penetration,and accelerating osseointegrationin vivo.Conclusion:In conclusion,the study designed a biomimetic gradient porous cage with a micro-structure for enhancing mechanical properties,accelerating osseointegration and forming an anatomical lock in the fusion segment through composites,mechanical efficiency,surface extension,and pores.

3D-printed surface promoting osteogenic differentiation and angiogenetic factor expression of BMSCs on Ti6Al4V implants and early osseointegration in vivo

Three-dimensional-printed(3 D-P) titanium implants display many advantages, such as design flexibility,higher efficiency, the capability to easily construct complex or customized structures, etc., and is believed to potentially replace traditional implants. However, the biological performance of the 3 D-P titanium surface has not been investigated systematically. Herein, we analyzed the surface characteristics of 3 D-P Ti6 Al4 V implants and evaluated the biological responses of bone marrow derived mesenchymal stromal cells(BMSCs) to the 3 D-P surface in vitro. Moreover, after implantation into the rat femoral condyle for3 and 6 weeks, the osseointegration performance was evaluated. The results showed the 3 D-P Ti6 Al4 V implant presented distinct fluctuant macroscale rough surface and relatively better hydrophilicity which enhanced the adhesion, proliferation, osteogenic differentiation and angiogenetic factor expression of BMSCs. Moreover, the in vivo osseointegration performance was also better than that of the control group at the early stage. The present study suggested the 3 D-P titanium alloy is a promising candidate to be used as implant material.

Strategies for creating living, additively manufactured, open-cellular metal and alloy implants by promoting osseointegration,osteoinduction and vascularization: An overview

Additive manufacturing of porous, open-cellular metal or alloy implants, fabricated by laser or electron beam melting of a powder bed, is briefly reviewed in relation to optimizing biomechanical compatibility by assuring elastic(Young's) modulus matching of proximate bone, along with corresponding pore sizes assuring osseointegration and vasculature development and migration. In addition, associated, requisite compressive and fatigue strengths for such implants are described. Strategies for optimizing osteoblast(bone cell) development and osteoinduction as well as vascularization of tissue in 3 D scaffolds and tissue engineering constructs for bone repair are reviewed in relation to the biology of osteogenesis and neovascularization in bone, and the role of associated growth factors, bone morphogenic proteins, signaling molecules and the like. Prospects for infusing hydrogel/collagen matrices containing these cellular and protein components or surgically extracted intramedullary(bone marrow) concentrate/aspirate containing these biological and cell components into porous implants are discussed, as strategies for creating living implants, which over the long term would act as metal or alloy scaffolds.

A microporous surface containing Si3N4/Ta microparticles of PEKK exhibits both antibacterial and osteogenic activity for inducing cellular response and improving osseointegration

As an implantable biomaterial,polyetherketoneketone(PEKK)exhibits good mechanical strength but it is biologically inert while tantalum(Ta)possesses outstanding osteogenic bioactivity but has a high density and elastic modulus.Also,silicon nitride(SN)has osteogenic and antibacterial activity.In this study,a microporous surface containing both SN and Ta microparticles on PEKK(STP)exhibiting excellent osteogenic and antibacterial activity was created by sulfonation.Compared with sulfonated PEKK(SPK)without microparticles,the surface properties(roughness,surface energy,hydrophilicity and protein adsorption)of STP significantly increased due to the SN and Ta particles presence on the microporous surface.In addition,STP also exhibited outstanding antibacterial activity,which inhibited bacterial growth in vitro and prevented bacterial infection in vivo because of the presence of SN particles.Moreover,the microporous surface of STP containing both SN and Ta particles remarkably induced response(e.g.,proliferation and differentiation)of rat bone mesenchymal stem(rBMS)cells in vitro.Furthermore,STP significantly improved new bone regeneration and osseointegration in vivo.Regarding the induction of cellular response in vitro and improvement of osseointegration in vivo,the microporous surface containing Ta was better than the surface with SN particles.In conclusion,STP with optimized surface properties activated cellular responses in vitro,enhanced osseointegration and prevented infection in vivo.Therefore,STP possessed the dual biofunctions of excellent osteogenic and antibacterial activity,showing great potential as a bone substitute.

Implantable PEKK/tantalum microparticles composite with improved surface performances for regulating cell behaviors,promoting bone formation and osseointegration

Polyetherketoneketone(PEKK)exhibits admirable biocompatibility and mechanical performances but bioinert while tantalum(Ta)possesses excellent osteogenesis and osseointegration but high elastic modulus and density,and processing is too difficult and expensive.In the present study,combining of the advantages of both PEKK and Ta,implantable composites of PEKK/Ta were fabricated by blending PEKK with Ta microparticles of 20 v%(PT20)and 40 v%(PT40)content.In comparison with PT20 and PEKK,the surface hydrophilicity,surface energy,roughness and proteins adsorption as well as mechanical performances of PT40 significantly increased because of the higher Ta particles content in PEKK.Furthermore,PT40 exhibited the mechanical performances(e.g.,compressive strength and modulus of elasticity)close to the cortical bone of human.Compared with PT20 and PEKK,PT40 with higher Ta content remarkably enhanced the responses(including adhesion,proliferation and osteogenic differentiation)of MC3T3-E1 cells in vitro.Moreover,PT40 markedly improved bone formation as well as osseointegration in vivo.In short,incorporation of Ta microparticles into PEKK created implantable composites with improved surface performances,which played key roles in stimulating cell responses/bone formation as well as promoting osseointegration.PT40 might have great potential for bear-loading bone substitute.

The influence of mechanical loading on osseointegration:an animal study

Osseointegration of implant provides a stable support for the prosthesis under functional loads.The timing of loading is a critical parameter that can govern the success of the osseointegration of implant.However,it is not clear whether the early loading can affect the success of osseointegration,or whether the no-loading healing period can be shortened.This paper presents an animal study conducted to investigate how external loads influence the osseointegration at the initial stage of healing.Titanium implants were inserted into the goat tibia laterally,and different axial loadings were applied to the im-plants in 4 weeks after surgery.After the 2 weeks period of early loading,animals were sacrificed and the tibia bones with the implants were cut off from the bodies.Then mechanical test was employed to find out the differences in the pull-out force,and shear strength at the bone-implant interface between the non-loaded and the loaded implants.The implant-bone interfaces were analyzed by histomor-phometric method,SEM(scanning electron micrograph) and EDS(energy density spectrum).The re-sults indicated that the bone-implant interface did not well integrate 4 weeks after surgery,and the fi-brous tissue could be found at the interfaces of the specimens without loadings.While the results of loaded specimens with 10 N axial force showed that that parts of the interface were well integrated,indicating that the early mild loading may play a positive role in the process of the osseointegration.The results support that a certain range of external loading would influence the process of osseointe-gration,and appropriate mechanical loading can be applied to shorten the osseointegration period after surgery.

Fluorescence microscopic analysis of bone osseointegration of strontium-substituted hydroxyapatite implants

The purpose of this study was to analyze the effect of strontium-substituted hydroxyapatite (Sr-HA) on bone osseointegration of the implants using fluorescence microscopy. We allocated 20 implants to two groups: Sr-HA group and HA group. Electrochemically deposited HA and Sr-HA coatings were applied onto the implants separately. All the implants were inserted into femur bone of rabbits. Oxytetracycline hydrochloride, alizarin-complexon, and calcein green were respectively administered 7, 28, and 46 d after the implantation. After eight weeks, femurs were retrieved and prepared for the fluorescence microscopy observation. We analyzed the bone mineral apposition rates (MARs), bone area ratios (BARs), and bone to implant contact (BIC) of the two groups. Fluorescence microscopic observation showed that all groups exhibited extensive early peri-implant bone formation. The MAR of the Sr-HA group was greater than that for pure HA from 7 to 28 d after implantation, but no significant difference was found at later stage. And the BIC showed difference at 7 and 28 d compared with pure HA. We concluded that Sr-HA coating can improve the bone osseointegration of the implant in the early stage compared with the HA coating.

Nano-needle strontium-substituted apatite coating enhances osteoporotic osseointegration through promoting osteogenesis and inhibiting osteoclastogenesis

Implant loosening remains a major clinical challenge for osteoporotic patients.This is because osteoclastic bone resorption rate is higher than osteoblastic bone formation rate in the case of osteoporosis,which results in poor bone repair.Strontium(Sr)has been widely accepted as an anti-osteoporosis element.In this study,we fabricated a series of apatite and Sr-substituted apatite coatings via electrochemical deposition under different acidic conditions.The results showed that Ca and Sr exhibited different mineralization behaviors.The main mineralization products for Ca were CaHPO4⋅2H2O and Ca3(PO4)2 with the structure changed from porous to spherical as the pH values increased.The main mineralization products for Sr were SrHPO4 and Sr5(PO4)3OH with the structure changed from flake to needle as the pH values increased.The in vitro experiment demonstrated that coatings fabricated at high pH condition with the presence of Sr were favorable to MSCs adhesion,spreading,proliferation,and osteogenic differentiation.In addition,Sr-substituted apatite coatings could evidently inhibit osteoclast differentiation and fusion.Moreover,the in vivo study indicated that nano-needle like Sr-substituted apatite coating could suppress osteoclastic activity,improve new bone formation,and enhance bone-implant integration.This study provided a new theoretical guidance for implant coating design and the fabricated Sr-substituted coating might have potential applications for osteoporotic patients.

Calcium phosphate-based materials regulate osteoclast-mediated osseointegration

Calcium phosphate-based materials(CaP)have been widely used as bone graft substitutes with a decent osseointegration.However,the mechanism whereby cells function and repair the bone defect in CaP micro-environment is still elusive.The aim of this study is to find the mechanism how osteoclast behaviors mediate bone healing with CaP scaffolds.Recent reports show that behaviors of osteoclast are closely related with osteogenesis,thus we make a hypothesis that active osteoclast behaviors induced by CaP facilitate bone healing.Here,we found a new mechanism that CaP can regulate osteoclast-mediated osseointegration.Calcium phosphate cement(CPC)is selected as a representative CaP.We demonstrate that the osteoclast-mediated osseointegration can be strongly modulated by the stimulation with CaP.An appropriate Ca/P ratio in CaP can effectively promote the RANKL-RANK binding and evoke more activated NF-κB signaling transduction,which results in vigorous osteoclast differentiation.We observe significant improvement of bone healing in vivo,owing to the active coupling effect of osteoclasts.What is more noteworthy is that the phosphate ions released from CaP can be a pivotal role regulating osteoclast activity by changing Ca/P ratio readily in materials.These studies suggest the potential of harnessing osteoclast-mediated osteogenesis in order to develop a materials-manipulated approach for improving osseointegration.

Powder metallurgical Ti-Mg metal-metal composites facilitate osteoconduction and osseointegration for orthopedic application

In this work,TieMg metal-metal composites(MMCs)were successfully fabricated by spark plasma sintering(SPS).In vitro,the proliferation and differentiation of SaOS-2 cells in response to TieMg metal-metal composites(MMCs)were investigated.In vivo,a rat model with femur condyle defect was employed,and TieMg MMCs implants were embedded into the femur condyles.Results showed that TieMg MMCs exhibited enhanced cytocompatibility to SaOS-2 cells than pure Ti.The micro-computed tomography(Micro-CT)results showed that the volume of bone trabecula was significantly more abundant around TieMg implants than around Ti implants,indicating that more active new-bone formed around TieMg MMCs implants.Hematoxylin-eosin(H&E)staining analysis revealed significantly greater osteointegration around TieMg implants than that around Ti implants.

Evaluation of channel-like porous-structured titanium in mechanical properties and osseointegration

The porous titanium with a channel-like pore structure fabricated by infiltration casting followed by selectively dissolving the precursor woven three dimensional(3D)structure technique was comprehensively investigated by means of mechanical tests,in vitro and in vivo evaluation.Such porous structure exhibited superiority in compressive,tensile strength and osseointegration.At 40%porosity,the average compressive and tensile strength reached about 145MPa and 85 MPa,which was superior to that of other porous titanium,e.g.,Selective Laser Melting or powder sintered ones,and was comparable to that of the human cortical bone.Without any bioactive surface treatment,this porous titanium exhibited good cell adhesion,rapid cell proliferation and excellent osseointegration.Based on the study,the 0.4mm pore size resulted in the most rapid cell proliferation and the maximal BV/TV ratio and trabecular bone number of the new bone that ingrew into the porous titanium.To balance the excellent osseointegration and adequate mechanical properties,the optimal structural parameters were 0.4mmpore size with 40%porosity.This porous titanium is very promising for orthopedic applications where compressive and tensile load-bearing is extremely important.

Hierarchical Micropore/Nanorod Apatite Hybrids In-Situ Grown from 3-D Printed Macroporous Ti6Al4V Implants with Improved Bioactivity and Osseointegration

The advent of three-dimensional(3-D) printed technique provides great possibility in the fabrication of customized porous titanium(Ti) implant. However, the bioinert property of the printed Ti poses an outstanding problem. Hybrid micro-arc oxidation and hydrothermal(MAO–HT) treatment on porous metals is able to produce multi-scaled hierarchical orthopedic implant, showing great potential for surface modification of 3-D printed implant. In this study, cylindrical porous Ti6Al4V(Ti64) scaffolds with pore size of 640 μm, porosity of 73% were 3-D printed by electron beam melting process, and their surfaces were left untreated or treated by a combined MAO–HT procedure. In vitro bioactivity was tested by immersion in simulated body fluid for different time points. Then, 12 scaffolds in each group were implanted into the femoral condyles of New Zealand rabbit for 8 weeks. Osseointegration was evaluated by qualitative and quantitative histological analysis, and the bone ingrowth features were probed by sequential fluorescent labeling at 3 and 6 weeks post-surgery. Following the MAO–HT treatment, the porous Ti64 scaffold was endowed with multi-scaled micro/nano-topographies and high amounts of Ca P on its surface.The treated scaffold exhibited drastically enhanced apatite forming ability compared with the untreated one. In vivo test revealed significantly that a higher amount of bone ingrowth and bone implant contact at the treated scaffold. The 2 types of scaffolds had different patterns of bone ingrowth: the treated scaffold exhibited a pattern of contact osteogenesis, by which bone formed directly on the treated implant surface, whereas bone formed distal to the implant surface of the untreated scaffold. MAO–HT treatment can significantly enhance the in vitro apatite-inducing ability and in vivo osseointegration capacity of 3-D porous Ti64 scaffold and may provide as a viable approach for the fabrication of bioactive 3-D printed porous implant for orthopedic applications.

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 N_(2) plasma immersion ion implantation and subsequent immersion in IL-4 solution.Dominant release of IL-4 together with ALN and Ca^(2+) 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 Ca^(2+) 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.

Surface treatment of 3D printed porous Ti6Al4V implants by ultraviolet photofunctionalization for improved osseointegration

Three-dimensional(3D)-printed porous Ti6Al4V implants play an important role in the reconstruction of bone defects.However,its osseointegration capacity needs to be further improved,and related methods are inadequate,especially lacking customized surface treatment technology.Consequently,we aimed to design an omnidirectional radiator based on ultraviolet(UV)photofunctionalization for the surface treatment of 3D-printed porous Ti6Al4V implants,and studied its osseointegration promotion effects in vitro and in vivo,while elucidating related mechanisms.Following UV treatment,the porous Ti6Al4V scaffolds exhibited significantly improved hydrophilicity,cytocompatibility,and alkaline phosphatase activity,while preserving their original mechanical properties.The increased osteointegration strength was further proven using a rabbit condyle defect model in vivo,in which UV treatment exhibited a high efficiency in the osteointegration enhancement of porous Ti6Al4V scaffolds by increasing bone ingrowth(BI),the bone-implant contact ratio(BICR),and the mineralized/osteoid bone ratio.The advantages of UV treatment for 3D-printed porous Ti6Al4V implants using the omnidirectional radiator in the study were as follows:1)it can significantly improve the osseointegration capacity of porous titanium implants despite the blocking out of UV rays by the porous structure;2)it can evenly treat the surface of porous implants while preserving their original topography or other morphological features;and 3)it is an easy-to-operate low-cost process,making it worthy of wide clinical application.