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.

Additive manufacturing technologies of porous metal implants

Biomedical metal materials with good corrosion resistance and mechanical properties are widely used in orthopedic surgery and dental implant materials,but they can easily cause stress shielding due to the significant difference in elastic modulus between the implant and human bones.The elastic modulus of porous metals is lower than that of dense metals.Therefore,it is possible to adjust the pore parameters to make the elastic modulus of porous metals match or be comparable with that of the bone tissue.At the same time,the open porous metals with pores connected to each other could provide the structural condition for bone ingrowth,which is helpful in strengthening the biological combination of bone tissue with the implants.Therefore,the preparation technologies of porous metal implants and related research have been drawing more and more attention due to the excellent features of porous metals.Selective laser melting(SLM)and electron beam melting technology(EBM)are important research fields of additive manufacturing.They have the advantages of directly forming arbitrarily complex shaped metal parts which are suitable for the preparation of porous metal implants with complex shape and fine structure.As new manufacturing technologies,the applications of SLM and EBM for porous metal implants have just begun.This paper aims to understand the technology status of SLM and EBM,the research progress of porous metal implants preparation by using SLM and EBM,and the biological compatibility of the materials,individual design and manufacturing requirements.The existing problems and future research directions for porous metal implants prepared by SLM and EBM methods are discussed in the last paragraph.

The Tissue Reactions and Changes of a Surface of Various Metal Implants after Their Introduction in a Bone Tissue in Experiment

Screw metal implants (3S, Israel) with rough or smooth polished surface were introduced in a tibial proximal condyle of not purebred rabbits. The condition of surrounding tissues in 2 and 6 months after implantation was compared by light microscopy and X-ray methods. Within 6 months after operation the considerable distinctions of radiological and morphological data were revealed not. 2 months later after introduction of implants with a rough surface the effort enclosed for its twisting is, much more, than for removal of the polished product. However, stability of fixing of implants was practically made even at 6 months. On remote rough implants there is a set of tissue scraps whereas on products with a smooth surface the tissue remains were much less. Surrounding tissues strongly join a rough surface, grow into cavities, and during removal of such products there is a considerable trauma of tissues round an implantation place. Smooth implants have the smaller area of contact with organism tissues, they are fixed due to bicortical implantation, during removal easily get out and don’t break off surrounding tissues. The signs of inflammation and formation of merged multinuclear macrophages were not found at all cases, which give evidence to the inertness of material of the mentioned articles for living organism. In some observations however and by implantation of the rough article and by introduction of polished implants, metal particles were found, but after use of the foreign body with grit-blasted treatment of surface metal was found more frequently, and its fragments had larger volume.

Interaction pathways of implant metal localized corrosion and macrophage inflammatory reactions

Macrophages play a central role in immunological responses to metallic species associated with the localized corrosion of metallic implants,and mediating in peri-implant inflammations.Herein,the pathways of localized corrosion-macrophage interactions were systematically investigated on 316L stainless steel(SS)implant metals.Electrochemical monitoring under macrophage-mediated inflammatory conditions showed a decreased pitting corrosion resistance of 316L SSs in the presence of RAW264.7 cells as the cells would disrupt biomolecule adsorbed layer on the metal surface.The pitting potentials were furtherly decreased when the RAW264.7 cells were induced to the M1 pro-inflammatory phenotype by the addition of lipopolysaccharide(LPS),and pitting corrosion preferentially initiated at the peripheries of macrophages.The overproduction of aggressive ROS under inflammatory conditions would accelerate the localized corrosion of 316L SS around macrophages.Under pitting corrosion condition,the viability and pro-inflammatory polarization of RAW264.7 cells were region-dependent,lower viability and more remarkable morphology transformation of macrophages in the pitting corrosion region than the pitting-free region.The pitting corrosion of 316L SS induced high expression of CD86,TNF-α,IL-6 and high level of intracellular ROS in macrophages.Uneven release of metallic species(Fe^(2+),Cr^(3+),Ni^(2+),etc)and uneven distribution of surface overpotential stimulated macrophage inflammatory responses near the corrosion pits.A synergetic effect of localized corrosion and macrophages was revealed,which could furtherly promote localized corrosion of 316L SS and macrophage inflammatory reactions.Our results provided direct evidence of corrosion-macrophage interaction in metallic implants and disclosed the pathways of this mutual stimulation effect.

Design,fabrication,and structural safety validation of 3D-printable biporous bone augments

The use of commercial products such as a cup and liner for total hip arthroplasty for patients with severe bone defects has a high probability of failure.In these patients the cup alone cannot cover the bone defect,and thus,an additional augment or cage is required.In this study,we designed three-dimensional(3D)printable bone augments as an alternative to surgeries using reinforcement cages.Thirty-five sharp-edged bone augments of various sizes were 3D printed.A biporous structure was designed to reduce the weight of the augment and to facilitate bone ingrowth.Two types of frames were used to prevent damage to the augment’s porous structure and maintain its stability during printing.Furthermore,two types of holes were provided for easy augment fixation at various angles.Fatigue tests were performed on a combination of worst-case sizes derived using finite element analysis.The test results confirmed the structural stability of the specimens at a load of 5340 N.Although the porosity of the specimens was measured to be 63.70%,it cannot be said that the porous nature was uniformly distributed because porosity tests were performed locally and randomly.In summary,3D-printable biporous bone augments capable of bonding from various angles and bidirectionally through angulation and bottom-plane screw holes are proposed.The mechanical results with bone augments indicate good structural safety in patients.However,further research is necessary to study the clinical applications of the proposed bone augment.

Dopant-Tunable Ultrathin Transparent Conductive Oxides for Efficient Energy Conversion Devices

Ultrathin film-based transparent conductive oxides(TCOs)with a broad work function(WF)tunability are highly demanded for e cient energy conversion devices.However,reducing the film thickness below 50 nm is limited due to rapidly increasing resistance;furthermore,introducing dopants into TCOs such as indium tin oxide(ITO)to reduce the resistance decreases the transparency due to a trade-o between the two quantities.Herein,we demonstrate dopant-tunable ultrathin(≤50 nm)TCOs fabricated via electric field-driven metal implantation(m-TCOs;m=Ni,Ag,and Cu)without com-promising their innate electrical and optical properties.The m-TCOs exhibit a broad WF variation(0.97 eV),high transmittance in the UV to visible range(89–93%at 365 nm),and low sheet resistance(30–60Ωcm-2).Experimental and theoretical analyses show that interstitial metal atoms mainly a ect the change in the WF without substantial losses in optical transparency.The m-ITOs are employed as anode or cathode electrodes for organic light-emitting diodes(LEDs),inorganic UV LEDs,and organic photovoltaics for their universal use,leading to outstanding performances,even without hole injection layer for OLED through the WF-tailored Ni-ITO.These results verify the proposed m-TCOs enable e ective carrier transport and light extraction beyond the limits of traditional TCOs.

Hydrogels of Chemically Cross-linked and Organ-metallic Complexed Interpenetrating PEG Networks

The aim of the present work was to prepare a well-defined hydrogel of chemically cross-linked and organ-metallic complexed interpenetrating PEG networks. The hydrogel was synthesized via the reaction of copper（I）- catalyzed 1,3-dipolar azide-alkyne cycloaddition（CuA AC） with poly（ethylene glycol）-dopamine（PEG-DA）（“Click Chemistry”） followed by complexation with Fe-（3＋） ions to crosslink the polymeric network. The chemical composition and morphology of the resulting hydrogels were characterized by Fourier transform infrared spectroscopy（FTIR）, -1H-NMR and scanning electron microscopy（SEM）. Swelling ratio, mechanical strength, conductivity, and degradation behaviors of the hydrogels were also studied. The effect of the polymer chain length on properties of hydrogels was explored. The compressive strength of hydrogels could reach as high as 13.1 MPa with a conductivity of 2.2 × 10^-5 S·cm^-1. The hydrogels also exhibited excellent thermal stability even at a temperature of 300 °C, whereas degradation of the hydrogel after 7 weeks was observed under a physiological condition. In addition, the hydrogel exhibited a good biocompatibility based on its in vivo performance through an in vivo subcutaneous implantation model. No inflammation and no obvious abnormality of the surrounding tissue were observed when the hydrogel was subcutaneously implanted for 2 weeks. This work is a step towards creating a new pathway to synthesize hydrogels of interpenetrating networks which could be of important applications in the future research.

Additively manufactured metallic biomaterials

Metal additive manufacturing(AM)has led to an evolution in the design and fabrication of hard tissue substitutes,enabling personalized implants to address each patient’s specific needs.In addition,internal pore architectures integrated within additively manufactured scaffolds,have provided an opportunity to further develop and engineer functional implants for better tissue integration,and long-term durability.In this review,the latest advances in different aspects of the design and manufacturing of additively manufactured metallic biomaterials are highlighted.After introducing metal AM processes,biocompatible metals adapted for integration with AM machines are presented.Then,we elaborate on the tools and approaches undertaken for the design of porous scaffold with engineered internal architecture including,topology optimization techniques,as well as unit cell patterns based on lattice networks,and triply periodic minimal surface.Here,the new possibilities brought by the functionally gradient porous structures to meet the conflicting scaffold design requirements are thoroughly discussed.Subsequently,the design constraints and physical characteristics of the additively manufactured constructs are reviewed in terms of input parameters such as design features and AM processing parameters.We assess the proposed applications of additively manufactured implants for regeneration of different tissue types and the efforts made towards their clinical translation.Finally,we conclude the review with the emerging directions and perspectives for further development of AM in the medical industry.

Frontiers of 3D Printing/Additive Manufacturing: from Human Organs to Aircraft Fabrication

It has been more than three decades since stereolithography began to emerge in various forms of additive manufacturing and 3D printing. Today these technologies are proliferating worldwide in various forms of advanced manufacturing. The largest segment of the 3D printing market today involves various polymer component fabrications, particularly complex structures not attainable by other manufacturing methods.Conventional printer head systems have also been adapted to selectively print various speciated human cells and special molecules in attempts to construct human organs, beginning with skin and various tissue patches. These efforts are discussed along with metal and alloy fabrication of a variety of implant and bone replacement components by creating powder layers, which are selectively melted into complex forms（such as foams and other open-cellular structures） using laser and electron beams directed by CAD software. Efforts to create a ＂living implant＂ by bone ingrowth and eventual vascularization within these implants will be discussed briefly. Novel printer heads for direct metal droplet deposition as in other 3D printing systems are briefly described since these concepts will allow for the eventual fabrication of very large and complex products, including automotive and aerospace structures and components.