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Special Issue "Current Trends in Metallic Biomaterials: From Additive Manufacturing to Bio-functilozation, Infection-Prevention, and Beyond"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (15 July 2018).

Special Issue Editor

Prof. Dr. Amir A. Zadpoor
E-Mail Website
Guest Editor
Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, Delft 2628CD, The Netherlands
Interests: biofabrication and additive bio-manufacturing; mechanobiology; surface bio-functionalization; infection prevention and treatment; metamaterials
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

As one of the first types of biomaterials used in clinical practice, metallic biomaterials have been studied from the early days of biomaterials research. This line of research continues to date as one of the most fertile grounds for breakthrough research, which, not only entices academic interest, but also offers direct solutions for important clinical challenges. The advent of novel manufacturing techniques, such as additive manufacturing and advanced bio-functionalization approaches, has further increased the interest in metallic biomaterials. This Special Issue aims to present a sample of the best research performed in the various areas of metallic biomaterials. The Special Issue covers the metallic biomaterials aimed for application in the various areas of clinical practices including orthopedics, trauma, maxillofacial/craniofacial, and cardiovascular surgeries. The topics of interest include (but are not limited to):

- Additively manufactured metallic biomaterials

- Bio-functionalization including surface treatments and coatings

- Drug delivery systems as applied to metallic biomaterials

- Prevention and treatment of infections associated with metallic implants

- Porous metallic biomaterials

- Improved osseointegration and bone tissue regeneration performance

- Biomaterials-cell interfaces including the effects of (nano-)topography on cell response

- Biodegradable metallic biomaterials and novel manufacturing techniques

- Rational design of metallic biomaterials

- Computational modeling of biomaterials performance using techniques, such as the finite element method.

Assoc. Prof. Amir A. Zadpoor
Guest Editor

Manuscript Submission Information

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Keywords

  • Prostheses
  • metallic biomaterials
  • additive manufacturing
  • bio-functionalities
  • implant-associated infections
  • biodegradable biomaterials
  • drug delivery
  • cell/tissue biomechanics

Published Papers (11 papers)

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Editorial

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Open AccessEditorial
Current Trends in Metallic Orthopedic Biomaterials: From Additive Manufacturing to Bio-Functionalization, Infection Prevention, and Beyond
Int. J. Mol. Sci. 2018, 19(9), 2684; https://doi.org/10.3390/ijms19092684 - 10 Sep 2018
Cited by 5
Abstract
There has been a growing interest in metallic biomaterials during the last five years, as recent developments in additive manufacturing (=3D printing), surface bio-functionalization techniques, infection prevention strategies, biodegradable metallic biomaterials, and composite biomaterials have provided many possibilities to develop biomaterials and medical [...] Read more.
There has been a growing interest in metallic biomaterials during the last five years, as recent developments in additive manufacturing (=3D printing), surface bio-functionalization techniques, infection prevention strategies, biodegradable metallic biomaterials, and composite biomaterials have provided many possibilities to develop biomaterials and medical devices with unprecedented combinations of favorable properties and advanced functionalities. Moreover, development of biomaterials is no longer separated from the other branches of biomedical engineering, particularly tissue biomechanics, musculoskeletal dynamics, and image processing aspects of skeletal radiology. In this editorial, I will discuss all the above-mentioned topics, as they constitute some of the most important trends of research on metallic biomaterials. This editorial will, therefore, serve as a foreword to the papers appearing in a special issue covering the current trends in metallic biomaterials. Full article

Research

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Open AccessArticle
Green Tea Polyphenols Coupled with a Bioactive Titanium Alloy Surface: In Vitro Characterization of Osteoinductive Behavior through a KUSA A1 Cell Study
Int. J. Mol. Sci. 2018, 19(8), 2255; https://doi.org/10.3390/ijms19082255 - 01 Aug 2018
Cited by 5
Abstract
A chemically-treated titanium alloy (Ti6Al4V) surface, able to induce hydroxyapatite precipitation from body fluids (inorganic mineralization activity), was functionalized with a polyphenolic extract from green tea (tea polyphenols, TPH). Considering that green tea polyphenols have stimulating effects on bone forming cells (biological mineralization), [...] Read more.
A chemically-treated titanium alloy (Ti6Al4V) surface, able to induce hydroxyapatite precipitation from body fluids (inorganic mineralization activity), was functionalized with a polyphenolic extract from green tea (tea polyphenols, TPH). Considering that green tea polyphenols have stimulating effects on bone forming cells (biological mineralization), the aim was to test their osteoinductive behavior due to co-operation of inorganic and biological mineralization on mesenchymal stem cells KUSA A1. The functionalized surfaces were characterized by using the Folin–Ciocalteu method and X-ray photoelectron spectroscopy to confirm the successful outcome of the functionalization process. Two cell cultures of mesenchymal stem cells, KUSA A1 were performed, with or without osteoinductive factors. The cells and surfaces were characterized for monitoring cell viability and hydroxyapatite production: Fourier Transform Infrared Spectroscopy and Raman spectroscopy analyses showed deposition of hydroxyapatite and collagen due to the cell activity, highlighting differentiation of KUSA A1 into osteoblasts. A higher production of extracellular matrix was highlighted on the functionalized samples by laser microscope and the fluorescence images showed higher viability of cells and greater presence of osteocalcin in these samples. These results highlight the ability of polyphenols to improve cell differentiation and to stimulate biological mineralization, showing that surface functionalization of metal implants could be a promising way to improve osteointegrability. Full article
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Open AccessArticle
The Influence of Selective Laser Melting (SLM) Process Parameters on In-Vitro Cell Response
Int. J. Mol. Sci. 2018, 19(6), 1619; https://doi.org/10.3390/ijms19061619 - 30 May 2018
Cited by 11
Abstract
The use of laser 3D printers is very perspective in the fabrication of solid and porous implants made of various polymers, metals, and its alloys. The Selective Laser Melting (SLM) process, in which consolidated powders are fully melted on each layer, gives the [...] Read more.
The use of laser 3D printers is very perspective in the fabrication of solid and porous implants made of various polymers, metals, and its alloys. The Selective Laser Melting (SLM) process, in which consolidated powders are fully melted on each layer, gives the possibility of fabrication personalized implants based on the Computer Aid Design (CAD) model. During SLM fabrication on a 3D printer, depending on the system applied, there is a possibility for setting the amount of energy density (J/mm3) transferred to the consolidated powders, thus controlling its porosity, contact angle and roughness. In this study, we have controlled energy density in a range 8–45 J/mm3 delivered to titanium powder by setting various levels of laser power (25–45 W), exposure time (20–80 µs) and distance between exposure points (20–60 µm). The growing energy density within studied range increased from 63 to 90% and decreased from 31 to 13 µm samples density and Ra parameter, respectively. The surface energy 55–466 mN/m was achieved with contact angles in range 72–128° and 53–105° for water and formamide, respectively. The human mesenchymal stem cells (hMSCs) adhesion after 4 h decreased with increasing energy density delivered during processing within each parameter group. The differences in cells proliferation were clearly seen after a 7-day incubation. We have observed that proliferation was decreasing with increasing density of energy delivered to the samples. This phenomenon was explained by chemical composition of oxide layers affecting surface energy and internal stresses. We have noticed that TiO2, which is the main oxide of raw titanium powder, disintegrated during selective laser melting process and oxygen was transferred into metallic titanium. The typical for 3D printed parts post-processing methods such as chemical polishing in hydrofluoric (HF) or hydrofluoric/nitric (HF/HNO3) acid solutions and thermal treatments were used to restore surface chemistry of raw powders and improve surface. Full article
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Open AccessArticle
Mechanical Characteristics, In Vitro Degradation, Cytotoxicity, and Antibacterial Evaluation of Zn-4.0Ag Alloy as a Biodegradable Material
Int. J. Mol. Sci. 2018, 19(3), 755; https://doi.org/10.3390/ijms19030755 - 07 Mar 2018
Cited by 14
Abstract
Zn-based biodegradable metallic materials have been regarded as new potential biomaterials for use as biodegradable implants, mainly because of the ideal degradation rate compared with those of Mg-based alloys and Fe-based alloys. In this study, we developed and investigated a novel Zn-4 wt [...] Read more.
Zn-based biodegradable metallic materials have been regarded as new potential biomaterials for use as biodegradable implants, mainly because of the ideal degradation rate compared with those of Mg-based alloys and Fe-based alloys. In this study, we developed and investigated a novel Zn-4 wt % Ag alloy as a potential biodegradable metal. A thermomechanical treatment was applied to refine the microstructure and, consequently, to improve the mechanical properties, compared to pure Zn. The yield strength (YS), ultimate tensile strength (UTS) and elongation of the Zn-4Ag alloy are 157 MPa, 261 MPa, and 37%, respectively. The corrosion rate of Zn-4Ag calculated from released Zn ions in DMEM extracts is approximately 0.75 ± 0.16 μg cm–2 day–1, which is higher than that of pure Zn. In vitro cytotoxicity tests showed that the Zn-4Ag alloy exhibits acceptable toxicity to L929 and Saos-2 cells, and could effectively inhibit initial bacteria adhesion. This study shows that the Zn-4Ag exhibits excellent mechanical properties, predictable degradation behavior, acceptable biocompatibility, and effective antibacterial properties, which make it a candidate biodegradable material. Full article
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Open AccessArticle
Nano-Pore Size of Alumina Affects Osteoblastic Response
Int. J. Mol. Sci. 2018, 19(2), 528; https://doi.org/10.3390/ijms19020528 - 09 Feb 2018
Cited by 7
Abstract
The rapid development and application of nanotechnology to biological interfaces has impacted the bone implant field, allowing researchers to finely modulate the interface between biomaterials and recipient tissues. In the present study, oxidative anodization was exploited to generate two alumina surfaces with different [...] Read more.
The rapid development and application of nanotechnology to biological interfaces has impacted the bone implant field, allowing researchers to finely modulate the interface between biomaterials and recipient tissues. In the present study, oxidative anodization was exploited to generate two alumina surfaces with different pore diameters. The former displayed surface pores in the mean range of 16–30 nm, while in the latter pores varied from to 65 to 89 nm. The samples were characterized by Field Emission Scanning Electron Microscopy (FESEM) and Energy Dispersive X-ray spectroscopy (EDX) analysis prior to being tested with pre-osteoblastic MC3T3-E1 cells. In vitro cell response was studied in terms of early cell adhesion, viability, and morphology, including focal adhesion quantification. Both the alumina samples promoted higher cell adhesion and viability than the control condition represented by the standard culture dish plastic. Osteogenic differentiation was assessed through alkaline phosphatase activity and extracellular calcium deposition, and it was found that of the two nano-surfaces, one was more efficient than the other. By comparing for the first time two nano-porous alumina surfaces with different pore diameters, our data supported the role of nano-topography in inducing cell response. Modulating a simple aspect of surface texture may become an attractive route for guiding bone healing and regeneration around implantable metals. Full article
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Open AccessArticle
Spot-Bonding and Full-Bonding Techniques for Fiber Reinforced Composite (FRC) and Metallic Retainers
Int. J. Mol. Sci. 2017, 18(10), 2096; https://doi.org/10.3390/ijms18102096 - 04 Oct 2017
Cited by 2
Abstract
Fiber reinforced Composite (FRC) retainers have been introduced as an aesthetic alternative to conventional metallic splints, but present high rigidity. The purpose of the present investigation was to evaluate bending and fracture loads of FRC splints bonded with conventional full-coverage of the FRC [...] Read more.
Fiber reinforced Composite (FRC) retainers have been introduced as an aesthetic alternative to conventional metallic splints, but present high rigidity. The purpose of the present investigation was to evaluate bending and fracture loads of FRC splints bonded with conventional full-coverage of the FRC with a composite compared with an experimental bonding technique with a partial (spot-) resin composite cover. Stainless steel rectangular flat, stainless steel round, and FRC retainers were tested at 0.2 and 0.3 mm deflections and at a maximum load. Both at 0.2 and 0.3 mm deflections, the lowest load required to bend the retainer was recorded for spot-bonded stainless steel flat and round wires and for spot-bonded FRCs, and no significant differences were identified among them. Higher force levels were reported for full-bonded metallic flat and round splints and the highest loads were recorded for full-bonded FRCs. At the maximum load, no significant differences were reported among spot- and full-bonded metallic splints and spot-bonded FRCs. The highest loads were reported for full bonded FRCs. The significant decrease in the rigidity of spot-bonded FRC splints if compared with full-bonded retainers suggests further tests in order to propose this technique for clinical use, as they allow physiologic tooth movement, thus presumably reducing the risk of ankylosis. Full article
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Open AccessArticle
Biocompatibility of Four Common Orthopedic Biomaterials Following a High-Salt Diet: An In Vivo Study
Int. J. Mol. Sci. 2017, 18(7), 1489; https://doi.org/10.3390/ijms18071489 - 11 Jul 2017
Cited by 3
Abstract
Nowadays, salt consumption appears to be drastically above the recommended level in industrialized countries. The health consequences of this overconsumption are heavy since high-salt intake induces cardiovascular disease, kidney dysfunction, and stroke. Moreover, harmful interaction may also occur with orthopaedic devices because overconsumption [...] Read more.
Nowadays, salt consumption appears to be drastically above the recommended level in industrialized countries. The health consequences of this overconsumption are heavy since high-salt intake induces cardiovascular disease, kidney dysfunction, and stroke. Moreover, harmful interaction may also occur with orthopaedic devices because overconsumption of salt reinforces the corrosive aspect of biological tissues and favors bone resorption process. In the present study, we aimed to assess the in vivo effect of three weeks of a high-salt diet, associated (or not) with two weeks of the neuro-myoelectrostimulation (NMES) rehabilitation program on the biocompatibility of four biomaterials used in the manufacture of arthroplasty implants. Thus, two non-metallic (PEEK and Al2O3) and two metallic (Ti6Al4V and CrCo) compounds were implanted in the rat tibial crest, and the implant-to-bone adhesion and cell viability of two surrounded muscles, the Flexor Digitorum (FD) and Tibialis Anterior (TA), were assessed at the end of the experiment. Results indicated lower adhesion strength for the PEEK implant compared to other biomaterials. An effect of NMES and a high-salt diet was only identified for Al2O3 and Ti6Al4V implants, respectively. Moreover, compared to a normal diet, a high-salt diet induced a higher number of dead cells on both muscles for all biomaterials, which was further increased for PEEK, Al2O3, and CrCo materials with NMES application. Finally, except for Ti6Al4V, NMES induced a higher number of dead cells in the directly stimulated muscle (FD) compared to the indirectly stimulated one (TA). This in vivo experiment highlights the potential harmful effect of a high-salt diet for people who have undergone arthroplasty, and a rehabilitation program based on NMES. Full article
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Review

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Open AccessReview
Applications of Metals for Bone Regeneration
Int. J. Mol. Sci. 2018, 19(3), 826; https://doi.org/10.3390/ijms19030826 - 12 Mar 2018
Cited by 18
Abstract
The regeneration of bone tissue is the main purpose of most therapies in dental medicine. For bone regeneration, calcium phosphate (CaP)-based substitute materials based on natural (allo- and xenografts) and synthetic origins (alloplastic materials) are applied for guiding the regeneration processes. The optimal [...] Read more.
The regeneration of bone tissue is the main purpose of most therapies in dental medicine. For bone regeneration, calcium phosphate (CaP)-based substitute materials based on natural (allo- and xenografts) and synthetic origins (alloplastic materials) are applied for guiding the regeneration processes. The optimal bone substitute has to act as a substrate for bone ingrowth into a defect, as well as resorb in the time frame needed for complete regeneration up to the condition of restitution ad integrum. In this context, the modes of action of CaP-based substitute materials have been frequently investigated, where it has been shown that such materials strongly influence regenerative processes such as osteoblast growth or differentiation and also osteoclastic resorption due to different physicochemical properties of the materials. However, the material characteristics needed for the required ratio between new bone tissue formation and material degradation has not been found, until now. The addition of different substances such as collagen or growth factors and also of different cell types has already been tested but did not allow for sufficient or prompt application. Moreover, metals or metal ions are used differently as a basis or as supplement for different materials in the field of bone regeneration. Moreover, it has already been shown that different metal ions are integral components of bone tissue, playing functional roles in the physiological cellular environment as well as in the course of bone healing. The present review focuses on frequently used metals as integral parts of materials designed for bone regeneration, with the aim to provide an overview of currently existing knowledge about the effects of metals in the field of bone regeneration. Full article
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Open AccessReview
The Role of Oral Cavity Biofilm on Metallic Biomaterial Surface Destruction–Corrosion and Friction Aspects
Int. J. Mol. Sci. 2018, 19(3), 743; https://doi.org/10.3390/ijms19030743 - 06 Mar 2018
Cited by 10
Abstract
Metallic biomaterials in the oral cavity are exposed to many factors such as saliva, bacterial microflora, food, temperature fluctuations, and mechanical forces. Extreme conditions present in the oral cavity affect biomaterial exploitation and significantly reduce its biofunctionality, limiting the time of exploitation stability. [...] Read more.
Metallic biomaterials in the oral cavity are exposed to many factors such as saliva, bacterial microflora, food, temperature fluctuations, and mechanical forces. Extreme conditions present in the oral cavity affect biomaterial exploitation and significantly reduce its biofunctionality, limiting the time of exploitation stability. We mainly refer to friction, corrosion, and biocorrosion processes. Saliva plays an important role and is responsible for lubrication and biofilm formation as a transporter of nutrients for microorganisms. The presence of metallic elements in the oral cavity may lead to the formation of electro-galvanic cells and, as a result, may induce corrosion. Transitional microorganisms such as sulfate-reducing bacteria may also be present among the metabolic microflora in the oral cavity, which can induce biological corrosion. Microorganisms that form a biofilm locally change the conditions on the surface of biomaterials and contribute to the intensification of the biocorrosion processes. These processes may enhance allergy to metals, inflammation, or cancer development. On the other hand, the presence of saliva and biofilm may significantly reduce friction and wear on enamel as well as on biomaterials. This work summarizes data on the influence of saliva and oral biofilms on the destruction of metallic biomaterials. Full article
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Open AccessReview
Bio-Functional Design, Application and Trends in Metallic Biomaterials
Int. J. Mol. Sci. 2018, 19(1), 24; https://doi.org/10.3390/ijms19010024 - 22 Dec 2017
Cited by 7
Abstract
Introduction of metals as biomaterials has been known for a long time. In the early development, sufficient strength and suitable mechanical properties were the main considerations for metal implants. With the development of new generations of biomaterials, the concepts of bioactive and biodegradable [...] Read more.
Introduction of metals as biomaterials has been known for a long time. In the early development, sufficient strength and suitable mechanical properties were the main considerations for metal implants. With the development of new generations of biomaterials, the concepts of bioactive and biodegradable materials were proposed. Biological function design is very import for metal implants in biomedical applications. Three crucial design criteria are summarized for developing metal implants: (1) mechanical properties that mimic the host tissues; (2) sufficient bioactivities to form bio-bonding between implants and surrounding tissues; and (3) a degradation rate that matches tissue regeneration and biodegradability. This article reviews the development of metal implants and their applications in biomedical engineering. Development trends and future perspectives of metallic biomaterials are also discussed. Full article
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Open AccessReview
Design for Additive Bio-Manufacturing: From Patient-Specific Medical Devices to Rationally Designed Meta-Biomaterials
Int. J. Mol. Sci. 2017, 18(8), 1607; https://doi.org/10.3390/ijms18081607 - 25 Jul 2017
Cited by 18
Abstract
Recent advances in additive manufacturing (AM) techniques in terms of accuracy, reliability, the range of processable materials, and commercial availability have made them promising candidates for production of functional parts including those used in the biomedical industry. The complexity-for-free feature offered by AM [...] Read more.
Recent advances in additive manufacturing (AM) techniques in terms of accuracy, reliability, the range of processable materials, and commercial availability have made them promising candidates for production of functional parts including those used in the biomedical industry. The complexity-for-free feature offered by AM means that very complex designs become feasible to manufacture, while batch-size-indifference enables fabrication of fully patient-specific medical devices. Design for AM (DfAM) approaches aim to fully utilize those features for development of medical devices with substantially enhanced performance and biomaterials with unprecedented combinations of favorable properties that originate from complex geometrical designs at the micro-scale. This paper reviews the most important approaches in DfAM particularly those applicable to additive bio-manufacturing including image-based design pipelines, parametric and non-parametric designs, metamaterials, rational and computationally enabled design, topology optimization, and bio-inspired design. Areas with limited research have been identified and suggestions have been made for future research. The paper concludes with a brief discussion on the practical aspects of DfAM and the potential of combining AM with subtractive and formative manufacturing processes in so-called hybrid manufacturing processes. Full article
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