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Titanium-Based Biomaterials and Their Applications
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Titanium-Based Biomaterials and Their Applications

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 (30 June 2023) | Viewed by 12115

Special Issue Editors

Prof. Dr. Javier Gil

E-Mail Website
Guest Editor
Bioengineering Institute of Technology, School of Dentistry, Universitat Internacional de Catalunya C/ Immaculada, 22 08017 Barcelona, Spain
Interests: biomaterials; titanium and its alloys; shape memory alloys; dental materials
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Juan Manuel Aragoneses

E-Mail Website
Guest Editor
Dean of the Faculty of Dentistry, Universidad Alfonso X El Sabio, 28691 Madrid, Spain
Interests: Dentsitry; Dental materials; dental implants; prothesis; biological-material interactions

Special Issue Information

Dear Colleagues,

Modifications to titanium surfaces for biomedical applications are constantly increasibg. Biofunciuonalisation is one of the keys to improving the efficacy of implants, because it carries molecules with specific functions that improve therapeutic action and reduce treatment time. Molecular actions, signaling, mechanism, effect and in vitro and in vivo experiences are welcomed in this Special Issue.

Titanium implants with, among the most important, bactericidal, bacteriostatic, osseointegrative, anti-inflammatory and anticarcinogenic agents, mark progress in the field of biomaterials.
In this Special Issue, we want to provide an opportunity to publish research on these topics, which are of great interest for clinicians of all medical specialties, researchers in materials science, and biochemists, organic chemists, veterinarians and others.

We invite you to submit your contributions to this prestigious journal. Thank you very much for your attention and we look forward to seeing you in the Special Issue.

Prof. Dr. Javier Gil
Prof. Dr. Juan Manuel Aragoneses
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • titanium alloys
  • low modulus alloys
  • biocompatibility
  • bioactive titanium
  • biofunctionalized titanium
  • bactericide titanium
  • shape memory titanium alloys
  • properties of titanium alloys
  • porous titanium

Published Papers (6 papers)

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Research

16 pages, 2760 KiB  
Article
Comparison of the Antibacterial Effect of Silver Nanoparticles and a Multifunctional Antimicrobial Peptide on Titanium Surface
by Daniel Moreno, Judit Buxadera-Palomero, Maria-Pau Ginebra, José-María Manero, Helena Martin-Gómez, Carlos Mas-Moruno and Daniel Rodríguez
Int. J. Mol. Sci. 2023, 24(11), 9739; https://doi.org/10.3390/ijms24119739 - 04 Jun 2023
Cited by 1 | Viewed by 1479
Abstract
Titanium implantation success may be compromised by Staphylococcus aureus surface colonization and posterior infection. To avoid this issue, different strategies have been investigated to promote an antibacterial character to titanium. In this work, two antibacterial agents (silver nanoparticles and a multifunctional antimicrobial peptide) [...] Read more.
Titanium implantation success may be compromised by Staphylococcus aureus surface colonization and posterior infection. To avoid this issue, different strategies have been investigated to promote an antibacterial character to titanium. In this work, two antibacterial agents (silver nanoparticles and a multifunctional antimicrobial peptide) were used to coat titanium surfaces. The modulation of the nanoparticle (≈32.1 ± 9.4 nm) density on titanium could be optimized, and a sequential functionalization with both agents was achieved through a two-step functionalization method by means of surface silanization. The antibacterial character of the coating agents was assessed individually as well as combined. The results have shown that a reduction in bacteria after 4 h of incubation can be achieved on all the coated surfaces. After 24 h of incubation, however, the individual antimicrobial peptide coating was more effective than the silver nanoparticles or their combination against Staphylococcus aureus. All tested coatings were non-cytotoxic for eukaryotic cells. Full article
(This article belongs to the Special Issue Titanium-Based Biomaterials and Their Applications)
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14 pages, 3563 KiB  
Article
Osteoblastic Cell Behavior and Gene Expression Related to Bone Metabolism on Different Titanium Surfaces
by Eugenio Velasco-Ortega, Isabel Fos-Parra, Daniel Cabanillas-Balsera, Javier Gil, Iván Ortiz-García, Mercè Giner, Jesús Bocio-Núñez, María-José Montoya-García and Álvaro Jiménez-Guerra
Int. J. Mol. Sci. 2023, 24(4), 3523; https://doi.org/10.3390/ijms24043523 - 09 Feb 2023
Cited by 3 | Viewed by 1502
Abstract
The surface topography of titanium dental implants has a great influence on osseointegration. In this work, we try to determine the osteoblastic behavior and gene expression of cells with different titanium surfaces and relate them to the physicochemical properties of the surface. For [...] Read more.
The surface topography of titanium dental implants has a great influence on osseointegration. In this work, we try to determine the osteoblastic behavior and gene expression of cells with different titanium surfaces and relate them to the physicochemical properties of the surface. For this purpose, we have used commercial titanium discs of grade 3: as-received corresponds to machined titanium without any surface treatment (MA), chemically acid etched (AE), treated via sand blasting with Al2O3 particles (SB) and a sand-blasting treatment with acid etching (SB+AE). The surfaces have been observed using scanning electron microscopy (SEM) and the roughness, wettability and surface energy with dispersive and polar components have been characterized. Osteoblastic cultures were performed with SaOS-2 osteoblastic cells determining cell viability as well as alkaline phosphatase levels for 3 and 21 days, and osteoblastic gene expression was determined. The roughness values of the MA discs was 0.02 μm, which increases to 0.3 μm with acid attack and becomes the maximum for the sand-blasted samples, reaching values of 1.2 μm for SB and SB+AE. The hydrophilic behavior of the MA and AE samples with contact angles of 63° and 65° is superior to that of the rougher samples, being 75° for SB and 82° for SB+AE. In all cases, they show good hydrophilicity. GB and GB+AE surfaces present a higher polar component in the surface energy values, 11.96 and 13.18 mJ/m2, respectively, than AE and MA, 6.64 and 9.79 mJ/m2, respectively. The osteoblastic cell viability values at three days do not show statistically significant differences between the four surfaces. However, the viability of the SB and SB+AE surfaces at 21 days is much higher than that of the AE and MA samples. From the alkaline phosphatase studies, higher values were observed for those treated with sand blasting with and without acid etching compared to the other two surfaces, indicating a greater activity in osteoblastic differentiation. In all cases except in the Osterix (Ostx) —osteoblast-specific transcription factor—a decrease in gene expression is observed in relation to the MA samples (control). The most important increase was observed for the SB+AE condition. A decrease in the gene expression of Osteoprotegerine (OPG), Runt-related transcription factor 2 (Runx2), Receptor Activator of NF-κB Ligand (RANKL) and Alkaline Phosphatase (Alp) genes was observed in the AE surface. Full article
(This article belongs to the Special Issue Titanium-Based Biomaterials and Their Applications)
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14 pages, 2885 KiB  
Article
Peptides for Coating TiO2 Implants: An In Silico Approach
by Almerinda Agrelli, Niedja Fittipaldi Vasconcelos, Rayane Cristine Santos da Silva, Carina Lucena Mendes-Marques, Isabel Renata de Souza Arruda, Priscilla Stela Santana de Oliveira, Luzia Rejane Lisbôa Santos, Audrey Nunes de Andrade, Ronald Rodrigues de Moura, Lucas Coelho Bernardo-Menezes, Natália Pereira da Silva and Giovanna Machado
Int. J. Mol. Sci. 2022, 23(22), 14048; https://doi.org/10.3390/ijms232214048 - 14 Nov 2022
Cited by 2 | Viewed by 1260
Abstract
Titanium is usually used in the manufacturing of metal implants due to its biocompatibility and high resistance to corrosion. A structural and functional connection between the living bone and the surface of the implant, a process called osseointegration, is mandatory for avoiding prolonged [...] Read more.
Titanium is usually used in the manufacturing of metal implants due to its biocompatibility and high resistance to corrosion. A structural and functional connection between the living bone and the surface of the implant, a process called osseointegration, is mandatory for avoiding prolonged healing, infections, and tissue loss. Therefore, osseointegration is crucial for the success of the implantation procedure. Osseointegration is a process mediated by bone-matrix progenitor cells’ proteins, named integrins. In this study, we used an in silico approach to assemble and test peptides that can be strategically used in sensitizing TiO2 implants in order to improve osseointegration. To do so, we downloaded PDB structures of integrins α5β1, αvβ3, and αIIbβ3; their biological ligands; and low-cost proteins from the Protein Data Bank, and then we performed a primary (integrin-protein) docking analysis. Furthermore, we modeled complex peptides with the potential to bind to the TiO2 surface on the implant, as well as integrins in the bone-matrix progenitor cells. Then we performed a secondary (integrin–peptide) docking analysis. The ten most promising integrin–peptide docking results were further verified by molecular dynamics (MD) simulations. We recognized 82 peptides with great potential to bind the integrins, and therefore to be used in coating TiO2 implants. Among them, peptides 1 (GHTHYHAVRTQTTGR), 3 (RKLPDATGR), and 8 (GHTHYHAVRTQTLKA) showed the highest binding stability during the MD simulations. This bioinformatics approach saves time and more effectively directs in vitro studies. Full article
(This article belongs to the Special Issue Titanium-Based Biomaterials and Their Applications)
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13 pages, 2495 KiB  
Article
Effect of the Size of Titanium Particles Released from Dental Implants on Immunological Response
by Juan Antonio Callejas, Javier Gil, Aritza Brizuela, Román A. Pérez and Begoña M. Bosch
Int. J. Mol. Sci. 2022, 23(13), 7333; https://doi.org/10.3390/ijms23137333 - 30 Jun 2022
Cited by 5 | Viewed by 1895
Abstract
The techniques used in oral implantology to remove bacterial biofilm from the surface of implants by machining the titanium surface (implantoplasty) or by placing rough dental implants through friction with the cortical bone generate a large release of particles. In this work, we [...] Read more.
The techniques used in oral implantology to remove bacterial biofilm from the surface of implants by machining the titanium surface (implantoplasty) or by placing rough dental implants through friction with the cortical bone generate a large release of particles. In this work, we performed a simulation of particle generation following clinical protocols. The particles were characterized for commercially pure titanium with particle sizes of 5, 10, 15, and 30 μm. The aim was to determine the effect of particle size and chemical composition of the implant on the immune response. For this purpose, their morphology and possible contamination were characterized by scanning electron microscopy and X-ray microanalysis. In addition, the granulometry, specific surface area, release of metal ions into the medium, and studies of cytocompatibility, gene expression, and cytokine release linked to the inflammatory process were studied. The release of ions for titanium particles showed levels below 800 ppb for all sizes. Smaller particle sizes showed less cytotoxicity, although particles of 15 μm presented higher levels of cytocompatibility. In addition, inflammatory markers (TNFα and Il-1β) were higher compared to larger titanium. Specifically, particles of 15 μm presented a lower proinflammatory and higher anti-inflammatory response as characterized by gene expression and cytokine release, compared to control or smaller particles. Therefore, in general, there is a greater tendency for smaller particles to produce greater toxicity and a greater proinflammatory response. Full article
(This article belongs to the Special Issue Titanium-Based Biomaterials and Their Applications)
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15 pages, 12104 KiB  
Article
Titanium Surface Characteristics Induce the Specific Reprogramming of Toll-like Receptor Signaling in Macrophages
by Zaira González-Sánchez, Victoria Areal-Quecuty, Alvaro Jimenez-Guerra, Daniel Cabanillas-Balsera, Francisco Javier Gil, Eugenio Velasco-Ortega and David Pozo
Int. J. Mol. Sci. 2022, 23(8), 4285; https://doi.org/10.3390/ijms23084285 - 13 Apr 2022
Cited by 2 | Viewed by 2033
Abstract
Most of the research on titanium-based dental implants (Ti-discs) is focused on how they are able to stimulate the formation of new tissue and/or cytotoxic studies, with very scarce data on their effects on functional responses by immunocompetent cells. In particular, the link [...] Read more.
Most of the research on titanium-based dental implants (Ti-discs) is focused on how they are able to stimulate the formation of new tissue and/or cytotoxic studies, with very scarce data on their effects on functional responses by immunocompetent cells. In particular, the link between the rewiring of innate immune responses and surface biomaterials properties is poorly understood. To address this, we characterize the functional response of macrophage cultures to four different dental titanium surfaces (MA: mechanical abrasion; SB + AE: sandblasting plus etching; SB: sandblasting; AE: acid etching). We use different Toll-like receptor (TLR) ligands towards cell surface receptors (bacterial lipopolysaccharide LPS for TLR4; imiquimod for TLR7; synthetic bacterial triacylated lipoprotein for TLR2/TLR1) and endosomal membrane receptor (poly I:C for TLR3) to simulate bacterial (cell wall bacterial components) or viral infections (dsRNA and ssRNA). The extracellular and total LDH levels indicate that exposure to the different Ti-surfaces is not cytotoxic for macrophages under resting or TLR-stimulated conditions, although there is a tendency towards an impairment in macrophage proliferation, viability or adhesion under TLR4, TLR3 and TLR2/1 stimulations in SB discs cultures. The secreted IL-6 and IL-10 levels are not modified upon resting macrophage exposure to the Ti-surfaces studied as well as steady state levels of iNos or ArgI mRNA. However, macrophage exposure to MA Ti-surface do display an enhanced immune response to TLR4, TLR7 or TLR2/1 compared to other Ti-surfaces in terms of soluble immune mediators secreted and M1/M2 gene expression profiling. This change of characteristics in cellular phenotype might be related to changes in cellular morphology. Remarkably, the gene expression of Tlr3 is the only TLR that is differentially affected by distinct Ti-surface exposure. These results highlight the relevance of patterned substrates in dental implants to achieve a smart manipulation of the immune responses in the context of personalized medicine, cell-based therapies, preferential lineage commitment of precursor cells or control of tissue architecture in oral biology. Full article
(This article belongs to the Special Issue Titanium-Based Biomaterials and Their Applications)
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26 pages, 50519 KiB  
Article
On-Growth and In-Growth Osseointegration Enhancement in PM Porous Ti-Scaffolds by Two Different Bioactivation Strategies: Alkali Thermochemical Treatment and RGD Peptide Coating
by Katrin Steffanie Rappe, Monica Ortiz-Hernandez, Miquel Punset, Meritxell Molmeneu, Albert Barba, Carles Mas-Moruno, Jordi Guillem-Marti, Cristina Caparrós, Elisa Rupérez, José Calero, María-Cristina Manzanares, Javier Gil and Jordi Franch
Int. J. Mol. Sci. 2022, 23(3), 1750; https://doi.org/10.3390/ijms23031750 - 03 Feb 2022
Cited by 10 | Viewed by 2728
Abstract
A lack of primary stability and osteointegration in metallic implants may result in implant loosening and failure. Adding porosity to metallic implants reduces the stress shielding effect and improves implant performance, allowing the surrounding bone tissue to grow into the scaffold. However, a [...] Read more.
A lack of primary stability and osteointegration in metallic implants may result in implant loosening and failure. Adding porosity to metallic implants reduces the stress shielding effect and improves implant performance, allowing the surrounding bone tissue to grow into the scaffold. However, a bioactive surface is needed to stimulate implant osteointegration and improve mechanical stability. In this study, porous titanium implants were produced via powder sintering to create different porous diameters and open interconnectivity. Two strategies were used to generate a bioactive surface on the metallic foams: (1) an inorganic alkali thermochemical treatment, (2) grafting a cell adhesive tripeptide (RGD). RGD peptides exhibit an affinity for integrins expressed by osteoblasts, and have been reported to improve osteoblast adhesion, whereas the thermochemical treatment is known to improve titanium implant osseointegration upon implantation. Bioactivated scaffolds and control samples were implanted into the tibiae of rabbits to analyze the effect of these two strategies in vivo regarding bone tissue regeneration through interconnected porosity. Histomorphometric evaluation was performed at 4 and 12 weeks after implantation. Bone-to-implant contact (BIC) and bone in-growth and on-growth were evaluated in different regions of interest (ROIs) inside and outside the implant. The results of this study show that after a long-term postoperative period, the RGD-coated samples presented higher quantification values of quantified newly formed bone tissue in the implant’s outer area. However, the total analyzed bone in-growth was observed to be slightly greater in the scaffolds treated with alkali thermochemical treatment. These results suggest that both strategies contribute to enhancing porous metallic implant stability and osteointegration, and a combination of both strategies might be worth pursuing. Full article
(This article belongs to the Special Issue Titanium-Based Biomaterials and Their Applications)
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