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by Keyword: Gallium

Pinera-Avellaneda, David, Buxadera-Palomero, Judit, Delint, Rosalia Cuahtecontzi, Dalby, Matthew J, Burgess, Karl V, Ginebra, Maria-Pau, Ruperez, Elisa, Manero, Jose Maria, (2024). Gallium and silver-doped titanium surfaces provide enhanced osteogenesis, reduce bone resorption and prevent bacterial infection in co-culture Acta Biomaterialia 180, 154-170

Bacterial infection remains a significant problem associated with orthopaedic surgeries leading to surgical site infection (SSI). This unmet medical need can become an even greater complication when surgery is due to malignant bone tumor. In the present study, we evaluated in vitro titanium (Ti) implants subjected to gallium (Ga) and silver (Ag)-doped thermochemical treatment as strategy to prevent SSI and improve osteointegration in bone defects caused by diseases such as osteoporosis, bone tumor, or bone metastasis. Firstly, as Ga has been reported to be an osteoinductive and anti-resorptive agent, its performance in the mixture was proved by studying human mesenchymal stem cells (hMSC) and pre-osteoclasts (RAW264.7) behaviour. Then, the antibacterial potential provided by Ag was assessed by resembling "The Race for the Surface" between hMSC and Pseudomonas aeruginosa in two co-culture methods. Moreover, the presence of quorum sensing molecules in the co-culture was evaluated. The results highlighted the suitability of the mixture to induce osteodifferentiation and reduce osteoclastogenesis in vitro . Furthermore, the GaAg surface promoted strong survival rate and retained osteoinduction potential of hMSCs even after bacterial inoculation. Therefore, GaAg-modified titanium may be an ideal candidate to repair bone defects caused by excessive bone resorption, in addition to preventing SSI.

JTD Keywords: Antibacteria, Antibacterial, Bone resorption, Expression, Gallium, In-vitro, Ligan, Nf-kappa-b, Nfatc1, Osteoclast formation, Phosphatase, Receptor activator, Silver, Ti metal, Titanium


Piñera-Avellaneda, D, Buxadera-Palomero, J, Ginebra, MP, Rupérez, E, Manero, JM, (2023). Gallium-doped thermochemically treated titanium reduces osteoclastogenesis and improves osteodifferentiation Frontiers In Bioengineering And Biotechnology 11, 1303313

Excessive bone resorption is one of the main causes of bone homeostasis alterations, resulting in an imbalance in the natural remodeling cycle. This imbalance can cause diseases such as osteoporosis, or it can be exacerbated in bone cancer processes. In such cases, there is an increased risk of fractures requiring a prosthesis. In the present study, a titanium implant subjected to gallium (Ga)-doped thermochemical treatment was evaluated as a strategy to reduce bone resorption and improve osteodifferentiation. The suitability of the material to reduce bone resorption was proven by inducing macrophages (RAW 264.7) to differentiate to osteoclasts on Ga-containing surfaces. In addition, the behavior of human mesenchymal stem cells (hMSCs) was studied in terms of cell adhesion, morphology, proliferation, and differentiation. The results proved that the Ga-containing calcium titanate layer is capable of inhibiting osteoclastogenesis, hypothetically by inducing ferroptosis. Furthermore, Ga-containing surfaces promote the differentiation of hMSCs into osteoblasts. Therefore, Ga-containing calcium titanate may be a promising strategy for patients with fractures resulting from an excessive bone resorption disease.Copyright © 2023 Piñera-Avellaneda, Buxadera-Palomero, Ginebra, Rupérez and Manero.

JTD Keywords: biology, bone metastasis, differentiation, ferroptosis, gallium, iron, mouse, osteoclast, osteoporosis, Bone metastasis, Ferroptosis, Gallium, Osteoclast, Osteoporosis, Ti metal, Titanium implant


Rodríguez-Contreras, A, Torres, D, Piñera-Avellaneda, D, Pérez-Palou, L, Ortiz-Hernández, M, Ginebra, MP, Calero, JA, Manero, JM, Rupérez, E, (2023). Dual-Action Effect of Gallium and Silver Providing Osseointegration and Antibacterial Properties to Calcium Titanate Coatings on Porous Titanium Implants International Journal Of Molecular Sciences 24, 8762

Previously, functional coatings on 3D-printed titanium implants were developed to improve their biointegration by separately incorporating Ga and Ag on the biomaterial surface. Now, a thermochemical treatment modification is proposed to study the effect of their simultaneous incorporation. Different concentrations of AgNO3 and Ga(NO3)3 are evaluated, and the obtained surfaces are completely characterized. Ion release, cytotoxicity, and bioactivity studies complement the characterization. The provided antibacterial effect of the surfaces is analyzed, and cell response is assessed by the study of SaOS-2 cell adhesion, proliferation, and differentiation. The Ti surface doping is confirmed by the formation of Ga-containing Ca titanates and nanoparticles of metallic Ag within the titanate coating. The surfaces generated with all combinations of AgNO3 and Ga(NO3)3 concentrations show bioactivity. The bacterial assay confirms a strong bactericidal impact achieved by the effect of both Ga and Ag present on the surface, especially for Pseudomonas aeruginosa, one of the main pathogens involved in orthopedic implant failures. SaOS-2 cells adhere and proliferate on the Ga/Ag-doped Ti surfaces, and the presence of gallium favors cell differentiation. The dual effect of both metallic agents doping the titanium surface provides bioactivity while protecting the biomaterial from the most frequent pathogens in implantology.

JTD Keywords: 3d-printing, agent, antibacterial activity, bioactive ti, biomaterials, coatings, competition, cu, gallium, glasses, ions, metal, porous structures, promote osseointegration, silver, titanium implants, In-vitro, Porous structures, Titanium implants


Ebrahimi, N, Bi, CH, Cappelleri, DJ, Ciuti, G, Conn, AT, Faivre, D, Habibi, N, Hosovsky, A, Iacovacci, V, Khalil, ISM, Magdanz, V, Misra, S, Pawashe, C, Rashidifar, R, Soto-Rodriguez, PED, Fekete, Z, Jafari, A, (2021). Magnetic Actuation Methods in Bio/Soft Robotics Advanced Functional Materials 31, 2005137

© 2020 Wiley-VCH GmbH In recent years, magnetism has gained an enormous amount of interest among researchers for actuating different sizes and types of bio/soft robots, which can be via an electromagnetic-coil system, or a system of moving permanent magnets. Different actuation strategies are used in robots with magnetic actuation having a number of advantages in possible realization of microscale robots such as bioinspired microrobots, tetherless microrobots, cellular microrobots, or even normal size soft robots such as electromagnetic soft robots and medical robots. This review provides a summary of recent research in magnetically actuated bio/soft robots, discussing fabrication processes and actuation methods together with relevant applications in biomedical area and discusses future prospects of this way of actuation for possible improvements in performance of different types of bio/soft robots.

JTD Keywords: capsule endoscope, controlled propulsion, conventional gastroscopy, digital microfluidics, guided capsule, liquid-metal, magnetic drug delivery, magnetic microrobots, magnetically guided capsule endoscopy, magnetotactic bacteria, nanoscribe ip-dip, navigation system, Gallium-indium egain, Magnetic bioinspired micromanipulation, Magnetic drug delivery, Magnetic microrobots, Magnetically guided capsule endoscopy, Magnetotactic bacteria


Rodríguez-Contreras, A., Torres, D., Guillem-Marti, J., Sereno, P., Ginebra, M. P., Calero, J. A., Manero, J. M., Rupérez, E., (2020). Development of novel dual-action coatings with osteoinductive and antibacterial properties for 3D-printed titanium implants Surface and Coatings Technology 403, 126381

Gallium (Ga) has been recently proposed as a novel therapeutic agent, since it promotes bone formation and exhibits antibacterial properties. This work focuses on the optimization of a thermochemical treatment that incorporates Ga ions by the addition of the body-friendly Ga nitrate approved by the Food and Drug Administration. The objective was to simultaneously provide the inner and the outer surfaces of porous‑titanium surfaces obtained by 3D-printing with bioactivity and antibacterial properties. The apatite-forming ability of the coating, as well as the antibacterial activity and SaOS-2 cell adhesion, proliferation, differentiation and mineralization were evaluated and compared with untreated Ti surfaces. The characterization of the surfaces revealed the presence of a Ga-containing calcium titanate layer, which was non cytotoxic and in simulated body fluid produced a homogeneous apatite coating well adhered to the substrate. The formation of this apatite layer was accelerated with increasing Ga amounts present on the surface, resulting also in an increase in thickness. An initial quick release of Ga ion promoted the antibacterial effect against gram positive strains, especially for Pseudomonas aeruginosa, one of the most frequent resistant pathogens in nosocomial infections. SaOS-2 cells adhered and proliferated on the Ga-doped Ti surfaces, its presence contributed to cell differentiation and to considerably increase the mineralization levels. Thus, the developed multifunctional coatings could provide bioactivity to the porous Ti implants while protecting them from the most frequent gram-negative pathogens.

JTD Keywords: 3D-printing, Antibacterial activity, Biomaterials, Gallium, Porous structures, Titanium implants