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Labay, C., Hamouda, I., Tampieri, F., Ginebra, M. P., Canal, C., (2019). Production of reactive species in alginate hydrogels for cold atmospheric plasma-based therapies Scientific Reports 9, (1), 16160

In the last years, great advances have been made in therapies based in cold atmospheric plasmas (CAP). CAP generate reactive oxygen and nitrogen species (RONS) which can be transferred to liquids. These CAP activated liquids display the same biological efficacy (i.e. on killing cancer cells) as CAP themselves, opening the door for minimally invasive therapies. However, injection of a liquid in the body results in fast diffusion due to extracellular fluids and blood flow. Therefore, the development of efficient vehicles which allow local confinement and delivery of RONS to the diseased site is a fundamental requirement. In this work, we investigate the generation of RONS (H2O2, NO2−, short-lived RONS) in alginate hydrogels by comparing two atmospheric pressure plasma jets: kINPen and a helium needle, at a range of plasma treatment conditions (time, gas flow, distance to the sample). The physic-chemical properties of the hydrogels remain unchanged by the plasma treatment, while the hydrogel shows several-fold larger capacity for generation of RONS than a typical isotonic saline solution. Part of the RONS are quickly released to a receptor media, so special attention has to be put on the design of hydrogels with in-situ crosslinking. Remarkably, the hydrogels show capacity for sustained release of the RONS. The plasma-treated hydrogels remain fully biocompatible (due the fact that the species generated by plasma are previously washed away), indicating that no cytotoxic modifications have occurred on the polymer. Moreover, the RONS generated in alginate solutions showed cytotoxic potential towards bone cancer cells. These results open the door for the use of hydrogel-based biomaterials in CAP-associated therapies.

Keywords: Biomedical materials, Plasma physics

Aparicio, C., Salvagni, E., Werner, M., Engel, E., Pegueroles, M., Rodriguez-Cabello, C., Munoz, F., Planell, J. A., Gil, J., (2009). Biomimetic treatments on dental implants for immediate loading applications Journal of Medical Devices , 3, (2), 027555

Summary form only given. Commercially pure titanium (cp Ti) dental implants have been widely and successfully used with high rates of clinical success in normal situations. However, there is still a lack of reliable synthetic materials to be used either a) when immediate loading of the implant is desired or b) when bone presents compromised conditions due to trauma, infection, systemic disease and/or lack of significant bone volume. Our group has aimed the development of biomimetic strategies of surface modification to obtain metallic implants with osteostimulative capabilities. These surface modifications will provide implants with a rapid rate of newly-formed bone growth and with ossecoalescence, i.e., direct chemical contact with the surrounding tissues. Consequently, the biomimetically-modified implants will be reliably used on those more demanding clinical situations, cp Ti surfaces treated to obtain a combination of an optimal random surface topography (in the micro and nanolevels) with a chemical modification of the naturally-formed titania layer have been proved bioactive. These rough and bioactive surfaces nucleate and grow a homogeneous hydroxyapatite layer both in vitro and in vivo. They stimulate the osteoblasts differentiation and trigger a rapid bone formation that mechanically fixes implants under immediate-loading conditions. A simple process using silane chemistry has been proved specific, rapid, and reliable to covalently immobilize biomolecules on cp Ti surfaces. This methodology can be used to develop biofunc- tionalized implant surfaces with different or combined bioactivities. The biofunctional molecules can be biopolymers, proteins, growth factors, and synthetic peptides specifically designed to be attached to the surface. The bioactive properties of the molecules designed and used can be mineral growing and nucleation, osteoblast differentiation (bone regeneration), fibroblasts differentiation (biological sealing), antibiotic,... Specifically, we have obtained mechanically and thermochemically stable coatings made of recombinant elastin-like biopolymers. The biopolymers bear either a) the RODS peptide, which is a highly-specific cell-adhesion motif present in proteins of the extracellular matrix for different tissues including bone, or b) an acidic peptide sequence derived from statherin, a protein present in saliva with high affinity for calcium-phosphates and with a leading role in the remineralization processes of the hard tissues forming our teeth. Two different biomimetic strategies have been successfully developed combining topographical modification, inorganic treatments and/or biofunctionalization for improving bioactive integrative properties of cp Ti implants.

Keywords: Biomedical materials, Bone, Cellular biophysics, Dentistry, Molecular biophysics, Prosthetics, Proteins, Surface treatment, Titanium

Koch, M. A., Engel, E., Planell, J. A., Lacroix, D., (2008). Cell seeding and characterisation of PLA/glass composite scaffolds for bone tissue engineering Journal of Biomechanics 16th Congress, European Society of Biomechanics , Elsevier (Lucerne, Switzerland) 41, (Supplement 1), S162

In this study polymer-glass composite scaffolds were characterized by permeability and porosity, two important properties for the use in perfusion bioreactors. These scaffolds were seeded with osteoblast-like cells to assess the efficiency of the used bioreactor. The used PLA/glass composite scaffolds are adequate for the perfusion culture. The high porosity and pore interconnectivity allow an even cell distribution and incorporation of a high cell number. For optimisation of the perfusion bioreactor system, further research has to be dedicated to the cell seeding and culture.

Keywords: Biomedical materials, Bioreactors, Bone, Cellular biophysics, Composite materials, Orthopaedics, Permeability, Polymers, Porosity, Porous materials, Tissue engineering

Rodriguez, Segui, Bucior, I., Burger, M. M., Samitier, J., Errachid, A., Fernàndez-Busquets, X., (2007). Application of a bio-QCM to study carbohydrates self-interaction in presence of calcium Transducers '07 & Eurosensors Xxi, Digest of Technical Papers 14th International Conference on Solid-State Sensors, Actuators and Microsystems , IEEE (Lyon, France) 1-2, 1995-1998

In the past years, the quartz crystal microbalance (QCM) has been successfully applied to follow interfacial physical chemistry phenomena in a label free and real time manner. However, carbohydrate self adhesion has only been addressed partially using this technique. Carbohydrates play an important role in cell adhesion, providing a highly versatile form of attachment, suitable for biologically relevant recognition events in the initial steps of adhesion. Here, we provide a QCM study of carbohydrates' self-recognition in the presence of calcium, based on a species-specific cell recognition model provided by marine sponges. Our results show a difference in adhesion kinetics when varying either the calcium concentration (with a constant carbohydrate concentration) or the carbohydrate concentration (with constant calcium concentration).

Keywords: Biomedical materials, Calcium, Cellular biophysics, Microbalances, Porous materials, Quartz, Surface chemistry/ bio-QCM, Carbohydrates self-interaction, Quartz crystal microbalance, Interfacial physical chemistry phenomena, Carbohydrate self adhesion, Biologically relevant recognition events, Marine sponges, Adhesion kinetics, Calcium concentration, Carbohydrate concentration, Biosensors, Biomedical materials, Surface chemistry, Cellular biophysics