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Biomedical subjects

Rui L Reis

Publications and source records attributed to Rui L Reis.

At least 19 recordsLinked to original sources
PubMed2004

Cytokine secretion from mononuclear cells cultured in vitro with starch-based polymers and poly-L-lactide.

The cytokine network is one of the major controlling systems of the inflammatory process, driving the magnitude and duration of the host response against invading microorganisms, foreign materials, or altered internal stimuli. Pro- and antiinflammatory cytokines were quantified after in vitro culture of a mixed population of monocytes/macrophages and lymphocytes with biodegradable polymers. Different blends of starch-based polymers and their composites filled with hydroxyapatite were studied and compared with poly-L-lactide. Interleukin (IL)-1beta, IL-6, and tumour necrosis factor-alpha were investigated as the markers of immunological reactivity because they are known to act at the early stages of injury/invasion. Interferon-gamma, recognized as a proinflammatory cytokine, although not present during early responses was also investigated. Contrarily, IL-4 derived from T lymphocytes, was investigated because it is an immunoregulator that counteracts some aspects of inflammation. T lymphocyte activation was also determined by quantifying IL-2. The results support the hypothesis that different biodegradable polymers can affect mononuclear cell activation and the production of several cytokines associated with the inflammatory process. No IL-2 or interferon-gamma was found in the culture supernatants after 3, 7, and 14 days in the presence of any of the materials. IL-6 was detected in the highest amounts, for all the conditions, followed by tumour necrosis factor-alpha. IL-1beta was produced in very low amounts, being undetectable with some of the starch-based materials. IL-4 was the only cytokine that did not demonstrate any significant difference within this group of materials. Starch-based polymers and composites induced lower production of proinflammatory cytokines in comparison to poly-L-lactide.

Cells, Cultured↗
PubMed2004

The behavior of novel hydrophilic composite bone cements in simulated body fluids.

Composite bone cements were formulated with bioactive glass (MgO--SiO(2)--3CaO. P(2)O(5)) as the filler and hydrophilic matrix. The matrix was composed of a starch/cellulose acetate blend (SCA) as the solid component and a mixture of methylmethacrylate/acrylic acid (MMA/AA) as the liquid component. The curing parameters, mechanical properties, and bioactive behavior of these composite cements were determined. The addition of up to 30 wt % of glass improved both compressive modulus and yield strength and kept the maximum curing temperature at the same value presented by a typical acrylic-based commercial formulation. The lack of a strongly bonded interface (because no coupling agent was used) had important effects on the swelling and mechanical properties of the novel bone cements. However, bone cements containing AA did not show a bioactive behavior, because of the deleterious effect of this monomer on the calcium phosphate precipitation on the polymeric surfaces. Formulations without AA were prepared with MMA or 2-hydroxyethyl methacrylate (HEMA) as the liquid component. Only these formulations could form an apatite-like layer on their surface. These systems, therefore, are very promising: They are bioactive, hydrophilic, partially degradable, and present interesting mechanical properties. This combination of properties could facilitate the release of bioactive agents from the cement, allow bone ingrowth in the cement, and induce a press-fitting effect, improving the interfaces with both the prosthesis and the bone.

Acrylates↗
PubMed2004

Controlled delivery achieved with bi-layer matrix devices produced by co-injection moulding.

The aim of this study was to design new soy protein-based bi-layered co-injection moulded matrix systems aimed to achieve controlled drug delivery. The devices consisted of a drug-free outer layer (skin) and a drug-containing core. The systems overcame the inherent disadvantage of non-linear release associated with diffusion-controlled single-layer matrix devices by providing additional releasing area with time to compensate for the decreasing release rate. As expected, the bi-layer devices presented a significant decrease in drug release rate when compared with a correspondent single layer matrix system. The skin thickness and the degree of crosslinking of the core appeared to be very important tools to tailor the release patterns. Furthermore, due to the amphoteric nature of the soy protein, the developed devices evidenced a pH-dependent behaviour. The mechanisms of drug release were also elucidated at two different pH values: i) pH 5.0, near the isoelectric point of soy (low matrix solubility); and ii) pH 7.4, physiological pH (high matrix solubility). Consequently, changing the release medium from pH 5.0 to pH 7.4 after two hours, led to an abrupt increase in drug release and the devices presented a typical controlled drug delivery profile: slow release/fast release. These evidences may provide for the development of individual systems with different release onsets that in combination may exhibit drug releases at predetermined times in a pre-programmed way. Another possibility is the production of three-layer devices presenting bimodal release profiles (fast release/slow release/fast release) by similar technologies. Scanning electron micrograph of a developed bi-layer device.

Biocompatible Materials↗
PubMed2004

Production and characterization of chitosan fibers and 3-D fiber mesh scaffolds for tissue engineering applications.

This study reports on the production of chitosan fibers and 3-D fiber meshes for the use as tissue engineering scaffolds. Both structures were produced by means of a wet spinning technique. Maximum strain at break and tensile strength of the developed fibers were found to be 8.5% and 204.9 MPa, respectively. After 14 d of immersion in simulated body fluid (SBF), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and inductively coupled plasma emission (ICP) spectroscopy analyses showed that a bioactive Ca-P layer was formed on the surface of the fibers, meaning that they exhibit a bioactive behavior. The samples showed around 120% max. swelling in physiological conditions. The pore sizes of 3-D chitosan fiber mesh scaffolds were observed to be in the range of 100-500 microm by SEM. The equilibrium-swelling ratio of the developed scaffolds was found to be around 170% (w/w) in NaCl solution at 37 degrees C. Besides that, the limit swelling strain was less than 30%, as obtained by mechanical spectroscopy measurements in the same conditions. The viscoelastic properties of the scaffolds were also evaluated by both creep and dynamic mechanical tests. By means of using short-term MEM extraction test, both types of structures (fibers and scaffolds) were found to be non-cytotoxic to fibroblasts. Furthermore, osteoblasts directly cultured over chitosan fiber mesh scaffolds presented good morphology and no inhibition of cell proliferation could be observed.Osteoblast-like cells proliferating over chitosan based fibers after 7 d of culture.

Animals↗
PubMed2004

Fibers and 3D mesh scaffolds from biodegradable starch-based blends: production and characterization.

The aim of this work is the production of fibers from biodegradable polymers to obtain 3D scaffolds for tissue engineering of hard tissues. The scaffolds required for this highly demanding application need to have, as well as the biological and mechanical characteristics, a high degree of porosity with suitable dimensions for cell seeding and proliferation. Furthermore, the open cell porosity should have adequate interconnectivity for a continuous flow of nutrients and outflow of cell metabolic residues as well as to allow cell growth into confluent layers. Blends of corn starch, a natural biodegradable polymer, with other synthetic polymers (poly(ethylene vinyl alcohol), poly(epsilon-caprolactone), poly(lactic acid)) were selected for this work because of their good balance of properties, namely biocompatibility, processability and mechanical properties. Melt spinning was used to produce fibers from all the blends and 3D meshes from one of the starch-poly(lactic acid) blends. The experimental characterization included the evaluation of the tensile mechanical properties and thermal properties of the fibers and the compression stiffness, porosity and degradation behavior of the 3D meshes. Light microscopy picture of 3D meshes.

Absorption↗
PubMed2004

Bone tissue engineering: state of the art and future trends.

Although several major progresses have been introduced in the field of bone regenerative medicine during the years, current therapies, such as bone grafts, still have many limitations. Moreover, and in spite of the fact that material science technology has resulted in clear improvements in the field of bone substitution medicine, no adequate bone substitute has been developed and hence large bone defects/injuries still represent a major challenge for orthopaedic and reconstructive surgeons. It is in this context that TE has been emerging as a valid approach to the current therapies for bone regeneration/substitution. In contrast to classic biomaterial approach, TE is based on the understanding of tissue formation and regeneration, and aims to induce new functional tissues, rather than just to implant new spare parts. The present review pretends to give an exhaustive overview on all components needed for making bone tissue engineering a successful therapy. It begins by giving the reader a brief background on bone biology, followed by an exhaustive description of all the relevant components on bone TE, going from materials to scaffolds and from cells to tissue engineering strategies, that will lead to "engineered" bone. Scaffolds processed by using a methodology based on extrusion with blowing agents.

Biocompatible Materials↗
PubMed2004

Electrochemical behavior of different preparations of plasma-sprayed hydroxyapatite coatings on Ti6Al4V substrate.

The corrosion behavior of four different preparations of plasma-sprayed hydroxyapatite (HA) coatings on Ti6Al4V substrates in static Hank's balanced salt solution was investigated using dc potentiodynamic and ac impedance techniques. Two different nominal thicknesses, 50 microm and 200 microm, and two different spraying conditions, were considered. The electrochemical impedance experiments proved this technique to be very suitable for the investigation of the electrochemical behavior of surgical implant alloys when they are coated with HA, which is characterized by the dissolution and passivation characteristics of the underlying metal substrate. Because the coatings are porous, ionic paths between the electrolytic medium and the base material can eventually be produced, resulting in the corrosion of the coated metal. Differences in the corrosion resistance of the coated materials were detected, and a relevant model for the description of the coating degradation in the biosimulating solution was proposed. The model consisted of the description of the coated system in terms of a two-layer model of the surface film. Significant differences in electrochemical behavior for similar nominal thicknesses of HA coatings obtained under different spraying conditions were found.

Alloys↗
PubMed2004

Optimization of the formulation and mechanical properties of starch based partially degradable bone cements.

Previous studies have shown the possibility of developing in-situ polymerizable hydrogels that disclose a range of properties that might allow for their use as bone cements. Their main advantage is to be partially degradable, which is important to allow bone ingrowth (better fixation). In addition, their uptake of water makes them less agressive for the tissues, disclosing better fatigue properties and ideal for release of drugs when in service. This work reports a statistical study of the formulation of partially degradable acrylic bone cements that include on their composition corn starch/cellulose acetate blends (SCA). The aim was to optimize a set of properties (mechanical, swelling/degradation and curing) by changing the values of some parameters such as SCA amount and particle size and molar ratio of the acrylic monomers. Statistical tests demonstrated that the most important parameter was the molar ratio of monomers, with the SCA percentage also playing a role. It was possible to develop formulations with mechanical properties in the range of ASTM specifications and with polymerization temperatures lower than those of commercial acrylic cements. Some formulations were subsequently selected for tensile and dynamic mechanical thermal analysis (DMA) tests, under dry and wet conditions.

Biodegradation, Environmental↗
PubMed2004

Hydrophilic matrices to be used as bioactive and degradable bone cements.

Two different hydrophilic systems were investigated regarding their suitability to be used as enzymatically degradable and highly bioactive bone cements. They contained either acrylic acid (AA) or 2-hydroxyethyl methacrylate (HEMA) as the hydrophilic monomer. Swelling, degradation, mechanical and bioactivity tests were employed to characterise their behaviour. Although both of the systems were very hydrophilic, only the one containing HEMA was able to form an apatite-like layer on its surface. Moreover, this system could be degraded by amylolytic enzymes at a rate easily controlled by the incorporation of different amounts of enzyme to the formulation, as shown by the evolution of the mechanical properties, weight loss and glucose concentration in the solution. These results show these novel systems have a great potential to induce bone ingrowth inside the pores created during the degradation of the material, therefore establishing a strong interface with the tissue.

Absorbable Implants↗
PubMed2003

Effect of flow perfusion on the osteogenic differentiation of bone marrow stromal cells cultured on starch-based three-dimensional scaffolds.

This study aims to investigate the effect of culturing conditions (static and flow perfusion) on the proliferation and osteogenic differentiation of rat bone marrow stromal cells seeded on two novel scaffolds exhibiting distinct porous structures. Specifically, scaffolds based on SEVA-C (a blend of starch with ethylene vinyl alcohol) and SPCL (a blend of starch with polycaprolactone) were examined in static and flow perfusion culture. SEVA-C scaffolds were formed using an extrusion process, whereas SPCL scaffolds were obtained by a fiber bonding process. For this purpose, these scaffolds were seeded with marrow stromal cells harvested from femoras and tibias of Wistar rats and cultured in a flow perfusion bioreactor and in 6-well plates for 3, 7, and 15 days. The proliferation and alkaline phosphatase activity patterns were similar for both types of scaffolds and for both culture conditions. However, calcium content analysis revealed a significant enhancement of calcium deposition on both scaffold types cultured under flow perfusion. This observation was confirmed by Von Kossa-stained sections and tetracycline fluorescence. Histological analysis and confocal images of the cultured scaffolds showed a much better distribution of cells within the SPCL scaffolds than the SEVA-C scaffolds, which had limited pore interconnectivity, under flow perfusion conditions. In the scaffolds cultured under static conditions, only a surface layer of cells was observed. These results suggest that flow perfusion culture enhances the osteogenic differentiation of marrow stromal cells and improves their distribution in three-dimensional, starch-based scaffolds. They also indicate that scaffold architecture and especially pore interconnectivity affect the homogeneity of the formed tissue.

Animals↗
PubMed2003

Degradation characteristics of hydroxyapatite coatings on orthopaedic TiAlV in simulated physiological media investigated by electrochemical impedance spectroscopy.

This paper concentrates on the degradation characteristics of hydroxyapatite (HA) coatings on orthopaedic Ti-6Al-4V alloy while immersed in Ringer's salt solution, which were investigated by electrochemical impedance spectroscopy. Electrochemical impedance spectroscopy measurements were used to in situ characterize the electrochemical behavior of the passivated alloy covered with HA during aging in Ringer's solution. Comparison of the electrochemical data for the coated material with that for the uncoated metal substrate was also performed. The characteristic feature that describes the electrochemical behavior of the coated material is the coexistence of large areas of the coating itself with pores where the substrate is exposed to the aggressive media. The interpretation of results was thus performed in terms of a two-layer model of the film, in which the precipitation of hydrated oxide or phosphate compounds seals the pores left by the ceramic coating. The blocking effect due to salt precipitation inside the pores produces an enhancement of the resistance values, thus effectively diminishing the metal ion release in the system.

Alloys↗
PubMed2003

Plasma- and chemical-induced graft polymerization on the surface of starch-based biomaterials aimed at improving cell adhesion and proliferation.

Plasma and chemical induced graft polymerization of acrylic monomers on starch-based biomaterials has been performed with the aim to improve cell adhesion and proliferation on the surface of the polymers, in order to adequate their properties for bone tissue engineering scaffolding applications. Plasma and chemical surface activation was aimed to induce the polymerization of acrylic polar monomers being carried out by applying a radio frequency plasma and expose the samples to a mixture of Ar/O2, or by immersion in a H2O2/(NH4)2S2O8 solution with UV radiation, respectively. Both procedures were followed by the graft polymerization of the corresponding monomers. Polymer grafting was analyzed by Fourier transformed infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) and by contact angle measurements. Properties such as mechanical performance, swelling degree, and degradation behavior, as well as bioactivity, have been studied and compared for the different activation methods. Finally, preliminary cell adhesion and proliferation tests were performed, using goat bone marrow cells, showing a remarkable improvement with respect to original non-surface modified starch-based biomaterials.

Journal Article↗
PubMed2003

Effect of crosslinking, thermal treatment and UV irradiation on the mechanical properties and in vitro degradation behavior of several natural proteins aimed to be used in the biomedical field.

Gelatine (GEL), soy (SI), casein (CAS) and sodium-caseinate (NaCAS) solutions were cast to produce protein films. All the proteins were chemically modified by adding glyoxal to the film-forming solutions in amounts varying from 0 to 0.9% (w/w based on the protein content). After casting, the same films were also submitted to a heat treatment performed at 80 degrees C or UV irradiation. The effect of those chemical/physical modifications on the mechanical properties and on the hydrolytic stability of the protein films was evaluated. As a result, a large variety of protein films with different mechanical properties and degradation profiles were developed. CAS and NaCAS even when chemically/physically modified do not resist to hydrolysis longer than 2 weeks. GEL, only when chemically modified with glyoxal, become water resistant. Due to its hydrolytic stability, SI become a very attractive material for biomedical applications where long term treatments are a requisite.

Journal Article↗