DESARROLLO Y CARACTERIZACION DE CEMENTOS OSEOS MACROPOROSOS DE FOSFATO DE CALCIO

Actualmente, uno de los principales problemas médicos es el incremento del número de pacientes afectados por diversas patologías óseas, como puede ser la pérdida de masa ósea causada por enfermedades, tratamientos quirúrgicos o accidentes. Asimismo, en la población adulta de más de 60 años, cuyo número ha crecido considerablemente con el aumento de la expectativa de vida, se plantean nuevos retos sanitarios ante enfermedades frecuentes en estas edades, como es el caso de la osteoporosis. Si bien estas patologías no son en su mayoría fatales, sí pueden llegar a afectar severamente la calidad de vida de los pacientes al causar cuadros de dolor crónico, incapacidad física o problemas estéticos. En general, el tejido óseo tiene la capacidad de regenerarse para restablecer la continuidad de una zona dañada y satisfacer las funciones de soporte específicas de dicha zona. Sin embargo, no siempre el organismo es capaz de realizar este proceso satisfactoriamente; por ejemplo, cuando se presenta un defecto muy grande o la regeneración tarda largos períodos de tiempo. En otras ocasiones sucede que se hace necesario sustituir el tejido dañado para no perder completamente la funcionalidad en el sitio

The Incorporation of etanercept into a porous tri-layer scaffold for restoring and repairing cartilage tissue

Producción CientíficaCartilage diseases currently affect a high percentage of the world’s population. Almost all of these diseases, such as osteoarthritis (OA), cause inflammation of this soft tissue. However, this could be controlled with biomaterials that act as an anti-inflammatory delivery system, capable of dosing these drugs over time in a specific area. The objective of this study was to incorporate etanercept (ETA) into porous three-layer scaffolds to decrease the inflammatory process in this soft tissue. ETA is a blocker of pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). For this reason, the scaffold was built based on natural polymers, including chitosan and type I collagen. The scaffold was grafted next to subchondral bone using hydroxyapatite as filler. One of the biomaterials obtained was also crosslinked to compare its mechanical properties with the non-treated one. Both samples’ physicochemical properties were studied with SEM, microCT and photoacoustic imaging, and their rheological properties were also compared. The cell viability and proliferation of the human chondrocyte C28/I2 cell line were studied in vitro. An in vitro and in vivo controlled release study was evaluated in both specimens. The ETA anti-inflammatory effect was also studied by in vitro TNF-α and IL-6 production. The crosslinked and non-treated scaffolds had rheological properties suitable for this application. They were non-cytotoxic and favoured the in vitro growth of chondrocytes. The in vitro and in vivo ETA release showed desirable results for a drug delivery system. The TNF-α and IL-6 production assay showed that this drug was effective as an anti-inflammatory agent. In an in vivo OA mice model, safranin-O and fast green staining was carried out. The OA cartilage tissue improved when the scaffold with ETA was grafted in the damaged area. These results demonstrate that this type of biomaterial has high potential for clinical applications in tissue engineering and as a controlled drug delivery system in OA articular cartilage.European Union through the Erasmus PLUS doctoral fellowship (project 2015-1-NL01-KA 107-008639)VIDI personal grant (project 723.012.110

Manufactura y Caracterización de un Biovidrio Sódico-Cálcico para Aplicaciones Clínicas

Soda-lime glasses are characterized by their hardness, brittleness, transparency and high chemical resistance. Moreover, within a certain chemical composition range, these materials (in contact with the body) formed on their surfaces a bone-like apatite layer that induces the implant-tissue chemical bond. In this paper we synthesized a glass with the follow composition, SiO2(52.13%)-Na2O (23.33%)-CaO (22.61%) (wt %). The results obtained by thermal analysis (DTA and TG) showed good correspondence with the parameters (glass transition temperature (Tg) and melting temperature) obtained by hot stage microscopy. In addition, it was found that the material is a bioactive glass (bioglass), due to its sufarce was recovered by a bone-like apatite layer after soaking for different times in simulated body fluid (SBF). This layer had same morphology to those apatite structures reported in the literature formed at similar conditionsLos vidrios sódico-cálcicos se caracterizan por su dureza, fragilidad, transparencia y elevada resistencia química. Por otra parte, dentro de un determinado intervalo de composición química, estos materiales al estar en contacto con el organismo forman sobre sus superficies una capa de apatita que favorece la unión química implante-tejido. En el presente trabajo se sintetizó un vidrio de composición, SiO2 (52.13 %)-Na2O (23.33 %)-CaO (22.61 %) (% en masa). Los resultados obtenidos por las técnicas de análisis térmico (ATD y TG) están en concordancia con aquellos obtenidos por microscopía óptica de calefacción (temperatura de transición vítrea (Tg) y temperatura de fusión). Además se comprobó que el material en estudio es un vidrio con propiedades bioactivas (biovidrio) ya que se formó sobre su superficie una capa de fosfato de calcio tipo apatita luego de interactuar con el fluido biológico simulado (SBF)

Cemento de β-Silicato Dicálcico para Aplicaciones Biomédicas

β-dicalcium silicate (β-Ca2SiO_4, β-C_2S) is one of the main constituents in Portland cement clinker and many refractory materials, itself is a hydraulic cement that reacts with water or aqueous solution at room/body temperature to form a hydrated phase (C-S-H), which provides mechanical strength to the end product. In the present investigation β-C_2S was synthesized by sol-gel process and it was used as powder to cement preparation, named CSC. Biodegradation and citotoxicity studies were assessed to cement samples. Sol-gel process is an available synthesis method in order to obtain a pure powder of β-C_2S at relatively low temperatures without chemical stabilizers. A bone-like apatite layer covered the material surface after soaking in SBF and its compressive strength (CSC cement) was comparable with that of the trabecular bone. The cement showed a non cytotoxic response against cells culture and presented high values of cellular viability.El β-silicato dicálcico (β-Ca2SiO_4, β-C_2S) es uno de los principales constituyentes del cemento Portland y de muchos materiales refractarios. Es un cemento hidráulico que fragua formando una fase hidratada del tipo C-S-H que ofrece resistencia mecánica al material final. El β-C_2S se sintetizó vía sol-gel empleado como fase sólida en la preparación de un cemento denominado CSC. Además se realizaron estudios de biodegradación y citotoxicidad al cemento. La síntesis sol-gel resultó ser una alternativa viable frente a las tradicionales síntesis al estado sólido obteniéndose el polvo de β-C_2S con excelente pureza y sin el empleo de estabilizadores químicos. Luego de la inmersión en SBF la superficie de CSC quedó recubierta por una capa de hidroxiapatita deficiente en calcio presentando el material una resistencia a la compresión comparable a la del hueso trabecular. El cemento mostró un comportamiento no citotóxico frente al cultivo celular y presentó elevados valores de viabilidad celular

The Effects of crosslinking on the rheology and cellular behavior of polymer-based 3D-multilayered scaffolds for restoring articular cartilage

Producción CientíficaPolymer-based tri-layered (bone, intermediate and top layers) scaffolds used for the restoration of articular cartilage were prepared and characterized in this study to emulate the concentration gradient of cartilage. The scaffolds were physically or chemically crosslinked. In order to obtain adequate scaffolds for the intended application, the impact of the type of calcium phosphate used in the bone layer, the polymer used in the intermediate layer and the interlayer crosslinking process were analyzed. The correlation among SEM micrographs, physical-chemical characterization, swelling behavior, rheological measurements and cell studies were examined. Storage moduli at 1 Hz were 0.3–1.7 kPa for physically crosslinked scaffolds, and 4–5 kPa (EDC/NHS system) and 15–20 kPa (glutaraldehyde) for chemically crosslinked scaffolds. Intrinsic viscoelasticity and poroelasticity were considered in discussing the physical mechanism dominating in different time/frequency scales. Cell evaluation showed that all samples are available as alternatives to repair and/or substitute cartilage in articular osteoarthritis.The European Union through the Erasmus MUNDUS LINDO post-doctoral fellowship,(project code ML14PD1157) and Erasmus PLUS doctoral fellowship, (project code 2015-1-NL01-KA 107-008639)European Union’s Horizon 2020 research and innovation program. grant agreement - H2020- MSCA-RISE (644373—PRISAR), H2020-MSCA-RISE (777682—CANCER), H2020-WIDESPREAD-05- 2017-Twinning (807281—ACORN), H2020-WIDESPREAD-2018-03 (852985—SIMICA), H2020-SCA RISE-2016 (734684—CHARMED) and MSCA-ITN-2015-ETN (675743—ISPIC), 861190 (PAVE), 857894 (CAST), 859908 (NOVA-MRI); 872860 (PRISAR2)VIDI grant (project number 723.012.110

Thermosensitive Injectable Hydrogels for Intra-Articular Delivery of Etanercept for the Treatment of Osteoarthritis

The intra-articular administration of drugs has attracted great interest in recent decades for the treatment of osteoarthritis. The use of modified drugs has also attracted interest in recent years because their intra-articular administration has demonstrated encouraging results. The objective of this work was to prepare injectable-thermosensitive hydrogels for the intra-articular administration of Etanercept (ETA), an inhibitor of tumor necrosis factor-α. Hydrogels were prepared from the physical mixture of chitosan and Pluronic F127 with β-glycerolphosphate (BGP). Adding β-glycerolphosphate to the system reduced the gelation time and also modified the morphology of the resulting material. In vitro studies were carried out to determine the cytocompatibility of the prepared hydrogels for the human chondrocyte line C28/I2. The in vitro release study showed that the incorporation of BGP into the system markedly modified the release of ETA. In the in vivo studies, it was verified that the hydrogels remained inside the implantation site in the joint until the end of the study. Furthermore, ETA was highly concentrated in the blood of the study mice 48 h after the loaded material was injected. Histological investigation of osteoarthritic knees showed that the material promotes cartilage recovery in osteoarthritic mice. The results demonstrate the potential of ETA-loaded injectable hydrogels for the localized treatment of joints

A novel information criterion to elucidate a drug delivery mechanism from poly (acrylamide-co-2-hydroxyethyl methacrylate) reinforced with hydroxyapatite composite

Producción CientíficaHydrophilic composites of poly (acrylamide-co-2-hydroxyethyl methacrylate) reinforced with hydroxyapatite were synthesized, characterized and evaluated as drug delivery systems. The results show a strong dependence of the polymer composition, the degree of crosslinking and the homogeneity of the particles dispersion (filler or the mixed drug) in the characteristics that were analyzed. The mechanical properties were better while the swelling and the diffusion coefficient were worse than hydrogels with cefazolin of similar compositions. Additionally, a new information criterion was used to elucidate the best fit. The drug diffusion into the medium was anomalous with a tendency towards Case II transport, indicating that under certain conditions zero-order diffusion could be achieved. This fact suggests that these materials could be used in the manufacture of medical devices for the controlled delivery of drugs and active or biological principles, significantly improving therapeutic procedures today.2020-12-062020-12-06European Union (Erasmus PLUS project NL01-KA 107-008639; Erasmus MUNDUS LINDO ML14PD1157