Grupos Investigadores

Miembros del Grupo

Bikuña Izaqirre
Norma Camila
Vesga Castro
Andrés Felipe
Zemanate Largo

Líneas de Investigación

  • Caracterización mecánica de scaffolds y biomateriales
  • Diseño y modelización de scaffolds
  • Fabricación de scaffolds por electrospinning y bioimpresión

Palabras Clave

  • Bioimpresión
  • Caracterización mecánica
  • Electrospinning
  • Fabricación
  • Ingeniería de tejidos
  • Mecanotransducción
  • Scaffolds

Publicaciones Científicas desde 2018

  • Autores: Bikuna-Izagirre, M.; Aldazábal Mensa, Javier; Extramiana, L.; et al.
    ISSN: 2373-9878 Vol.9 N° 11 2023 págs. 6333 - 6344
    Primary open-angle glaucoma is characterized by the progressive degeneration of the optic nerve, with the high intraocular pressure (IOP) being one of the main risk factors. The human trabecular meshwork (HTM), specifically the juxtacanalicular tissue (JCT), is responsible for placing resistance to the aqueous humor (AH) outflow and the resulting IOP control. Currently, the lack of a proper in vitro JCT model and the complexity of three-dimensional models impede advances in understanding the relationship between AH outflow and HTM degeneration. Therefore, we design an in vitro JCT model using a polycaprolactone (PCL) nanofibrous scaffold, which supports cells to recapitulate the functional JCT morphology and allow the study of outflow physiology. Mechanical and morphological characterizations of the electrospun membranes were performed, and human trabecular meshwork cells were seeded over the scaffolds. The engineered JCT was characterized by scanning electron microscopy, quantitative real-time polymerase chain reaction, and immunochemistry assays staining HTM cell markers and proteins. A pressure-sensitive perfusion system was constructed and used for the investigation of the outflow facility of the polymeric scaffold treated with dexamethasone (a glucocorticoid) and netarsudil (a novel IOP lowering the rho inhibitor). Cells in the in vitro model exhibited an HTM-like morphology, expression of myocilin, fibronectin, and collagen IV, genetic expression, outflow characteristics, and drug responsiveness. Altogether, the present work develops an in vitro JCT model to better understand HTM cell biology and the relationship between the AH outflow and the HTM and allow further drug screening of pharmacological agents that affect the trabecular outflow facility.
  • Autores: Bikuña Izagirre, M.; Aldazábal Mensa, Javier; Moreno Montañés, Javier; et al.
    ISSN: 1937-3341 Vol.29 N° 13 - 14 2023
  • Autores: Bikuna-Izagirre, M.; Aldazábal Mensa, Javier; Extramiana, L.; et al.
    ISSN: 0006-3592 Vol.119 N° 10 2022 págs. 2698 - 2714
    Glaucoma is the leading cause of irreversible blindness worldwide and is characterized by the progressive degeneration of the optic nerve. Intraocular pressure (IOP), which is considered to be the main risk factor for glaucoma development, builds up in response to the resistance (resistance to what?) provided by the trabecular meshwork (TM) to aqueous humor (AH) outflow. Although the TM and its relationship to AH outflow have remained at the forefront of scientific interest, researchers remain uncertain regarding which mechanisms drive the deterioration of the TM. Current tissue-engineering fabrication techniques have come up with promising approaches to successfully recreate the TM. Nonetheless, more accurate models are needed to understand the factors that make glaucoma arise. In this review, we provide a chronological evaluation of the technological milestones that have taken place in the field of glaucoma research, and we conduct a comprehensive comparison of available TM fabrication technologies. Additionally, we also discuss AH perfusion platforms, since they are essential for the validation of these scaffolds, as well as pressure-outflow relationship studies and the discovery of new IOP-reduction therapies.
  • Autores: Vesga-Castro, C.; Aldazábal Mensa, Javier; Vallejo-Illarramendi, A. (Autor de correspondencia); et al.
    Revista: ELIFE
    ISSN: 2050-084X Vol.11 2022 págs. e77204
    Over the last few years, there has been growing interest in measuring the contractile force (CF) of engineered muscle tissues to evaluate their functionality. However, there are still no standards available for selecting the most suitable experimental platform, measuring system, culture protocol, or stimulation patterns. Consequently, the high variability of published data hinders any comparison between different studies. We have identified that cantilever deflection, post deflection, and force transducers are the most commonly used configurations for CF assessment in 2D and 3D models. Additionally, we have discussed the most relevant emerging technologies that would greatly complement CF evaluation with intracellular and localized analysis. This review provides a comprehensive analysis of the most significant advances in CF evaluation and its critical parameters. In order to compare contractile performance across experimental platforms, we have used the specific force (sF, kN/m(2)), CF normalized to the calculated cross-sectional area (CSA). However, this parameter presents a high variability throughout the different studies, which indicates the need to identify additional parameters and complementary analysis suitable for proper comparison. We propose that future contractility studies in skeletal muscle constructs report detailed information about construct size, contractile area, maturity level, sarcomere length, and, ideally, the tetanus-to-twitch ratio. These studies will hopefully shed light on the relative impact of these variables on muscle force performance of engineered muscle constructs. Prospective advances in muscle tissue engineering, particularly in muscle disease models, will require a joint effort to develop standardized methodologies for assessing CF of engineered muscle tissues.
  • Autores: Andreu Arzuaga, Ion (Autor de correspondencia); Granero-Moya, I.; Chahare, N. R.; et al.
    ISSN: 1465-7392 Vol.24 N° 6 2022 págs. 896
    Mechanical force controls fundamental cellular processes in health and disease, and increasing evidence shows that the nucleus both experiences and senses applied forces. Such forces can lead to the nuclear translocation of proteins, but whether force controls nucleocytoplasmic transport, and how, remains unknown. Here we show that nuclear forces differentially control passive and facilitated nucleocytoplasmic transport, setting the rules for the mechanosensitivity of shuttling proteins. We demonstrate that nuclear force increases permeability across nuclear pore complexes, with a dependence on molecular weight that is stronger for passive than for facilitated diffusion. Owing to this differential effect, force leads to the translocation of cargoes into or out of the nucleus within a given range of molecular weight and affinity for nuclear transport receptors. Further, we show that the mechanosensitivity of several transcriptional regulators can be both explained by this mechanism and engineered exogenously by introducing appropriate nuclear localization signals. Our work unveils a mechanism of mechanically induced signalling, probably operating in parallel with others, with potential applicability across signalling pathways. Andreu et al. show that force regulates nucleocytoplasmic transport by weakening the permeability barrier of nuclear pore complexes, affecting passive and facilitated diffusion in different ways.
  • Autores: Bikuna-Izagirre, M.; Aldazábal Mensa, Javier; Paredes Puente, Jacobo (Autor de correspondencia)
    Revista: POLYMERS
    ISSN: 2073-4360 Vol.14 N° 7 2022 págs. 1311
    The electrospinning of hybrid polymers is a versatile fabrication technique which takes advantage of the biological properties of natural polymers and the mechanical properties of synthetic polymers. However, the literature is scarce when it comes to comparisons of blends regarding coatings and the improvements offered thereby in terms of cellular performance. To address this, in the present study, nanofibrous electrospun scaffolds of polycaprolactone (PCL), their coating and their blend with gelatin were compared. The morphology of nanofibrous scaffolds was analyzed under field emission scanning electron microscopy (FE-SEM), indicating the influence of the presence of gelatin. The scaffolds were mechanically tested with tensile tests; PCL and PCL gelatin coated scaffolds showed higher elastic moduli than PCL/gelatin meshes. Viability of mouse embryonic fibroblasts (MEF) was evaluated by MTT assay, and cell proliferation on the scaffold was confirmed by fluorescence staining. The positive results of the MTT assay and cell growth indicated that the scaffolds of PCL/gelatin excelled in comparison to other scaffolds, and may serve as good candidates for tissue engineering applications.
  • Autores: Paredes Puente, Jacobo; Cortizo-Lacalle, D.; Imaz, A.; et al.
    ISSN: 2045-2322 Vol.12 N° 1 2022 págs. 3898
    Mechanical characterization supposes a key step in the development of cultured meat to help mimicking the sensorial properties of already existing commercial products based on traditional meat. This work presents two well stablished methods that can help studying cultured meat mechanical characteristics: texture profile analysis (double compression test) and rheology. These techniques provide data about the elastic and viscous behaviour of the samples but also values about other texture characteristics such as springiness, cohesiveness, chewiness and resilience. In this work, we present a comparison of cultured meat-based samples with commercial of the shelf common meat products (sausage, turkey and chicken breast). Results show that both Young¿s and Shear modulus in the cultured meat samples can be compared to commercial products in order to understand its properties. The texture characteristics for the cultured meat studied, show values within the range of commercial products. These results demonstrate the applicability of this methodology for the adjustment of mechanical properties of cultured meat products
  • Autores: Chiesa-Estomba, C. M.; Hernaez-Moya, R.; Rodino, C.; et al.
    Revista: CARTILAGE
    ISSN: 1947-6035 Vol.13 N° 4 2022 págs. 105 - 118
    Objective The surgical management of nasal septal defects due to perforations, malformations, congenital cartilage absence, traumatic defects, or tumors would benefit from availability of optimally matured septal cartilage substitutes. Here, we aimed to improve in vitro maturation of 3-dimensional (3D)-printed, cell-laden polycaprolactone (PCL)-based scaffolds and test their in vivo performance in a rabbit auricular cartilage model. Design Rabbit auricular chondrocytes were isolated, cultured, and seeded on 3D-printed PCL scaffolds. The scaffolds were cultured for 21 days in vitro under standard culture media and normoxia or in prochondrogenic and hypoxia conditions, respectively. Cell-laden scaffolds (as well as acellular controls) were implanted into perichondrium pockets of New Zealand white rabbit ears (N = 5 per group) and followed up for 12 weeks. At study end point, the tissue-engineered scaffolds were extracted and tested by histological, immunohistochemical, mechanical, and biochemical assays. Results Scaffolds previously matured in vitro under prochondrogenic hypoxic conditions showed superior mechanical properties as well as improved patterns of cartilage matrix deposition, chondrogenic gene expression (COL1A1, COL2A1, ACAN, SOX9, COL10A1), and proteoglycan production in vivo, compared with scaffolds cultured in standard conditions. Conclusions In vitro maturation of engineered cartilage scaffolds under prochondrogenic conditions that better mimic the in vivo environment may be beneficial to improve functional properties of the engineered grafts. The proposed maturation strategy may also be of use for other tissue-engineered constructs and may ultimately impact survival and integration of the grafts in the damaged tissue microenvironment.
  • Autores: Garate, U.; Mardaras, E.; González, R.; et al.
    Revista: METALS
    ISSN: 2075-4701 Vol.12 N° 6 2022 págs. 1047
    A multilayer laser-deposited lining of AISI 316L stainless steel makes a regular structural steel surface corrosion resistant in physiological media. Despite the application of single-layer stainless-steel linings being economically beneficial and allowing thinner surface modifications, dilution effects that modify the pitting resistance of the coating must be accounted for. In order to study the feasibility of employing single-layer coatings instead of multilayer coatings for corrosion protection in physiological media, a polarization testing back-to-back comparison was performed between laser-deposited AISI 316L monolayers on 42CrMo4 quenched and tempered steel and cold-rolled AISI 316L sheet in Dulbecco's Phosphate Buffer Solution at 36 degrees C. A higher dispersion in pitting resistance, ranging from 800 mV to 1200 mV, was found on the coated samples, whereas the cold-rolled material was more stable in the 1200 mV range. The resulting differences in corrosion rates and pitting potentials open the discussion on whether the chemical composition deviations on AISI 316L dilution layers are acceptable in terms of surface functionality in medical devices.
  • Autores: Moreno Montañés, Javier; Extramiana, L.; Bikuña, M.; et al.
    ISSN: 0146-0404 Vol.63 N° 7 2022
  • Autores: Chiesa-Estomba, C. M.; Aiastui, A.; González-Fernández, I.; et al.
    ISSN: 1738-2696 Vol.18 N° 3 2021 págs. 343 - 353
    BACKGROUND: In recent years, three-dimensional (3D)-printing of tissue-engineered cartilaginous scaffolds is intended to close the surgical gap and provide bio-printed tissue designed to fit the specific geometric and functional requirements of each cartilage defect, avoiding donor site morbidity and offering a personalizing therapy. METHODS: To investigate the role of 3D-bioprinting scaffolding for nasal cartilage defects repair a systematic review of the electronic databases for 3D-Bioprinting articles pertaining to nasal cartilage bio-modelling was performed. The primary focus was to investigate cellular source, type of scaffold utilization, biochemical evaluation, histological analysis, in-vitro study, in-vivo study, animal model used, length of research, and placement of experimental construct and translational investigation. RESULTS: From 1011 publications, 16 studies were kept for analysis. About cellular sources described, most studies used primary chondrocyte cultures. The cartilage used for cell isolation was mostly nasal septum. The most common biomaterial used for scaffold creation was polycaprolactone alone or in combination. About mechanical evaluation, we found a high heterogeneity, making it difficult to extract any solid conclusion. Regarding biological and histological characteristics of each scaffold, we found that the expression of collagen type I, collagen Type II and other ECM components were the most common patterns evaluated through immunohistochemistry on in-vitro and in-vivo studies. Only two studies made an orthotopic placement of the scaffolds. However, in none of the studies analyzed, the scaffold was placed in a subperichondrial pocket to rigorously simulate the cartilage environment. In contrast, scaffolds were implanted in a subcutaneous plane in almost all of the studies included. CONCLUSION: The role of 3D-bioprinting scaffolding for nasal cartilage defects repair is growing field. Despite the amount of information collected in the last years and the first surgical applications described recently in humans. Further investigations are needed due to the heterogeneity on mechanical evaluation parameters, the high level of heterotopic scaffold implantation and the need for quantitative histological data.
  • Autores: Stephens, M.; López-Linares, K.; Aldazábal Mensa, Javier; et al.
    ISSN: 2052-4463 Vol.8 N° 1 2021 págs. 240
    The development of new effective and safer therapies for osteoporosis, in addition to improved diagnostic and prevention strategies, represents a serious need in the scientific community. Micro-CT image-based analyses in association with biomechanical testing have become pivotal tools in identifying osteoporosis in animal models by assessment of bone microarchitecture and resistance, as well as bone strength. Here, we describe a dataset of micro-CT scans and reconstructions of 15 whole femurs and biomechanical tests on contralateral femurs from C57BL/6JOlaHsd ovariectomized (OVX), resembling human post-menopausal osteoporosis, and sham operated (sham) female mice. Data provided for each mouse include: the acquisition images (.tiff), the reconstructed images (.bmp) and an.xls file containing the maximum attenuations for each reconstructed image. Biomechanical data include an.xls file with the recorded load-displacement, a movie with the filmed test and an.xls file collecting all biomechanical results.
  • Autores: Aldazábal Mensa, Javier (Autor de correspondencia); Bergara, A.; Stephen, M.; et al.
    ISSN: 2792-4246 Vol.2 2021 págs. 15 - 19
    La determinación de la carga capaz de soportar un hueso se puede medir experimentalmente, en principio, mediante un ensayo de tracción convencional. Sin embargo, y dada la compleja geometría del hueso, así como las dificultades para su fijación en una máquina de tracción hace muy difícil la medida directa de la tensión de rotura mismo. Estas dificultades hacen que sea frecuente la determinación de las propiedades de dichos materiales mediante ensayos de flexión en 3 puntos. Para determinar las propiedades mecánicas de los huesos mediante ensayos de flexión requiere del conocimiento no solo de los registros carga-desplazamiento obtenidos durante los ensayos sino también de la geometría de estos. En este trabajo se ha propone un método para determinar las propiedades mecánicas de huesos combinando ensayos mecánicos con técnicas de micro-tomografía computarizada. En este trabajo se ha realizado un ensayo bio-mecánico sobre un fémur de ratón del cual se conocía previamente su geometría. Dado el carácter frágil del hueso se ha supuesto un comportamiento elástico-lineal del mismo hasta el fallo. Una vez realizado el ensayo se ha determinado, a partir de la carga máxima alcanzada, la tensión máxima real que ha soportado empleando tanto las teorías clásicas de resistencia de materiales de vigas como técnicas de elementos finitos. Como resultado de este trabajo se muestra la comparación entre los resultados obtenidos mediante la teoría de vigas, fácil de aplicar, y los modelos de elem
  • Autores: Artola, G. (Autor de correspondencia); Aldazábal Mensa, Javier
    ISSN: 0034-8570 Vol.57 N° 3 2021 págs. e198
    Different hydrogen-induced cracking patterns have been observed on two construction steels belonging to the same strength grade for mooring offshore structures, when tested in a Slow Strain Rate Tensile test (SSRT) condition. A scenario is hypothesized, in which this behaviour arises from differences in hydrogen trapping capacity between the two steels. A novel finite difference modelling approach is proposed to assess the plausibility of this hypothesis. The model is designed to resemble the effect of the diffusible and the trapped hydrogen in the nucleation and growth of cracks during SSRT, and consequently in life service. The effect of different hydrogen trapping capacities has been simulated employing the proposed stress-diffusion-strength model. A higher content in traps led to fewer cracks; while the absence of traps led to a higher number of cracks. These results fit with the hypothesis, as variations in trapping capacity lead to variations in the number of cracks.
  • Autores: Artola, G.; Aldazábal Mensa, Javier
    Revista: METALS
    ISSN: 2075-4701 Vol.10 N° 12 2020 págs. 1613
    When steel components fail in service due to the intervention of hydrogen assisted cracking, discussion of the root cause arises. The failure is frequently blamed on component design, working conditions, the manufacturing process, or the raw material. This work studies the influence of quench and tempering and hot-dip galvanizing on the hydrogen embrittlement behavior of a high strength steel. Slow strain rate tensile testing has been employed to assess this influence. Two sets of specimens have been tested, both in air and immersed in synthetic seawater, at three process steps: in the delivery condition of the raw material, after heat treatment and after heat treatment plus hot-dip galvanizing. One of the specimen sets has been tested without further manipulation and the other set has been tested after applying a hydrogen effusion treatment. The outcome, for this case study, is that fracture risk issues only arise due to hydrogen re-embrittlement in wet service.
  • Autores: Gil Sevillano, Javier (Autor de correspondencia); Aldazabal, I.; Aldazábal Mensa, Javier
    Revista: METALS
    ISSN: 2075-4701 Vol.10 N° 12 2020 págs. 1649
    Volume changes accompanying the plastic deformation at 300 K of nanocrystalline samples of alpha-Fe with a columnar grain structure possessing a < 1 (1) over bar0 > random fiber texture has been obtained from molecular dynamics (MD) simulations. The samples were strained in tension along the common axial direction of the columnar grains. After removal of the elastic volume change, the evolution of plastic volume strain was obtained. Small but non-negligible volume dilations or contractions are observed depending on size (samples of very small grain size show volume contraction). The rate of volume change is high during the first 10% plastic deformation and continues at a low pace thereafter; the first 10% deformation represents a transient in the stress-strain behavior too. The complex behavior observed is reasonably explained by the superposition of contributions from different plastically-induced structural changes to the mass density change: Mainly from changes of grain size, grain boundary structure, dislocation density and density of point-defects. The results are of interest for the development of crystal plasticity theories not restricted by the volume conserving assumption.

Proyectos desde 2018

  • Título: Microscopio Confocal espectral con superresolución hasta 120nm
    Código de expediente: 2022-CIEN-000026-01
    Investigador principal: JACOBO PAREDES PUENTE.
    Convocatoria: R.C.T.I. Proyectos de inversión en equipamiento e infraestructuras científico tecnológicas
    Fecha de inicio: 01-09-2022
    Fecha fin: 30-09-2023
    Importe concedido: 100.000,00€
    Otros fondos: -
  • Título: Optimización de los parámetros de estimulación mecánica para el desarrollo y la maduración de orgánulos musculares in vitro en 3D. (OptiMUS)
    Código de expediente: PIBA_2022_1_0020
    Financiador: GOBIERNO VASCO
    Fecha de inicio: 11-08-2022
    Fecha fin: 30-06-2025
    Importe concedido: 0
    Otros fondos: -
  • Título: Identificación de nuevas dianas para el tratamiento del glaucoma basados en los cambios biofísicos y presión intraocular sobre las HTMC en un modelo 3D de malla trabecular.
    Código de expediente: PI18/01782
    Convocatoria: AES2018 PI
    Fecha de inicio: 01-01-2019
    Fecha fin: 30-06-2023
    Importe concedido: 154.880,00€
    Otros fondos: Fondos FEDER
    Investigador principal: JACOBO PAREDES PUENTE
    Fecha de inicio: 01-01-2020
    Fecha fin: 30-06-2020
    Importe: 0
    Otros fondos: -