NM4BL2021

Proteins are the most versatile biological building blocks composed of smaller units, amino acids which offer a rich chemistry. Proteins present enormous diversity in 3D structures that translates into amazing functional diversity. Thus, proteins have great potential for their use as building blocks to construct tailored designed systems, including nanofabrication and generation of novel protein-based functional biomaterials.

We explore the potential of engineered proteins as building blocks toward the generation of functional nanostructures and bioinspired materials for applications in a broad range of applications, both technological and biomedical. In particular, our main objective is to develop versatile platforms based on simple protein building blocks for the fabrication of multiple protein-based hybrid functional nanostructures and biomaterials.

Several examples will be shown to illustrate the potential of those engineered protein-based systems in catalysis, bioelectronics, biosensing and disease treatment and diagnosis.

Introduction:
The generation of human pluripotent stem cells (hPSCs) derived organoids is one of the biggest scientific advances to understand how human tissues develop and how these get disease.
Methods/Results:
hPSCs were exposed to three-dimensional microenvironment culture conditions forcing cell-to-cell contact and cell to extracellular matrix (ECM) interactions in the presence of defined renal inductive signals to generate kidney organoids. Our approach led to the generation of kidney organoids that transcriptomically match second-trimester human fetal kidneys. We then developed a transplantation method that exploits the intrinsic properties of the chick chorioallantoic membrane (CAM) to recreate a soft in vivo microenvironment for organoid growth and differentiation, including vascularization in vivo. We have also shown that the emulation of the mechanical properties of the native kidney enhances differentiation in hPSCs-kidney organoids. All in all, these tools have allowed us to exploit our organoid platforms to study first steps of SARS-CoV-2 infection validating the use of a therapeutic compound decreasing viral load. Now, we are exploring on the interaction of systemic conditions impacting on kidney function and disease. Specifically, we are addressing on how a diabetic-like microenvironment impacts on SARS-CoV-2 infection.

The development of in vitro cell culture systems that better mimic the interactions that take place between cells and the extracellular matrix (ECM) in live organs and tissues has become a priority for research in human health and the pharmaceutical industry. In the context of regenerative medicine, the combination of human stem cells with cell therapy suited ECMs that provide an adequate 3D bioinductive support for the personalised generation of autologous tissues holds an extraordinary relevance, and could constitute a breakthrough to treat so far incurable lesions and diseases. Modern decellularisation technologies allow obtaining high amounts of biocompatible ECMs from diverse tissues of both animal and human origin. Decellularised Adipose Tissue (DAT) constitutes a high-quality ECM rich in collagen and adhesion proteins, which can be formulated with different physical textures and incorporated to any cell culture device. In this talk I will highlight our work using porcine and human-derived solid-foam DAT for the long-term culture of human Dental Pulp Stem Cells (hDPSCs), to promote their osteodifferentiation and bone generation in vitro. I will end up discussing the possibilities of application of DAT-hDPSC cultures for the (re)generation of vascular and neural tissues.

The neuronal doctrine favored by Ramon y Cajal, the founder of modern neuroscience, relied on the development of a histological technique, Golgi staining, that allowed the visualization of cell bodies in the brain. Thus, ever since its inception, major advances in Neuroscience have been possible through the development of new experimental tools. Opto- and chemo-genetics, fiber photometry, microfluidics…etc are current examples. Biological-compatible materials constitute an exciting addition to the technological armamentarium in our discipline. Biomaterials are used for two main purposes, 1) develop new tools that will allow the study of brain function at an unprecedented level (i.e.: single-cell chronic electrodes, organoids…etc), and 2) generate novel diagnostics, biomarkers, and even therapies. At Achucarro, we are interested in both types of approaches. We count on the properties of Janus magnetic nanoparticles to develop new means to manipulate and visualize microglia, the immune cell of the brain. We think of functionalized magnetic nanoparticles to visualize blood-brain-barrier and neuroprotective activity of insulin hormones. We need novel materials to support in vitro growth in 2D and 3D conditions (matrices) of human iPSC-derived neurons to generate human models of disease. The latter adds to the development of in vitro organoids derived from human cells using “organ-on-chip” approaches that require novel materials such as hydrogels and bio-sensors to maintain physiological conditions. Multimodal imaging using lipid-based nanoparticles is also a new diagnostic tool directed to different types of brain traumas. A fluid interaction with material scientists is therefore a must for Achucarro and we have placed it as a strategic priority in our current research project.

Precision, or personalised medicine aims to improve life quality by tailoring diagnostics, medical treatment and patient follow-up to the specific needs of individuals. New advanced materials and processes, at the heart of this revolution, are enabling progress and advances at an unprecedented pace.

In this talk, we will show three areas where BCMaterials contributes with advanced materials for sensors and biosensors, tissue engineering and organ-on-a-chip devices. These materials and devices support different sides of personalised medicine, from early personalized diagnostics, to personalized tissue engineering, to home and personal analytics for treatment control.

El advenimiento de las tecnologías de fabricación aditiva a la ingeniería de tejidos vivos ha facilitado la entrada en el campo de grupos de investigación provenientes del ámbito de los biomateriales, de manera que actualmente estamos en plena (r)evolución en las maneras de hacer organoides, organs-on-chip, epitelios sencillos y, quizá en un futuro, imitaciones más o menos relevantes de órganos y tejidos más complejos. Sin embargo, los biomateriales y las biotintas para impresión 3D generalmente se diseñan intentando imitar las propiedades de rigidez y porosidad del tejido nativo, y que por supuesto permitan la adhesión y supervivencia celular. En esta charla describiré (desde el punto de vista de un biólogo celular con cierta experiencia en células madre adultas y el control de la diferenciación celular) por qué esta aproximación está condenada al fracaso y debemos sofisticar la utilización de biomateriales en sustitutos de órganos y tejidos para poder dirigir la diferenciación celular de manera guiada. Utilizaré como ejemplo el uso de matrices extracelulares descelularizadas obtenidas de órganos nativos.

The rapid test sector has undergone a considerable boost during the last years due to the need for diagnostic methods offering results in just a few minutes. It has been clearly seen during the pandemic, where the high demand of both serological and antigen tests has significantly increased the development of lateral flow test.
However, all these tests are associated with the use of a large amount of plastic materials. In order to minimize the use of plastics, a new porous material has been developed, using cellulose derivatives and inorganic compounds. In order to industrialize this material, a printable aqueous formulation for paper-based substrates has been developed, so that it can replace the traditional nitrocellulose material used in these kind of tests. A proof of concept for the application of these materials in the development of lateral flow test based on immunological reactions will be presented.

El desarrollo de nuevos materiales destinados a aplicaciones biomédicas y biotecnológicas no solo conlleva una serie de desafíos técnicos, sino que también debe ir acompañado de una reflexión sobre los desafíos regulatorios a los que este material se va a enfrentar en el futuro. Conocer la regulación actual y pruebas a las que el material se va a tener que someter puede ser crucial para toma de decisiones acertadas a lo largo del desarrollo de un material. El objetivo de esta charla será informar sobre algunos de los ensayos a los que un biomaterial se puede tener que enfrentar, y más concretamente sobre los ensayos que podemos llevar a cabo en el centro tecnológico Gaiker, donde llevamos muchos años poniendo a punto y realizando estudios in vitro de eficacia y seguridad de fármacos y dispositivos médicos.

BioDyce is an integrated system of bioreactors & scaffolds, with peripheral modules, to expand its active performance, designed especially for smart scaffolds as active actuators. They act as static or dynamic supports for the cells allowing to provide a variety of highly controlled dynamic stimulations. With this approach, BioDyce improves the development cellular proliferation and differentiation by mimicking the human body. In this context, BioDyce aims to address this unmet need allowing to faithfully recreate in-vitro the physiological complexity of tissues and organs.

ABSTRACT: The talk will be focused on Tecnalia experience in a field of Multi Array Biomedical Electrodes describing the applied R&D process for selected demonstrators with their technologies, materials, prototypes and related laboratory, clinical and real life validation procedures.