Traditionally, the mammalian heart has been considered a post-mitotic terminally differentiated organ. It was believed that cardiomyocytes present at birth would persist, without further division, throughout the entire organism life. Consequently, upon injury, such as the one produced by a myocardial infarction, cardiac tissue is not able to regenerate. The scar formed interferes with the normal heart functioning, leading to organ failure.
Recently, the identification and characterization of resident cardiac stem cells (CSCs) changed the paradigms towards cardiac regeneration. Data support that activation of cell molecular machinery can result in cardiomyocyte dedifferentiation and improved heart functionality. These findings open the possibility of heart self-healing in response to specific stimuli after infarction.
Given the prospect of true myocardial regeneration, new strategies to induce in situ cell activation sources with myogenic and angiogenic properties is a great opportunity for myocardial tissue regeneration. This project proposes an original strategy towards in situ cardiac tissue regeneration that relies on novel biomaterials (Organogels). Preliminary data support that these biomaterials possess unique physicochemical properties resulting in chemotactic cell attraction, activation and vascularization at the infarcted tissue. The project will explore this strategy as a novel way of in vivo cardiomyocyte reprogramming system.
This project will be carried out in collaboration between IBEC groups of “Biomaterials for Regenerative Therapies” and “Biomimetic systems for cell engineering”. Both groups work at the interface between material science, microengineering, cell biology and material-cell interface. They combine cutting edge engineering techniques (3D bioprinting, electrospinning, microfabrication, microfluidics, multistimuli bioreactors) with cell biological models (stem cells, organoids and spheroids) aiming new strategies in regenerative medicine.
The person involved in this project will have the opportunity to be immersed in the field of tissue engineering by working on the design and fabrication of a novel biomaterial with the requirements needed for promoting heart regeneration in situ. Innovative technologies based on 3D printing and bioprinting will be the core of his/her research to produce appropriate materials that will create a specific environment to control scar formation and cardiac tissue regeneration after ischemia.
Cell culture and biochemistry techniques will also be part of his/her work, in order to characterize the obtained biomaterial and better define its properties. The new concept of in situ cardiac regeneration would be tested in in vitro systems, which model cardiac tissue surrogates (microengineered tissues and cardiac spheroids), and in in vivo models. Thus, the student will both learn about material science, bioengineering and biology, as well as the indispensable interaction between both fields. Scientific papers writing as well as conference attendance will be highly encouraged. International stays in other research centers are offered. Thus, a thorough formation in different skills (scientific writing, oral communication, IP protection, etc) will also be offered by the institution.
 PATENT: European Patent Application No. EP18382391.3 – CardioLoaf: eliciting cardiac tissue-like functionality at the macroscale (2018)
 Hortigüela V., Larrañaga E., Cutrale F., Seriola A., García-Díaz M., Lagunas A., Andilla J., Loza-Alvarez P., Samitier J., Ojosnegros S., Martinez E., Nanopatterns of surface-bound ephrinB1 produce multivalent ligand-receptor interactions that tune EphB2 receptor clustering. Nano Letters (2018); 18, (1), 629-637.
 Castaño AG; Hortigüela V, Lagunas A, Cortina C; Montserrat N; Samitier J; Martínez E. Protein patterning on hydrogels by direct microcontact printing: application to cardiac differentiation, RSC Adv. (2014); 4, 29120.