Biomateriales 2

Summary

This project proposes an investigation for the modulation of pancreatic tumors through a strategic performance of low intensity ultrasound as a new technological approach for cancer research. A study will be carried out of the mechanical properties and stresses developed inside tumors, as well as of the biodynamic interactions in the tumor microenvironment, and the response in genes and other biomarkers, intrinsically related to the evolution of the tumor, will be analyzed. The project involves researchers from different disciplines: biologists, chemists, oncologists, medical experts in pathological anatomy, physicists and engineers. Tumors of the digestive tract are one of the most common types of cancer. Pancreatic adenocarcinoma (PDAC) is the 4th leading cause of cancer death, with a mortality rate almost equal to the incidence rate. This disease is highly resistant to treatment due in many cases to the desmoplastic stroma that acts as a barrier to the entry of drugs and immune cells, thus limiting the use of chemotherapy. Mechanopathology has recently been identified as a marker of cancer biology. Tumors exert solid stresses arising from the solid components of the tumor microenvironment, including cells and the extracellular matrix. These stresses promote tumor growth and compress the lymphatic vessels, inducing hypoxia. Thus the effectiveness of the therapies is inhibited. Recent studies of the literature present models of the tumor microenvironment to study how physics affects tumors and revealed that cell movements are governed by mechanical forces of interaction between cells and between cells and the extracellular matrix. The adhesion capacity of cancer cells to the stroma that surrounds them induces intracellular contraction forces that deform their microenvironment through the alignment of collagen fibers, altering its mechanical properties. Thus, we intend in this Project to study the effects of intercellular and cell-ECM interactions through a new technological strategy based on the use of low intensity ultrasound combining bioprinted models, 2D and 3D cell samples, as well as ex-vivo and in vivo samples of mouse. The key advantage of 3D printing cancer cells is the potential to model the tumor microenvironment in-vitro with very high fidelity, offering a greater representation of tumor formation and progress to analyze its response to drugs and avoiding the use of animal samples. . The project also aims to study the elastic properties in macro samples of anisotropic tissues to determine internal stresses and to build a special map of their elastic properties. The study of Young's modulus as a tensor in highly anisotropic tumors is of special interest to understand the progression of their malignancy.