Cardiac tissue engineering aims to generate in vivo-like functional tissue for the study of cardiac development, homeostasis, regeneration and disease. Since the heart is composed of various types of cells and extracellular matrix with a specific microenvironment, the fabrication of cardiac tissue in vitro requires integrating technologies of cardiac cells, biomaterials, fabrication to model the complexity of heart tissue. In the current study we aim to evaluate gelatin-based cryogels for the generation of hybrid cellular cardiac tissue. Specifically, we would like to generate a cardiac model of cardiomyocytes and cardiac stromal cell niche, named cardiospheres (CSps). CSps contain a core of primitive, proliferating cells, and an outer layer of mesenchymal/stromal cells and differentiating cells that express cardiomyocyte-specific proteins and are characterized by high paracrine activity and tissue remodeling properties which should help CM maturation and functionality. Moreover, the hybrid scaffold could represent a valid model to study stromal cell population and myofibroblast activation and proliferation following myocardial infarction and could represent a powerful tool to evaluate the remodeling process as well as for the screening of new drugs.
This project has a strong interdisciplinary approach bringing together experts in the field of tissue engineering, cellular biology, biomaterials and chemical engineering for the study and evaluation of new types of biomaterials as well as for the generation of new tissue models for in vitro or in vivo applications.
Cardiac tissue engineering aims at creating contractile structures that can optimally reproduce the features of human cardiac tissue. These constructs are becoming valuable tools to model some of the cardiac functions, to set preclinical platforms for drug testing, or to alternatively be used as therapies for cardiac repair approaches. Most of the recent developments in cardiac tissue engineering have been made possible by important advances regarding the efficient generation of cardiac cells from pluripotent stem cells and the use of novel biomaterials and microfabrication methods. In healthy tissue, stromal cardiac cells are activated following pathological stimuli, and the in the case of myocardial infarction, are responsible for tissue remodeling which ultimately lead to fibrotic tissue deposition. In the current available models, fibroblasts are combined with cardiomyocytes to increase tissue strength and allow a better maturation of the cultured myocytes. Fibroblast proliferation, although beneficial to increase the mechanical properties of the tissue, ultimately leads to an altered cardiomycytes / fibroblast ratio that fail to recapitulate the healthy tissue microenvironment. In our current approach we want to use cardiac stromal cell spheroids, named cardiospheres, in combination with CM to recreate a cardiac tissue model with stromal cell niche which would be a better tool in studying stromal cell activation following pathological stimuli which should potentially better recapitulate the in vivo pathological tissue response. Moreover, it has been shown that cardiospheres secret a vast variety of growth factor with anti-apoptic, pro- proliferative effects, together with a better capability of extracellular matrix secretion and tissue formation thereby being potentially a better substitute of the fibroblast in the generation and maturation of cardiac constructs. Our model can be then further used for drug screening, disease modelling and eventually even for in vivo application and may overcome the observed limitation in the use of fibroblast for the generation of cardiac tissue.
Moreover, we are also investigating the used of these newly generated cryogels by the Sapienza teams which could then be used for a variety of tissue engineering applications and increase the biomaterials available in the tissue engineering field.