Design of 3D bioengineered cardiac tissue models for the evaluation of chemical cardiotoxicity

Humans are continuously exposed to a huge amount and a variety of chemicals. Animal tests are the gold standard for toxicity testing. However, they often fail in finely replicating the real physio-pathological scenario and their use is associated with ethical issues. 3D in vitro tissue models more efficiently mimic the native human environment and bring clear ethical advantages.¹ In order to design a 3D bioengineered tissue model, the 3D matrix used to guide cell behavior, extracellular matrix (ECM) production and new tissue formation should replicate the architecture and composition of the native tissue. In this context, the proper selection of the biomaterial, the fabrication method and the functionalization protocol plays a pivotal role. In cardiac tissue engineering (TE), elastomeric polymers are required as constituents of porous structs replicating in vitro the myocardium architecture and mechanical properties. Moreover, surface functionalization with cardiac ECM proteins replicates in vitro the biochemical cues present in the native tissue. In this work the versatility of poly(urethane) (PU) chemistry was exploited to design a plethora of polymers with a wide range of physico-chemical properties. The most promising material for cardiac TE was then microfabricated through melt extrusion additive manufacturing (AM). Scaffolds were surface functionalized with cardiac ECM proteins (e.g., laminin, LN) and seeded with cardiac progenitor cells (CPCs) to establish cardiac tissue models.