Tuning hierarchical architecture of 3D polymeric scaffolds for cardiac tissue engineering

Tissue engineering combines the fields of engineering, chemistry, biology, and medicine to fabricate replacement tissues able to restore, maintain, or improve structurally and functionally damaged organs. The approach of regenerative medicine is of paramount importance for treating patients with severe cardiac diseases. For successful exploitation, the challenge for cardiac regenerative medicine is to identify the suitable combination between the best cell source for cardiac repair and the design of the optimal scaffold as a template for tissue replacement. Adult stem cells have the potential to improve regenerative medicine with their peculiar feature to self-renew and differentiate into various phenotypes. Insights into the stem cell field lead to the identification of the suitable scaffold features that enhance the ex vivo proliferation and differentiation of stem cells. Scaffolds composed of natural and/or synthetic polymers can organise stem cells into complex architectures that mimic native tissues. To achieve this, a proper design of the chemical, mechanical, and morphological characteristics of the scaffold at different length scales is needed to reproduce the tissue complexity at the cell-scaffold interface. Hierarchical porosities are needed in a single construct, at the millimetre scale to help nutrition and vascularisation, at the micrometer scale to accommodate cells, and at the nanometre scale to favour the expression of extra-cellular matrix components. The present study has been undertaken to setup strategies to integrate stem cells and tailored scaffolds, as a tool to control cardiac tissue regeneration. Among the many available techniques for scaffold fabrication, porogen leaching, phase separation, and electrospinning were selected as low-cost and user-friendly technologies to fabricate tuneable, hierarchically porous matrices that mimic aspects of the cell native surroundings. The biological validation of these scaffolds was performed by implanting adult stem cells.