Bio-inspired 3D scaffolds for cardiac tissue engineering – MimHeart

Context:
Tissue engineering is an approach allowing the replacement or repair of tissues or organs. The principle of this method mainly relies upon the promotion of cells growth on a bio-inspired scaffold that mimics the extra-cellular matrix (ECM) of the tissue which has to be repaired. The structure of organs is 3D, composite and hierarchically organized with characteristic length scales ranging from nm to mm.

Goals:
The main objective of the present project is to develop an original electrospinning/electrospraying process allowing the elaboration of the next generation of 3D biomimetic scaffolds for cardiac repair combining adjusted mechanical properties and a well-controlled hierarchical structure.

Methodology and expected results:
The project presents a strong multidisciplinary character. Thanks to the expertise and complementarity between the partners (ICPEES, IBPS-B2A), we propose the following work-packages to ensure the success of the project:
WP1 : Building 3D micro-patterned nanofibrous composite scaffolds
WP1 is dedicated to the control of the 3D structure and to the effect of this structure on the in vitro biological properties. An original process coupling the electrospinning and the electrospraying will be developed and the electrostatic interactions leading to the final microstructuration of the 3D scaffold will be explained and optimized with the help of numerical simulation. Different 3D structured scaffolds will be tested for optimization regarding myocardial regeneration. We will investigate the structural parameters of 3D functional scaffolds that allow the seeded cardiac cells to undergo terminal differentiation and a process of advanced organotypic assembly and maturation. This task will be considered successful if we obtain a scaffold leading to the development of a functional cardiac syncytium from seeded cardiac cells.

WP2 : 3D micro-patterned scaffolds with enhanced mechanical properties
WP2 is dedicated to the control of the mechanical properties of the scaffold. It has been recently shown that poly(glycerol sebacate) based elastomer (PGS) has a high potential for cardiac applications due to its biocompatibility/biodegradability and mechanical properties which can be tuned to those of the heart tissue. Thus, PGS prepolymers with different molar mass will be synthesized. They will then be processed by electrospraying and/or electrospinning with a template polymer such as poly(lactic acid) favoring the formation of the fibers. The crosslinking parameters of the PGS will then be optimized in order to tune the mechanical properties of the final materials. 3D PGS-based biomimetic scaffolds will finally be elaborated and tested by extensive in vitro and in vivo studies. This task will be considered successful if the grafted scaffold improves heart function and results in the formation of new functional cardiac tissue.

In conclusion, “MimHeart” project is at the same time highly innovative and pertinent for its scientific and technical aspects (i.e. coupling electrospinning and electrospraying processes for the elaboration of microstructured composites) as well as for its applications (i.e. biomaterials for cardiac engineering). The transverse approach of “MimHeart” allows the partners to perfectly integrate this project in their scientific strategies. Moreover, the whole investigated techniques will serve as a new platform for the development of novel kinds of microstructured nanofibrous composites for different application fields such as biomedical, sensors or catalytic materials. Finally, we believe that "MimHeart " project will ensure the establishment of a close and fruitful collaboration between the involved partners to develop innovative biomaterials for biomedical applications.