Design of a novel class of biodegradable and functionalized polyesters for cardiac application – NANOCARDIOROP

This project is focused on the development of new methodologies to prepare aliphatic polyesters as precursors of new biodegradable nanoparticles and elastomers for cardiac applications. Cardiovascular diseases remain indeed the leading cause of death in the USA as an example, resulting in nearly US$ 300 billion in healthcare costs annually. The irreversible organ damage from myocardial infarction creates an urgent need for more potent biomaterials in cardiac therapy. Among the different treatments that have been developed, Vascular Endothelial Growth Factor (VEGF) and Insulin Growth Factors (IGFs) have demonstrated angiogenic and cardioprotective properties. It has been showed that the controlled delivery via polyester-based nanoparticles loaded with different growth factors could drastically enhance cardiac protection. The second main approach is based on the use of elastic, biodegradable cardiac patch based on 3D cross-linked polyesters to promote contractile muscle formation limiting the remodeling process and therefore improving the hemodynamic status.
However, whatever the approach, both types of biomaterials present some limitations that have to be overcome to significantly improve their performances and their practical use. The current techniques leading to functional aliphatic polyesters are indeed restricted to a limited number of monomers and/or require non-convenient multi-step synthesis processes. In addition, no facile functionalization strategies can be implemented in order to prepare traceable materials or covalent drug/polymer coupling to gather all the benefits of a prodrug (e.g., no burst release, controlled drug release, high drug loading, etc.).
The methodology we propose relies on the quasi-ideal radical copolymerization mechanism that occurs between cyclic ketene acetal monomers and vinyl derivatives, enabling the preparation of polyester backbone by a radical pathway in which functional groups can be readily and homogeneously inserted on the pending vinyl moieties through routine coupling pathways. Therefore, the method offers the advantage of using free radical chemistry (e.g., convenient experimental conditions, tolerance to functional groups, easy work-up…), low volume shrinkage and the possibility to prepare specific functional polyesters that are not possible by conventional methods.
This will lead to biodegradable materials with tunable features (e.g., degradation rate, functionalization). In particular we will prepare biodegradable nanoparticles and elastomers, both loaded with growth factors for further controlled release to the injured tissue.

Beyond the preparation of a new class of functionalized polyesters, the aim of this work is also to study the properties of such biomaterials (mechanical properties, degradation rate, in vitro cytotoxicity, etc) and finally to evaluate them through in vivo studies (rats) in on ischemic hearts.