Modular injectable scaffolds for cell therapy and 3D bioprinting

点击翻译按钮获取中文摘要

The present research program aims to develop biomaterials scaffolds as engineering tools to improve the efficacy of cell therapy. Cell therapy consists in the transplantation of cells into patients and can be used to treat many diseases or repair tissues. However injected cells dye rapidly or are flushed from the tissue. Cell encapsulation in hydrogel scaffolds has the potential to improve cell therapy outcomes by enhancing cell viability and retention at the delivery site, but ideal scaffold are still missing. Moreover, the scaffold parameters that influence the survival and ability of cells to migrate towards the targeted tissue are still poorly understood. In the recent years, the candidate has been developing biodegradable in situ gelling hydrogels with enhanced mechanical properties and excellent cytocompatibility. Cells can be mixed to the pre-hydrogel solution when still liquid at room temperature and injected by needle or catheter. A cohesive gel rapidly form in vivo. The present project aims to further improve these injectable cell carriers, namely by improving cell microenvironment, facilitating oxygen diffusion to the cells and increasing their adhesion to the target tissues. The main approaches will consist in 1) the incorporation of extracellular matrix compounds into hydrogels to better reproduce normal cell-tissue interactions 2) the development of void-forming (macroporous) scaffolds using rapidly biodegradable microspheres, and 3) the fabrication of cell-carriers in the form of microspheres that can self-assemble in vivo. We hypothesize that compared to encapsulation in large hydrogel volumes, encapsulation in microspheres will improve oxygen diffusion to the cells, facilitate cell escape and eventually promote formation of blood vessel network that will provide oxygen and nutrients to the cells. We will also optimize the microencapsulation process to allow endothelial cells adhesion on the surface and thus accelerate the formation of a perfusable vascular network. In addition, we will optimize these injectable hydrogels as bioinks for 3D bioprinting. This additive manufacturing process allows to form tissue-like structures with controlled heterogeneity and personalized geometry, which can be used as 3D in vitro models, or as implantable scaffolds. However only a few bioinks are available and most of them are based on the non-biodegradable alginate. In this project, we will propose new bioinks based on chitosan- methacrylated gelatin interpenetrating networks. These new injectable modular cell carriers will offer many opportunities as tools for cell therapy and formation of 3D models and will bring significant knowledge on the factors influencing the success of cell carrier for cell therapy. A final benefit is the training of high-quality, highly qualified personnel (HQP) in this important field at the frontier between biomaterials science, rheology, mechanical engineering and biology.