Modular injectable scaffolds for cell therapy and 3D bioprinting

用于细胞治疗和 3D 生物打印的模块化可注射支架

• 批准号: RGPIN-2020-06684
• 负责人: Lerouge, Sophie
• 金额: $ 4.01万
• 依托单位: École de technologie supérieure
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=717761
• 关键词: Modular; injectable; scaffolds; cell; therapy

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.

目前的研究项目旨在开发生物材料支架作为工程工具，以提高细胞治疗的疗效。细胞疗法包括将细胞移植到病人体内，可用于治疗许多疾病或修复组织。然而，注射的细胞迅速染色或从组织中冲洗出来。水凝胶支架中的细胞包封有可能通过增强细胞活力和在递送部位的保留来改善细胞治疗结果，但理想的支架仍然缺乏。此外，影响细胞向目标组织迁移的存活和能力的支架参数仍然知之甚少。