Injectable thermosensitive hydrogels with enhanced mechanical properties for cell therapy

用于细胞治疗的具有增强机械性能的可注射热敏水凝胶

• 批准号: RGPIN-2015-05169
• 负责人: Lerouge, Sophie
• 金额: $ 2.55万
• 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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=613393
• 关键词: Injectable; thermosensitive; hydrogels; enhanced; mechanical

Injectable hydrogels are increasingly used for minimally invasive treatment of diseases, especially in combination with cell seeding, because they can ensure appropriate cell localization, retention and survival. Ideally, an injectable gel should have relatively low viscosity before and during injection but gel rapidly and exhibit high mechanical strength after being delivered, to ensure matrix cohesion and tolerance to in vivo stresses. However, there is a lack of injectable material that combines these qualities with excellent cell compatibility. Our team recently developed a method for preparing high-strength, fast-thermogelling chitosan (CH)-based hydrogels using new gelation agents that may solve this issue. The objectives of this 5-year research program are to design, optimize and characterize these thermosensitive hydrogels for use as injectable scaffolds, especially in cell therapy, and to explore their potential for additive manufacturing of tissue using 3D bioprinting. We will first study how the gelation kinetic, mechanical properties and porosity are influenced by gel composition, to better understand why CH gels containing sodium hydrogen carbonate (SHC) present much higher mechanical properties and to be able to tailor a gel’s properties as needed for a specific application. We will then evaluate their suitability for encapsulation of human mesenchymal stem cells (MSCs) and T lymphocytes, both of which hold great promise in cell therapy. MSC survival and therapeutic efficiency will be optimized by two different approaches: a) pharmacological preconditioning of cells before encapsulation and b) design of bioactive scaffolds containing chondroitin sulfate and growth factors. Finally we will leverage these customizable hydrogels for use in bioprinting, which makes it possible to create complex and heterogeneous 3D structures mimicking living tissues, with potential applications for tissue engineering, drug screening and toxicology. A dozen students will be involved in this research program, including 2 PhDs, 3 Masters and 2 post-doctoral students. While we do not target any specific clinical application for this grant, our work will contribute knowledge and data toward the development of minimally invasive treatments with increased efficacy and reduced risk (thanks to more local delivery), thereby reducing costs and morbidity rates. Thus, in the long term, benefits for Canadian health and industry are also expected from our research results and the training of high-quality HQP in this strategic field.

可注射水凝胶越来越多地用于疾病的微创治疗，特别是与细胞接种相结合，因为它们可以确保适当的细胞定位、保留和存活。理想情况下，可注射凝胶在注射前和注射期间应具有相对较低的粘度，但能快速凝胶并表现出。交付后具有较高的机械强度，以确保基质内聚力和对体内应力的耐受性。然而，我们的团队最近开发了一种将这些品质与出色的细胞相容性结合在一起的可注射材料。使用新型胶凝剂的高强度、快速热胶凝壳聚糖（CH）基水凝胶可以解决这个问题。 这个为期 5 年的研究计划的目标是设计、优化和表征这些热敏水凝胶，用作可注射支架，特别是在细胞治疗中，并探索它们使用 3D 生物打印增材制造组织的潜力。 我们将首先研究凝胶成分如何影响凝胶动力学、机械性能和孔隙率，以便更好地理解为什么含有碳酸氢钠 (SHC) 的 CH 凝胶具有更高的机械性能，并能够根据需要定制凝胶的性能。然后，我们将评估它们封装人类间充质干细胞 (MSC) 和 T 淋巴细胞的适用性，这两种细胞在细胞治疗中都具有巨大的前景，并且将通过两种不同的方法来优化 MSC 的存活和治疗效率：封装前对细胞进行药理学预处理，b) 设计含有硫酸软骨素和生长因子的生物活性支架。最后，我们将利用这些可定制的水凝胶用于生物打印，这使得创建模仿活体组织的复杂且异质的 3D 结构成为可能，具有潜在的应用。用于组织工程、药物筛选和毒理学。 十多名学生将参与该研究项目，其中包括 2 名博士生、3 名硕士生和 2 名博士后生。虽然我们的资助不针对任何特定的临床应用，但我们的工作将为微创的发展贡献知识和数据。因此，从长远来看，我们的研究成果和高质量 HQP 的培训也有望为加拿大的健康和工业带来好处。在这个战略领域。