Advanced tissue engineering systems to promote the functionality of cells derived from the peripheral nervous system in synthetic nerve conduits

先进的组织工程系统可促进合成神经导管中周围神经系统细胞的功能

• 批准号: RGPIN-2019-06055
• 负责人: Lauzon, MarcAntoine
• 金额: $ 2.04万
• 依托单位: Université de Sherbrooke
• 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=715916
• 关键词: Advanced; tissue; engineering; systems; promote

Severe peripheral nerve injuries (PNI) following traumas affect many people of the active population, thus creating a huge social-economical burden. The current gold standard for the repair of PNI with large gaps remains autograft, while short gap injuries can be treated with synthetic nerve conduits (SNCs). However, such SNCs generally lead to poor cell colonization, alignment and growth, which results in dysfunctional tissue regeneration and recovery. As an alternative, tissue engineering strategies are being developed to promote cell growth and guidance. Novel tissue engineering approaches now involve more advanced biomaterials with controlled structure and neurotrophic factors pre-seeded with glial or mesenchymal stem cells. However, those systems are usually restrained to static culture conditions, which limits the survival and growth rate of cells, and so the size of the SNCs. One approach to overcome those limitations would require the combination of such biomaterials with a dynamic culture system. Nonetheless, the impact of dynamic culture conditions on glial and neuronal cells and underlying behaviors using engineered scaffolds remains poorly understood. The proposed research program aims to study the effect of dynamic culture conditions on glial cells, stem cells and neuronal cells behavior seeded on composite SNCs having oriented micro-channels and embedded growth factors. The combination of a dynamic culture system, acute engineered biomaterials, and potent growth factors will provide a more accurate in vitro environment to study and optimize innovative tissue engineering strategies in the context of the peripheral nervous system. The proposed research program will enable the training of highly qualified personnel, who will benefit from a stimulating and interdisciplinary working environment. Throughout their formation, they will acquire a sought-after expertise by developing both fundamental (biochemistry) and applied knowledge (tissue engineering, applied neuroscience). This particular knowledge will give crucial insights for the development of a new generation of cell-biomaterial constructs that can be used in the future to facilitate or enhance current nerve regeneration treatments. It will contribute to reinforce the position of Canada in the domain of 3D culture systems and biomaterials.

创伤后严重的周围神经损伤（PNI）影响了许多活跃人群，从而造成了巨大的社会经济负担。目前修复大间隙PNI的金标准仍然是自体移植，而短间隙损伤可以用合成神经导管（SNCs）治疗。然而，此类SNCs通常会导致细胞定植、排列和生长不良，从而导致组织再生和恢复功能失调。作为替代方案，正在开发组织工程策略以促进细胞生长和引导。 新的组织工程方法现在涉及更先进的生物材料与控制的结构和神经营养因子预接种神经胶质或间充质干细胞。然而，这些系统通常限于静态培养条件，这限制了细胞的存活和生长速率，因此限制了SNC的大小。克服这些限制的一种方法将需要将这种生物材料与动态培养系统相结合。然而，动态培养条件对神经胶质细胞和神经元细胞的影响以及使用工程支架的潜在行为仍然知之甚少。 拟议的研究计划旨在研究动态培养条件对神经胶质细胞、干细胞和神经元细胞行为的影响，这些细胞接种在具有定向微通道和嵌入生长因子的复合SNCs上。动态培养系统、急性工程化生物材料和强效生长因子的组合将提供更准确的体外环境，以研究和优化外周神经系统背景下的创新组织工程策略。 拟议的研究计划将使高素质的人才，谁将受益于一个刺激和跨学科的工作环境的培训。在整个形成过程中，他们将通过发展基础知识（生物化学）和应用知识（组织工程，应用神经科学）获得抢手的专业知识。这一特殊的知识将为开发新一代细胞生物材料结构提供重要的见解，这些结构可在未来用于促进或增强当前的神经再生治疗。这将有助于加强加拿大在3D培养系统和生物材料领域的地位。