Nanofiber based artificial nerve graft for peripheral nerve regeneration

描述(申请人提供)：周围神经损伤是一种常见疾病，每年影响数十万患者。严重的神经损伤导致切断的神经残端之间形成明显的缝隙。当间隙较大时(4毫米)，通常使用自体骨作为“桥梁”。自体移植并不理想，因为它们的可用性有限，而且患者暴露在第二次手术切开的并发症中。到目前为止，已经研究了许多促进周围神经再生的方法。然而，它们中没有一个比自体移植手术表现得更好，自体移植手术是修复周围神经损伤的“黄金标准”。这项建议的核心是开发基于纳米纤维的生物可降解神经移植物，在生物反应器中预先种植雪旺细胞，以促进周围神经再生，达到与自体移植相当的水平。最近，通过静电纺丝制备的聚合物纳米纤维被用来形成与细胞外基质(ECM)结构非常相似的纤维基质。纤维基质的高度多孔的三维(3D)结构可以提供对细胞附着、迁移、增殖、分化和基质蛋白沉积的有益控制。雪旺细胞在基质上的附着和迁移是神经再生成功的关键。旋转生物反应器是一种动态培养形式，旨在利用低剪切、三维和高传质来促进体外组织合成。该生物反应器培养系统将有助于雪旺细胞在人工神经移植物上的生长。本研究项目将包括以下几个阶段：目的1：设计、制备和表征用于周围神经再生的纳米纤维可生物降解神经移植物；目的2：在旋转生物反应器中研究基于纳米纤维的可生物降解神经移植物微环境中许旺细胞的增殖情况；目的3：在体内动物模型中评价含雪旺细胞的神经移植物修复周围神经缺损区的作用。与公共卫生相关：周围神经损伤是一种常见疾病，每年影响数十万患者。建议的研究将有助于帮助周围神经损伤的患者。

DESCRIPTION (provided by applicant): Peripheral nerve injuries are common diseases that affect hundreds of thousands of patients every year. Severe nerve injuries result in the formation of a significant gap between the severed nerve stumps. When the gap is large (4 mm), autografts are commonly used as "bridges." Autograft is not ideal because their availability is limited and the patient is exposed to the morbidity of a second surgical incision. Up to the present, many approaches have been examined for enhancing peripheral nerve regeneration. However, none of them has performed better than autograft procedures, the 'gold standard' for repairing peripheral nerve injuries. At the center of this proposal is the development of nanofiber based biodegradable nerve grafts pre- seeded with Schwann cells in bioreactors for enhancing peripheral nerve regeneration to the level comparable to autograft. The fabrication of polymeric nanofibers by electrospinning has recently been used to form fibrous matrices that may closely mimic the structure of the extracellular matrix (ECM). The highly porous three- dimensional (3D) architecture of the fibrous matrix may provide beneficial control of cell attachment, migration, proliferation, differentiation, and matrix protein deposition. The attachment and migration of Schwann cells on the matrix are critical for the success of nerve regeneration. The rotating bioreactor is a form of dynamic culture designed to utilize low shear, three-dimensionality, and high mass transfer to promote ex vivo tissue synthesis. The bioreactor culture system will be helpful to fasten and improve Schwann cell growth on the artificial nerve graft. The research project will include the following phases: Aim 1: Design, fabricate and characterize a nanofiber based biodegradable nerve graft for peripheral nerve regeneration; Aim 2: Investigate Schwann cell proliferation in the microenvironment of nanofiber based biodegradable nerve graft in rotating bioreactors; Aim 3: Evaluate the Schwann cell containing nerve graft for bridging peripheral nerve gaps in an animal model in vivo. PUBLIC HEALTH RELEVANCE: Peripheral nerve injuries are common diseases that affect hundreds of thousands of patients every year. The proposed research will be helpful to aid patients with peripheral nerve injuries.