Nanofiber based artificial nerve graft for peripheral nerve regeneration

描述（由申请人提供）：周围神经损伤是一种常见病，每年影响数十万患者。严重的神经损伤导致在被切断的神经残端之间形成一个明显的间隙。当间隙较大（4mm）时，自体移植物通常用作“桥”。自体移植物并不理想，因为它们的可用性有限，并且患者暴露于第二次手术切口的发病率。到目前为止，已经研究了许多增强周围神经再生的方法。然而，没有一种方法比自体移植物手术更好，自体移植物是修复周围神经损伤的“黄金标准”。该建议的核心是开发基于纳米纤维的可生物降解神经移植物，在生物反应器中预先播种雪旺细胞，以增强周围神经再生，达到与自体移植物相当的水平。近年来，静电纺丝法制备高分子纳米纤维已被广泛应用于制造类似细胞外基质结构的纤维基质。纤维基质的高多孔三维结构可能对细胞附着、迁移、增殖、分化和基质蛋白沉积提供有益的控制。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。生物反应器培养系统有助于加快和促进人工神经移植物上雪旺细胞的生长。该研究项目将包括以下几个阶段：目标1：设计、制造和表征基于纳米纤维的可生物降解周围神经再生神经移植物；目的2：研究旋转生物反应器中纳米纤维基可降解神经移植物微环境下雪旺细胞的增殖情况；目的3：在体内评价含雪旺细胞神经移植物对周围神经间隙的桥接作用。公共卫生相关性：周围神经损伤是每年影响数十万患者的常见疾病。本研究将有助于周围神经损伤患者的治疗。

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.