Nanofiber based artificial nerve graft for peripheral nerve regeneration

用于周围神经再生的纳米纤维人工神经移植物

• 批准号: 7740217
• 负责人: XIAOJUN YU
• 金额: $ 7.9万
• 依托单位: STEVENS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-15 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7740217
• 关键词: Adopted; Affect; Animal Model; Architecture; Area; Autologous Transplantation; Axon; Bioreactors; Cell Proliferation; Cell-Matrix Junction; Cells; Cues; Culture Media; Deposition; Development; Disease; Distal; Environment; Extracellular Matrix; Fiber; Fibrin; Gold; Growth; Hour; Injury; Liquid substance; Metabolic; Morbidity - disease rate; Natural regeneration; Nerve; Nerve Regeneration; Neurites; Nutrient; Organ; Patients; Peripheral Nerves; Peripheral nerve injury; Phase; Procedures; Process; Proteins; Rattus; Recovery; Recovery of Function; Research; Research Project Grants; Schwann Cells; Silicones; Staging; Structure; Supporting Cell; Surface; Surgical incisions; System; Time; Tissue Engineering; Tissues; Tube; Waste Products; axon regeneration; base; cell growth; cytotoxic; design; improved; in vivo; migration; nanofiber; nerve gap; nerve injury; neuron loss; neurotrophic factor; polycaprolactone; public health relevance; repaired; scaffold; sciatic nerve; success

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.

描述（由申请人提供）：周围神经损伤是每年影响数十万患者的常见疾病。 严重的神经损伤导致形成了切断的神经残端之间的显着差距。 当间隙较大（4毫米）时，自体移植通常用作“桥梁”。自体移植不是理想的，因为他们的可用性受到限制，并且患者暴露于第二个手术切口的发病率。 到目前为止，已经检查了许多方法以增强周围神经再生。 但是，它们都没有比自体移植手术更好，即修复周围神经损伤的“金标准”。 该提案的中心是生物反应器中用雪旺氏细胞播种的基于纳米纤维的可生物降解神经移植物的发展，以增强周围神经再生至与自体移植相当的水平。 通过静电纺丝制造聚合物纳米纤维，最近已用于形成纤维矩阵，这些基质可能紧密模仿细胞外基质（ECM）的结构。 纤维基质的高度多孔的三维（3D）结构可以对细胞附着，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对于神经再生的成功至关重要。 旋转的生物反应器是一种动态培养物的一种形式，旨在利用低剪切，三维性和高传质，以促进离体组织合成。 生物反应器培养系统将有助于固定和改善人造神经移植物上的schwann细胞生长。 研究项目将包括以下阶段：AIM 1：设计，捏造和表征基于纳米纤维的可生物降解神经移植物，用于周围神经再生； AIM 2：研究旋转生物反应器中基于纳米纤维的可生物降解神经移植的微环境中的Schwann细胞增殖； AIM 3：评估含有神经移植物的Schwann细胞，用于在体内动物模型中桥接周围神经间隙。 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。 拟议的研究将有助于帮助周围神经损伤的患者。