ARC Centre for Electromaterials Science and Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, NSW 2519, Australia.
J Neural Eng. 2013 Feb;10(1):016008. doi: 10.1088/1741-2560/10/1/016008. Epub 2013 Jan 3.
Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate hydrogel. This indicates return of some feeling to the limb via the fully-configured conduit. Immunohistochemical analysis of the implanted conduits removed from the rats after the four-week implantation period confirmed the presence of myelinated axons within the conduit and distal to the site of implantation, further supporting that the conduit promoted nerve repair over this period of time. This study describes the design considerations and fabrication of a novel multicomponent, multimodal bio-engineered synthetic conduit for peripheral nerve repair.
外周神经系统（PNS）中的神经组织损伤会导致肢体功能长期受损、感觉异常和疼痛，通常还伴有心理影响。虽然较小的损伤可以在不干预的情况下自行再生，并且 2cm 以内的小间隙可以缝合，但较大或更严重的损伤通常需要从身体其他部位采集自体神经移植物（通常是感觉神经）。功能恢复通常并不理想，并且与所采集神经支配的组织感觉丧失有关。神经修复中持续存在的挑战导致了使用非神经生物组织和各种聚合物的神经引导物或导管的发展，以改善 PNS 中受损神经修复的预后。本研究描述了一种使用聚乳酸（PLA）和（PLA）：聚（乳酸-共-羟基乙酸）（PLGA）纤维在富含神经营养因子的藻酸盐水凝胶内制造多模式可控孔径神经再生导管的设计和制造。神经修复导管设计包括两种特定用于促进轴突生长和雪旺细胞生长的 PLGA 纤维（用于轴突的 75:25；用于雪旺细胞的 85:15）。这些排列的纤维包含在涂有电纺 PLA 纳米纤维以控制孔径的编织 PLA 护套的管腔中。神经修复导管管腔中的 PLGA 引导纤维由富含神经营养因子（NT-3 或 BDNF 与 LIF、SMDF 和 MGF-1）的藻酸盐水凝胶支撑，以提供神经保护、刺激轴突生长和雪旺细胞迁移。该导管用于在 4 周的时间内促进大鼠坐骨神经横断的修复。在此期间，观察到与仅植入藻酸盐水凝胶的导管的大鼠相比，植入全构型导管的大鼠的肢体过度梳理和自残（自截）明显减少。这表明通过全构型导管恢复了一些肢体感觉。从大鼠体内取出植入 4 周后的植入导管进行免疫组织化学分析，确认了在导管内和植入部位远端存在有髓轴突，进一步支持在这段时间内导管促进了神经修复。本研究描述了一种新型多成分、多模式生物工程合成外周神经修复导管的设计考虑因素和制造方法。
