Long-Gap Nerve Regeneration by Pleiotrophic Support in Multiluminal Grafts

多腔移植物中多营养支持的长间隙神经再生

基本信息

批准号：
8306757
负责人：
Mario Ignacio Romero-Ortega
金额：
$ 18.18万
依托单位：
UNIVERSITY OF TEXAS ARLINGTON
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-01 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8306757
关键词：
Address Area Autologous Transplantation Axon Biocompatible Materials Biological Biomimetics Cell Proliferation Clinical Clinical Research Collagen Defect Distal Effectiveness Electron Microscopy Electrophysiology (science)Encapsulated Evaluation Extracellular Matrix FDA approved Failure Fibroblasts Filler Goals Growth Growth Factor Harvest Hydrogels Implant In Vitro Injury Label Mediating Methods Mitogens Modeling Morbidity - disease rate Motor NTF3 gene Natural regeneration Neonatal Nerve Nerve Growth Factors Nerve Regeneration Neural Conduction Neuroglia Neurons Neurotrophin 3 Oryctolagus cuniculus Peripheral Nerves Polyglycolic Acid Polymers Procedures Property Recovery of Function Relative (related person)Research Risk Schwann Cells Sensory Spinal Cord Testing Tissue Engineering Tissue Harvesting Tube Tubular formation Vascularization axon growth axon regeneration base behavior test biosynthetic material cell motility combinatorial controlled release design injured morphometry nerve gap nerve injury neurotrophic factor novel particle peroneal nerve pleiotrophin receptor regenerative repaired scaffold standard of care syndecan tissue repair

项目摘要

DESCRIPTION (provided by applicant): Several simple hollow tubes made of biosynthetic materials (i.e.,) polylactic-co-e-coprolactone, polyglycolide, collagen) are currently FDA-approved and have demonstrated clinical benefit in the repair of short nerve gaps. However, autografts remain the treatment of choice for nerve defects despite the need of donor nerve harvest and the associated morbidity of this procedure. In contrast to short gap injuries, autografts achieve minimal functional recovery for nerve defects longer than 30 mm and simple tubularization methods fail completely in repairing this critical gap. The regenerative failure of peripheral nerves through long-gaps seems to be due at least in part, to the lack of appropriate growth substrate and trophic support. We hypothesize that a growth factor strategy targeted to a broad cellular base in the regenerating nerves would be highly effective in achieving simultaneous cellularization, vascularization and nerve regeneration through long nerve gaps. A systematic evaluation of the trophic support needed for long-gap nerve repair, as well as the combination of increased regenerative area and pleiotrophic growth factor support is lacking. This study will address this need. In our preliminary studies, we have demonstrated that multiluminal nerve repair and pleiotrophic growth factors can successfully mediate nerve regeneration across a 30 mm gap. The overall goal of the proposed study will be focused on extending these results and systematically test the effect of neurotrophic factors (i.e., NGF and NT-3) alone or combined with PTN in long gap nerve repair. In Specific Aim 1 we will test the regenerative potency of combined Neurotrophin-Pleiotrophin treatment in vitro. In Specific Aim 2 we will evaluate the effect of neurotrophin/pleiotrophic growth factor support over long-gap nerve regeneration of the rabbit common personal nerve. This study is novel in that: 1) utilizes multicellular growth factors to stimulate both glial cellular proliferation and migration, and axonal regeneration, 2) uses collagen-suspended polymeric microparticles with encapsulated growth factors for controlled release, and 3) utilizes a recently developed multiluminal hydrogel nerve scaffold as biomimetic structural support. This research will contribute towards the elucidation of the structural and trophic support required to repair long gap nerve injuries trough biosynthetic nerve implants.

描述（由申请人提供）：几种由生物合成材料（即聚乳酸-co-e-coprolactone、聚乙交酯、胶原蛋白）制成的简单空心管目前已获得 FDA 批准，并已证明在修复短神经间隙方面具有临床益处。然而，尽管需要采集供体神经并且该手术存在相关的发病率，但自体移植仍然是神经缺陷的治疗选择。与短间隙损伤相比，自体移植物对于长度超过 30 毫米的神经缺损只能实现最小的功能恢复，而简单的管状化方法完全无法修复这一关键间隙。周围神经通过长间隙的再生失败似乎至少部分是由于缺乏适当的生长基质和营养支持。我们假设，针对再生神经中广泛细胞基础的生长因子策略将非常有效地通过长神经间隙同时实现细胞化、血管化和神经再生。缺乏对长间隙神经修复所需的营养支持以及增加再生面积和多效生长因子支持的组合的系统评估。本研究将解决这一需求。在我们的初步研究中，我们已经证明多腔神经修复和多效生长因子可以成功介导跨 30 毫米间隙的神经再生。拟议研究的总体目标将集中于扩展这些结果并系统地测试神经营养因子（即 NGF 和 NT-3）单独或与 PTN 联合在长间隙神经修复中的效果。在具体目标 1 中，我们将在体外测试神经营养蛋白-多效营养蛋白联合治疗的再生效力。在具体目标 2 中，我们将评估神经营养蛋白/多效生长因子支持对兔子常见神经长间隙神经再生的影响。这项研究的新颖之处在于：1）利用多细胞生长因子刺激神经胶质细胞增殖和迁移以及轴突再生，2）使用含有封装生长因子的胶原悬浮聚合物微粒进行控制释放，3）利用最近开发的多腔水凝胶神经支架作为仿生结构支撑。这项研究将有助于阐明通过生物合成神经植入物修复长间隙神经损伤所需的结构和营养支持。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Coiled polymeric growth factor gradients for multi-luminal neural chemotaxis.

用于多腔神经趋化性的卷曲聚合物生长因子梯度。

DOI：
发表时间：
2015-09-04
期刊：
影响因子：
2.9
作者：
Alsmadi, Nesreen Zoghoul;Patil, Lokesh S;Hor, Elijah M;Lofti, Parisa;Razal, Joselito M;Chuong, Cheng;Wallace, Gordon G;Romero
通讯作者：
Romero

Glial-derived growth factor and pleiotrophin synergistically promote axonal regeneration in critical nerve injuries.

胶质源性生长因子和多效蛋白协同促进严重神经损伤的轴突再生。

DOI：
发表时间：
2018
期刊：
影响因子：
9.7
作者：
Alsmadi, Nesreen Zoghoul;Bendale, Geetanjali S;Kanneganti, Aswini;Shihabeddin, Tarik;Nguyen, An H;Hor, Elijah;Dash, Swarup;Johnston, Benjamin;Granja;Romero
通讯作者：
Romero

Pleiotrophin-Neuregulin1 promote axon regeneration and sorting in conduit repair of critical nerve gap injuries.

多效蛋白-神经调节蛋白1在严重神经间隙损伤的导管修复中促进轴突再生和分选。