Magnetically Templated Regeneration Scaffolds for Nerve Injury Repair

用于神经损伤修复的磁模板再生支架

基本信息

批准号：
9086452
负责人：
Carlos M Rinaldi-Ramos
金额：
$ 21.91万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9086452
关键词：
Alginates Allografting Architecture Autologous Transplantation Axon Basal lamina Belief Biocompatible Biocompatible Materials Biodegradation Biological Biological Preservation Caliber Chemicals Cicatrix Clinic Clinical Collagen Cues Development Diffusion Encapsulated Engineering Ensure Excision Extracellular Matrix Figs - dietary Future Generations Goals Growth Health Hyaluronan Hydrogels In Vitro Inflammation Lead Length Magnetic nanoparticles Magnetism Methods Modeling Morbidity - disease rate Natural regeneration Nerve Nerve Regeneration Neurons Patients Pattern Peripheral Nerves Peripheral nerve injury Phase Pilot Projects Preparation Procedures Process Property Rattus Research Research Project Grants Research Proposals Risk Sampling Site Solvents Structure Technology Testing Toxic effect Translating Translations Tube Tubular formation Work aqueous axon growth base calginat clinically relevant cost crosslink design disease transmission experience immunogenicity implantable device in vitro testing in vivo injury and repair magnetic field nerve autograft nerve gap nerve injury nerve transection novel novel strategies prototype repaired research and development scaffold scale up sciatic nerve success technology development tissue repair

项目摘要

DESCRIPTION (provided by applicant): Despite significant efforts developing biomaterials to direct axon growth, decellularized nerve allografts and nerve autografts remain the only clinical alternatives for repairing peripheral nerve injuries with transected nerve gaps of 2-12 cm. It is our belief that this is because many biomaterials for nerve regeneration do not faithfully reproduce the tubular microstructure of natural nerve extracellular matrix. Specifically, success of decellularized nerve allografts in repairing nerve gaps of ~5 cm is in large part due to preservation of aligned ~10 µm diameter basal lamina tubes that direct axon growth and nerve reconnection. Unfortunately, nerve allografts require expensive processing procedures, limiting broad patient access due to high cost, and pose the risk of disease transmission. On the other hand, nerve autografts result in donor site morbidity and only 40- 50% success rates. Hence, there is a critical need for novel approaches to engineer regeneration scaffolds that may replace allografts and autografts in peripheral nerve injury repair. The goal of this exploratory/development project is to develop and test a new approach to obtain nerve regeneration scaffolds consisting of naturally derived crosslinked hydrogels with embedded tubular microstructure mimicking the nerve basal lamina. The proposed approach, magnetic templating, consists of dispersion of magnetic alginate microparticles in a pre-hydrogel solution, alignment of the microparticles into gap-spanning columnar structures with a magnetic field, hydrogel crosslinking in the field, and dissolution of the magnetic alginate microparticles, leavin behind aligned, continuous and interconnected gap-spanning channels with diameters that make them suitable for directing axon growth. Magnetic templating has the advantages of: (i.) aligned continuous tubular microstructure that mimics nerve basal lamina tubes in diameter and length; (ii.) compatibility with natural-based hydrogels, resulting in scaffolds with minimal immunogenicity or toxicity; (iii.) compatibility with biomolecules, enabling future incorporation o chemical and biological cues to further guide nerve growth; (iv.) scalability to lengths in centimeters; and (v.) process simplicity and scalability that will reduce cost and broaden patient base. We will achieve the project's goal through two specific aims designed to test our hypotheses: (AIM 1) that tubular structure alignment, diameter, and connectivity are determined by overall concentration, diameter and magnetic nanoparticle content of the magnetic alginate microparticles, and the magnitude and direction of the magnetic field applied during the templating process; and (AIM 2) that incorporation of linearly oriented channels through magnetic templating will increase axonal extension into hyaluronan/collagen hydrogels in vitro and in vivo. Completion of these studies will inform and motivate future phases of research to develop and translate magnetically templated regeneration scaffolds as alternatives for nerve allografts and autografts in peripheral nerve injury repair. This approach also has broad applicability for other tissue repair applications.

描述（由适用提供）：尽管为直接轴突生长开发了生物材料，但脱细胞神经移植和神经自体移植仍然是修复周围神经损伤的唯一临床替代方案，该神经损伤具有2-12 cm的跨性神经间隙。我们相信这是因为许多用于神经再生的生物材料不会忠实地重现天然神经细胞外基质的管状微观结构。具体而言，脱细胞神经合金在修复〜5 cm的神经间隙中的成功很大程度上是由于保留了直径〜10 µm直径的基本层层管，该层管直径为轴突生长和神经重新连接。不幸的是，神经合金需要昂贵的加工程序，从而限制了由于成本高而限制了患者的广泛通道，并构成了传播疾病的风险。另一方面，神经自体移植会导致供体部位发病率，仅40-50％的成功率。因此，对新方法进行了新的方法来设计新方法，以替代外周神经损伤修复中的同种异体移植和自体移植。该探索/开发项目的目的是开发和测试一种新的方法，以获得神经再生支架，这些脚手架由自然衍生的交联水凝胶和嵌入式管状微观结构组成，模仿神经基本的层。提出的方法，磁模板，包括磁性算法微粒的分散，将微粒子的对准与间隙跨度的柱状结构相反，并在磁场上进行水凝胶交联，在田间中交联，并散发出磁性算法的脱位，并置于磁性固定，并使其脱离，并置于隔离状态，互联网，互联网，互联网，gap是互联网的，gap gap gap gap gap gap。指导轴突生长。磁模板具有以下优点：（i。）对齐连续的管状微观结构，模仿神经基本的层状管的直径和长度；（ii。）与天然水凝胶的兼容性，导致脚手架具有最小的免疫原性或毒性；（iii。）与生物分子的兼容性，从而使未来的化学和生物学提示能够进一步指导神经生长；（iv。）可伸缩到长度为厘米的长度；（v。）流程简单性和可扩展性将降低成本并扩大患者基础。我们将通过旨在测试我们的假设的两个特定目的来实现项目的目标：（目标1）磁算法微粒的整体浓度，直径和磁性纳米粒子含量确定了管状结构对齐，直径和连通性，以及在模板过程中应用磁场的大小和方向的磁性算法和方向；（AIM 2）通过磁模板合并通道将在体外和体内增加轴突延伸到透明质酸/胶原水凝胶中。这些研究的完成将为并激发研究的未来阶段，以开发和翻译磁模板的再生支架，作为周围神经损伤修复中神经同种异体移植和自体移植的替代方法。该方法还具有针对其他组织修复应用的广泛可用性。