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（由申请人提供）：尽管在开发生物材料来引导轴突生长方面做出了巨大努力，但脱细胞同种异体神经移植物和自体神经移植物仍然是修复2-12厘米横切神经间隙的周围神经损伤的唯一临床替代方案。因为许多用于神经再生的生物材料不能忠实地再现天然神经细胞外基质的管状微观结构，具体而言，脱细胞神经同种异体移植物在修复神经间隙方面取得了成功。 ~5 cm 很大程度上是由于保留了对齐的 ~10 µm 基底直径的椎板管，这些椎板管引导轴突生长和神经重新连接。不幸的是，神经同种异体移植需要昂贵的处理程序，由于成本高而限制了广泛的患者接触，并带来了风险。另一方面，自体神经移植会导致供体部位发病，并且成功率仅为 40-50%，因此，迫切需要设计可替代的再生支架的新方法。该探索/开发项目的目标是开发和测试一种新方法，以获得由天然衍生的交联水凝胶组成的神经再生支架，该水凝胶具有模仿神经基底层的嵌入管状微结构。磁性模板，包括将磁性藻酸盐微粒分散在预水凝胶溶液中，利用磁性将微粒排列成跨间隙的柱状结构。磁场中的水凝胶交联以及磁性藻酸盐微粒的溶解，留下对齐的、连续的和互连的间隙跨越通道，其直径使其适合引导轴突生长，具有以下优点：（i.）对齐。连续管状微结构在直径和长度上模仿神经基底层管；（ii）与天然水凝胶相容，从而产生具有最小免疫原性或毒性的支架； (iii.) 与生物分子的兼容性，使未来能够结合化学和生物线索来进一步指导神经生长；(iv.) 可扩展至厘米长度；以及 (v.) 工艺简单性和可扩展性，这将降低成本并扩大患者基础。我们将通过两个旨在测试我们假设的具体目标来实现该项目的目标：（目标 1）管状结构排列、直径和连接性由磁性藻酸盐的总体浓度、直径和磁性纳米颗粒含量决定微粒，以及在模板化过程中施加的磁场的大小和方向；以及（目标 2）通过磁性模板合并线性定向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。将为未来阶段的研究提供信息和激励，以开发和转化磁模板再生支架作为周围神经损伤修复中同种异体神经移植物和自体移植物的替代品。广泛适用于其他组织修复应用。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Preparation and evaluation of microfluidic magnetic alginate microparticles for magnetically templated hydrogels.

用于磁性模板水凝胶的微流控磁性海藻酸盐微粒的制备和评价。

DOI：
10.1016/j.jcis.2019.11.040
发表时间：
2019-11-13
期刊：
Journal of colloid and interface science
影响因子：
9.9
作者：
Ishita Singh;Christopher S Lacko;Zhiyuan Zhao;C. Schmidt;C. Rinaldi
通讯作者：
C. Rinaldi

Magnetic particle templating of hydrogels: engineering naturally derived hydrogel scaffolds with 3D aligned microarchitecture for nerve repair.

水凝胶的磁粒子模板：利用 3D 对齐微结构设计天然水凝胶支架，用于神经修复。

DOI：
发表时间：
2020
期刊：
影响因子：
0
作者：
Lacko, Christopher S;Singh, Ishita;Wall, Monica A;Garcia, Andrew R;Porvasnik, Stacy L;Rinaldi, Carlos;Schmidt, Christine E
通讯作者：
Schmidt, Christine E

Development of a magnetically aligned regenerative tissue-engineered electronic nerve interface for peripheral nerve applications.

开发用于周围神经应用的磁对准再生组织工程电子神经接口。

DOI：
10.1016/j.biomaterials.2021.121212
发表时间：
2021-12
期刊：
Biomaterials
影响因子：
14
作者：
M. Kasper;Bret Ellenbogen;Ryan Hardy;Madison Cydis;Jorge A Mojica;Abdullah Afridi;Benjamin S. Spearman;Ishita Singh;Cary A. Kuliasha;Eric W. Atkinson;K. Otto;J. Judy;Carlos M. Rinaldi‐Ramos;C. Schmidt
通讯作者：
C. Schmidt

Processing-Size Correlations in the Preparation of Magnetic Alginate Microspheres Through Emulsification and Ionic Crosslinking.

通过乳化和离子交联制备磁性海藻酸盐微球的加工尺寸相关性。