Development of Poly (pro-curcumin) Polymer Coatings to Improve Cortical Electrode Biocompatibility

开发聚（姜黄素原）聚合物涂层以改善皮质电极生物相容性

• 批准号: 10352198
• 负责人: Ryan J. Gilbert
• 金额: --
• 依托单位: STRATTON VETERANS ADMIN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10352198
• 关键词: Animals; Anti-Inflammatory Agents; Astrocytes; Attenuated; Biocompatible Materials; Biodegradation; Biomaterials Research; Brain; Characteristics; Chemistry; Cicatrix; Collaborations; Curcumin; Data; Development; Devices; Disease; Dose; Drug Delivery Systems; Electrodes; Estrogens; Event; Failure; Fiber; Film; Free Radicals; Hour; Implant; Individual; Inflammation; Inflammatory; Inflammatory Response; Injury; Interdisciplinary Study; Kinetics; Lead; Lesion; Libraries; Longevity; Measures; Mechanics; Microelectrodes; Modeling; Molecular Weight; Nature; Nerve Degeneration; Neuraxis; Neurons; Neurosciences Research; Outcome; Oxidants; Paralysed; Pharmaceutical Preparations; Pilot Projects; Plant Roots; Polymer Chemistry; Polymers; Process; Prodrugs; Property; Publications; Rattus; Research Institute; Self-Help Devices; Signal Transduction; Swelling; Technology; Thinness; Time; Tissue Engineering; Tissues; Veterans; Work; antioxidant therapy; base; biomaterial compatibility; brain tissue; central nervous system injury; controlled release; design; electric impedance; hydrophilicity; implantation; improved; in vivo; in vivo Model; innovation; macrophage; mechanical properties; neuron loss; neuronal survival; neuroprosthesis; neuroprotection; novel; performance site; relating to nervous system; response

This application aims to create innovative polymer coatings to improve intracortical microelectrode biocompatibility. Following intracortical microelectrode implantation, an inflammatory response leads to neuronal loss and the formation of a glial scar around the implant. The loss of neurons and the formation of the glial scar lead to diminished recordings of nearby neurons over time. Biomaterial coatings have the potential of mitigating the inflammatory and glial scarring response. However, drug release from these biomaterials occurs over short durations (hours/days) and many drug-releasing material coatings are mechanically stiff. We seek to increase the duration of release while reducing the mechanical stiffness of coatings to improve intracortical microelectrode biocompatibility. Over the past several years, our groups have created high molecular weight poly(pro-drug) polymer coatings fabricated from curcumin. Thin films or coatings enable long-lasting release of curcumin (several weeks to months of release), and the coatings are significantly less stiff than microelectrode materials. In pilot studies, poly(pro-curcumin) polymer coatings greatly reduce the lesion size following intracortical implantation, demonstrating the potential promise of our approach. Our guiding hypothesis is that the creation of poly(pro- drug) polymer coatings from curcumin increase neuroprotection to improve the long-term recording capability of electrodes. This project is likely to make significant contributions by developing new biomaterial coatings capable of releasing drug over longer durations. These new poly(pro-drug) polymers could potentially lead to paradigm shifts in both biomaterials and neuroscience research for the treatment of injury following central nervous system injury. More specifically, this project would impact the field of neural recording by enabling longer-term recording, potentially enhancing neuroprosthetic interfaces for Veterans suffering from central nervous system related paralysis.

该应用旨在创建创新的聚合物涂层，以改善皮质内 微电极生物相容性。皮质内微电极植入后，炎症反应 导致神经元损失并在植入物周围形成神经胶质疤痕。神经元的丧失和 随着时间的推移，神经胶质疤痕的形成会导致附近神经元的记录减少。生物材料涂层 具有减轻炎症和神经胶质疤痕反应的潜力。然而，这些药物的释放 生物材料在短时间内（数小时/天）发生，并且许多药物释放材料涂层是 机械刚性。我们寻求增加释放持续时间，同时降低机械刚度 涂层以改善皮质内微电极的生物相容性。 在过去的几年中，我们的团队创造了高分子量聚（前药）聚合物涂层 由姜黄素制成。薄膜或涂层能够持久释放姜黄素（几周后即可释放） 释放几个月），并且涂层的硬度明显低于微电极材料。在试点研究中， 聚（姜黄素原）聚合物涂层大大减小了皮质内植入后的病变大小， 展示我们方法的潜在前景。我们的指导性假设是，聚（亲 药物）姜黄素聚合物涂层可增强神经保护，从而提高长期记录能力 电极。 该项目可能会通过开发能够实现以下功能的新型生物材料涂层做出重大贡献： 较长时间释放药物。这些新的聚（前药）聚合物可能会导致范式 治疗中枢神经损伤的生物材料和神经科学研究的转变 系统损伤。更具体地说，该项目将通过实现长期的记录来影响神经记录领域 记录，可能增强患有中枢神经系统疾病的退伍军人的神经假体接口 相关的瘫痪。