Evaluation of tantalum oxide nanoparticles for in vivo X-ray computed tomography evaluation of implantable biomaterials

氧化钽纳米颗粒用于植入式生物材料体内 X 射线计算机断层扫描评估的评估

• 批准号: 10326392
• 负责人: Erik Shapiro
• 金额: $ 47.51万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-06 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10326392
• 关键词: 3-Dimensional; Academia; Acid Fast Bacillae Staining Method; Axon; Bilateral; Biocompatible Materials; Biodegradation; Biological; Biological Assay; Bismuth; Carrageenan; Cells; Clinical; Collection; Connective Tissue; Contrast Media; Coupled; Data; Data Analyses; Development; Effectiveness; Environment; Evaluation; Exhibits; Gadolinium; Glycolates; Goals; Grant; Greater sac of peritoneum; Histology; Hospitals; Human; Image; Immune; Implant; In Vitro; Industry; Inflammation; Knowledge; Length; Limb structure; Location; Measurement; Measures; Mechanics; Methodology; Microscopy; Modeling; Monitor; Mus; Nerve; Nerve Regeneration; Optics; Outcome; Pathology; Patients; Performance; Peripheral nerve injury; Physiological; Physiology; Polymers; Porosity; Property; Protocols documentation; Radiation; Radiology Specialty; Rattus; Regenerative Medicine; Resolution; Roentgen Rays; Scanning; Site; Skin; Spinal nerve structure; System; Techniques; Tensile Strength; Testing; Tissue Embedding; Tissue Engineering; Tissues; Toxic effect; Toxicology; Tube; X-Ray Computed Tomography; biodegradable polymer; biomaterial compatibility; bone; clinical translation; clinically translatable; contrast imaging; design; high resolution imaging; imaging modality; imaging system; implantation; in vivo; innovation; microCT; nanoparticle; outer space; physical property; polycaprolactone; pre-clinical; reconstruction; relating to nervous system; research and development; scaffold; sciatic nerve injury; serial imaging; subcutaneous; systems research; tantalum oxide; tissue regeneration; translation to humans; translational study

Project Abstract This grant proposes both an innovative contrast agent and X-ray computed tomography (CT) imaging method for monitoring implantable biomaterials, in vivo. Tissue engineered scaffolds (TES) are a regenerative medicine paradigm that create 3D environments to induce tissue formation in a variety of tissues, including skin, bone, connective tissue and nerves. Key to TES research and development is the ability to measure true in vivo biodegradation rates, and to assess internal microstructure post-implantation. Serial imaging and data analysis can accomplish this in ways that are easier and more reliable than histology. Further, this new contrast agent and imaging method are directly translatable for clinical monitoring of TES structural integrity and location post- implantation in patients. CT is a clinically important radiological technique, affording high resolution scans with safe levels of radiation, with imaging systems in nearly every hospital and radiology department, and preclinical microCT research systems common throughout academia and industry. We have pioneered strategies for using microCT to visualize TES and measure biodegradation in vivo following implantation into mice. Our early studies accomplished this by doping TES with radiopaque gadolinium and bismuth nanoparticles, however, gadolinium and bismuth exhibit compromising toxicity, obviating their clinical translation and continued development. Tantalum oxide (TaOx) has emerged as a more biocompatible alternative, with enhanced CT properties, and so, in this grant, we propose to fully investigate TaOx nanoparticles for enabling in vivo serial imaging of biomaterials and TES. We have extensive preliminary data on the facile incorporation of TaOx nanoparticles into polymer TES for nerve regeneration, with a robust microCT imaging and analysis protocol. In Aim 1 we will fabricate and characterize a collection of polymer TES with varying TaOx content and degradation rates, with well characterized properties. A battery of in vitro assessments will be performed with the goal of maximizing TaOx content while minimally impacting physical properties or causing adverse toxicity. In Aim 2 we will demonstrate the usefulness of microCT of TaOx-embedded biodegradable TES by measuring the true in vivo biodegradation of TaOx-embedded polymer TES implanted in varying physiological milieu, determining 1) the effect of implantation site physiological milieu on TES biodegradation rate, and 2) how well in vitro degradation studies predict in vivo biodegradation and TES integrity. In Aim 3 we will determine the in vivo impact of TaOx by evaluating the in vivo performance of TaOx-embedded biodegradable TES for promoting functional nerve regrowth in peripheral nerve injury, measuring in vivo biodegradation and evaluating potential toxicity. Successful demonstration of functional nerve regrowth with TaOx-embedded PLGA TES will rationalize translational studies towards in vivo CT evaluation of TaOx-embedded TES in humans.

项目摘要 该赠款提出了创新的对比剂和X射线计算机断层扫描（CT）成像方法 用于监测体内的可植入生物材料。组织工程脚手架（TES）是一种再生医学 创建3D环境以诱导各种组织中的组织形成的范式，包括皮肤，骨头， 结缔组织和神经。 TES研发的关键是能够在体内衡量真实的能力 生物降解率，并评估植入后内部微观结构。串行成像和数据分析 可以以比组织学更容易，更可靠的方式来实现这一目标。此外，这个新的对比代理 和成像方法是可以直接翻译的，可用于临床监测结构完整性和位置。 患者植入。 CT是一种临床上重要的放射学技术，可提供具有安全辐射水平的高分辨率扫描， 在几乎每个医院和放射科的成像系统以及临床前微区研究 整个学术界和工业的系统。我们有使用Microct的开创性策略 可视化TE并在植入小鼠后体内测量生物降解。我们的早期研究 但是，通过掺有radiopaque gadolinium和bismuth纳米颗粒来实现这一目标 二氧化碳表现出损害的毒性，消除了它们的临床翻译和持续发展。 氧化棘塔（Taox）已成为一种更具生物相容性的替代方案，具有增强的CT特性，因此 在这笔赠款中，我们建议全面研究陶氏纳米颗粒，以实现生物材料的体内串行成像 和TES。我们拥有有关陶一纳米颗粒便利掺入聚合物的广泛初步数据 TES用于神经再生，具有鲁棒的MicroCT成像和分析方案。 在AIM 1中，我们将制造和表征具有不同陶氏含量和不同的聚合物TE 降解速率，具有良好的特性。将进行一系列体外评估 最大程度地利用陶氏含量的目标，同时最大程度地影响物理特性或引起不良毒性。 在AIM 2中，我们将通过测量来证明Taox包裹的可生物降解TE的Microct的实用性 植入不同生理环境中的汤毒的聚合物TE的真实体内生物降解， 确定1）植入部位生理环境对TES生物降解率的影响，以及2） 体外降解研究预测体内生物降解和完整性。在AIM 3中，我们将确定体内 通过评估汤毒片剂的生物降解TE的体内性能来促进陶氏 外周神经损伤中的功能性神经再生，测量体内生物降解并评估潜力 毒性。成功地证明了用陶托包裹的PLGA TES的功能性神经再生能力将合理化 对人类中陶托包裹的TE的体内CT评估的转化研究。