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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

基本信息

批准号：
10548861
负责人：
Erik Shapiro
金额：
$ 44.5万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
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/10548861
关键词：
3-Dimensional Academia 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 Growth 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 Rationalization Rattus Regenerative Medicine Resolution Roentgen Rays Scanning Site Skin Spinal nerve structure Structure System Techniques Tensile Strength Testing Tissue Embedding Tissue Engineering Tissues Toxic effect Toxicology Tube Visualization X-Ray Computed Tomography axon growth biodegradable polymer biomaterial compatibility bone clinical translation contrast imaging design high resolution imaging imaging modality imaging system implantation in vivo innovation microCT nanoparticle neural outer space physical property polycaprolactone pre-clinical reconstruction research and development scaffold sciatic nerve injury serial imaging subcutaneous systems research tantalum oxide tissue regeneration translation to humans translational study

项目摘要

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