R01EB029418

Evaluation of Tantalum Oxide Nanoparticles for In Vivo X-Ray Computed Tomography Evaluation of Implantable Biomaterials - 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. Furthermore, 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. 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. We will determine 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. We will measure in vivo biodegradation and evaluate 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.

Michigan State University

NOT APPLICABLE

93.286 - Discovery and Applied Research for Technological Innovations to Improve Human Health

National Institute of Biomedical Imaging and Bioengineering (NIBIB) [HHS - NIH]

East Lansing, Michigan 488242600 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the End Date has been extended from 11/30/24 to 04/30/29 and the total obligations have increased 734% from $383,367 to $3,196,306.