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.