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

项目摘要 这笔赠款提出了一种创新的造影剂和X射线计算机体层摄影(CT)成像方法 用于体内可植入生物材料的监测。组织工程支架是一种再生医学 创建3D环境以在各种组织中诱导组织形成的范例，包括皮肤、骨骼、 结缔组织和神经。TES研究和开发的关键是在体内测量真值的能力 生物降解率，并评估植入后的内部微观结构。连续成像和数据分析 可以用比组织学更容易、更可靠的方式来实现这一点。此外，这种新的造影剂 和成像方法可直接用于TES术后结构完整性和定位的临床监测 在患者身上植入。 CT是临床上重要的放射学技术，提供具有安全辐射水平的高分辨率扫描， 几乎每个医院和放射科都有成像系统，以及临床前的微型CT研究 整个学术界和工业界都普遍使用的系统。我们已经开创了使用微CT的策略 可视化TES并测量植入小鼠体内后的生物降解性。我们早期的研究 这是通过在TES中掺杂不透射线的Gd和铋纳米颗粒来实现的，然而，Gd 和铋表现出折衷的毒性，阻碍了它们的临床翻译和持续开发。 氧化钽(TaOx)已经成为一种更具生物相容性的替代品，具有增强的CT性能，因此， 在这笔赠款中，我们建议全面研究TaOx纳米颗粒，使其能够在体内连续成像生物材料 还有TES。我们有大量的初步数据表明TaOx纳米粒子可以轻松地并入聚合物中。 TES用于神经再生，具有强大的MicroCT成像和分析方案。 在目标1中，我们将制造和表征一系列具有不同TaOx含量和 降解率，具有良好的特性。一系列的体外评估将在 目标是最大限度地提高TaOx含量，同时将对物理性能的影响降至最低或造成不良毒性。 在目标2中，我们将通过测量TaOx包埋的可生物降解TES的MicroCT来证明其有用性 TaOx包埋聚合物TES在不同生理环境中的真正体内生物降解， 确定1)植入部位的生理环境对TES生物降解率的影响，以及2)植入的效果如何 体外降解研究预测体内的生物降解和TES的完整性。在目标3中，我们将确定体内的 评价TaOx包埋生物可降解TES的体内性能对TaOx的影响 周围神经损伤后功能性神经再生的体内生物降解性测定及潜能评价 毒性。TaOx包埋PLGA TES成功演示功能性神经再生将合理化 TaOx包埋TES体内CT评价的翻译研究。

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.