Abstract 4361877: Bismuth Nanoparticle-Infused Bioresorbable Graft Enables Multimodal Computed Tomography and Photoacoustic Imaging-Based Monitoring and Promotes Vascular Regeneration

Abstract

Background: Bioresorbable polymeric grafts lack capabilities for non-invasive long-term monitoring, leading to late detection of complications like stenosis or aneurysm. Hence, we engineered a bioresorbable graft from poly(ε-caprolactone) (PCL) and bismuth nanoparticles (BiNPs). BiNPs are active on computed tomography (CT) and photoacoustic (PA) imaging, an emerging adjunct to ultrasound (US). This enables multimodal surveillance of placement, integrity, and resorption, offering the ability to assess performance, monitor regeneration, and facilitate timely intervention. Hypothesis: BiNP infusion would provide sustained, multimodal imaging capabilities without negatively impacting the graft's biocompatibility and capacity to support vascular regeneration. Methods: Synthesized BiNPs were infused into PCL to fabricate grafts via electrospinning. Grafts (autologous control, PCL, PCL-BiNP) were implanted in the abdominal aorta of Sprague Dawley rats (n=3 per group). Imaging was performed over 12 weeks. At 12 weeks, harvested grafts underwent multiplex immunofluorescence and spatial analysis of key vascular cell populations using Halo 4.0. Statistical significance was defined as p<0.05. Results: BiNP infusion reduced the grafts’ fiber diameter and pore area but maintained hemocompatibility, non-cytotoxicity, and maximum stress comparable to rat aorta. Over 12 weeks, the BiNP-infused grafts enabled serial in vivo monitoring via CT and US/PA imaging, achieved through the gradual release of BiNPs during graft resorption, which occurred without systemic organ accumulation. All grafts also exhibited comparable patency and flow characteristics. At week 12, PCL and PCL-BiNP showed endothelialization, cell density, and collagen content comparable to control. Spatial analysis revealed a confluent endothelial layer on the lumen of electrospun grafts and high-density smooth muscle cell clusters in the developing medial layer, indicating structured neotissue formation. PCL and PCL-BiNP grafts exhibited greater, diffuse immune cell and fibroblast densities than control, consistent with active macrophage resorption and early vascular remodeling. Overall, spatial patterns were similar between PCL and PCL-BiNP grafts, showing BiNP infusion enhanced monitoring without impairing regeneration. Conclusion: Novel BiNP-infused bioresorbable graft facilitates non-invasive serial monitoring via CT and US/PA imaging, while maintaining in vivo performance comparable to autologous grafts.