Photocrosslinked hydrogels, such as methacrylate‐modified gelatin (gelMA) and hyaluronic acid (HAMA), are widely utilized as tissue engineering scaffolds and/or drug delivery vehicles, but lack a suitable means for noninvasive, longitudinal monitoring of surgical placement, biodegradation, and drug release. Therefore, a novel photopolymerizable X‐ray contrast agent, methacrylate‐modified gold nanoparticles (AuMA NPs), is developed to enable covalent‐linking to methacrylate‐modified hydrogels (gelMA and HAMA) in one‐step during photocrosslinking and noninvasive monitoring by X‐ray micro‐computed tomography (micro‐CT). Hydrogels exhibit a linear increase in X‐ray attenuation with increased Au NP concentration to enable quantitative imaging by contrast‐enhanced micro‐CT. The enzymatic and hydrolytic degradation kinetics of gelMA‐Au NP hydrogels are longitudinally monitored by micro‐CT for up to 1 month in vitro, yielding results that are consistent with concurrent measurements by optical spectroscopy and gravimetric analysis. Importantly, AuMA NPs do not disrupt the hydrogel network, rheology, mechanical properties, and hydrolytic stability compared with gelMA alone. GelMA‐Au NP hydrogels are thus able to be bioprinted into well‐defined 3D architectures supporting endothelial cell viability and growth. Overall, AuMA NPs enable the preparation of both conventional photopolymerized hydrogels and bioprinted scaffolds with tunable X‐ray contrast for noninvasive, longitudinal monitoring of placement, degradation, and NP release by micro‐CT.
Vascular atresia are often treated via transcatheter recanalization or surgical vascular anastomosis due to congenital malformations or coronary occlusions. The cellular response to vascular anastomosis or recanalization is, however, largely unknown and current techniques rely on restoration rather than optimization of flow into the atretic arteries. An improved understanding of cellular response post anastomosis may result in reduced restenosis. Here, an in vitro platform is used to model anastomosis in pulmonary arteries (PAs) and for procedural planning to reduce vascular restenosis. Bifurcated PAs are bioprinted within 3D hydrogel constructs to simulate a reestablished intervascular connection. The PA models are seeded with human endothelial cells and perfused at physiological flow rate to form endothelium. Particle image velocimetry and computational fluid dynamics modeling show close agreement in quantifying flow velocity and wall shear stress within the bioprinted arteries. These data are used to identify regions with greatest levels of shear stress alterations, prone to stenosis. Vascular geometry and flow hemodynamics significantly affect endothelial cell viability, proliferation, alignment, microcapillary formation, and metabolic bioprofiles. These integrated in vitro-in silico methods establish a unique platform to study complex cardiovascular diseases and can lead to direct clinical improvements in surgical planning for diseases of disturbed flow.
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