Multimodal Imaging Compatible Micro-Physiological System

Three dimensional (3D) printed perfused tissue models are gaining attention due to promise of reproducing patient-specific pathology. We present here the design and characterization of a novel multimodal imaging compatible micro-physiological system (MicMPS) that contains three innovative features: (1) a perfused 4.5 mL enclosure volume for generating large tissue-mimicking 3D cellular systems comparable to rodent sizes, (2) ability to take ‘biopsy-like’ samples for non-destructive longitudinal interrogation of tissue composition, and (3) compatibility with cross-sectional, high-resolution imaging modalities, including computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound (US), for longitudinal and functional assessments of MicMPS and enclosed tissue architecture. Contrast-enhanced micro-CT imaging was employed to investigate MicMPS architecture and demonstrate reproducibility in fabrication process. MicMPS perfusion was examined using dynamic contrast-enhanced MRI performed on a low-cost permanent MR magnet scanner. As a proof-of-concept, fibroblasts-laden MicMPS was developed and maintained under perfusion for 5 days. Evaluation of cell viability and perfusion was performed across the entire MicMPS. US image-guided biopsy was performed to obtain engineered tissue for microscopic analysis, thus demonstrating non-destructive capabilities for interim MicMPS interrogation. The newly designed MicMPS bridges the gap between microfluidic systems and animal studies, providing the controlled environment of a cell culture system while enabling imaging investigations that are routinely performed in animal studies.