Biology subjects

Savoji, H.

Publications and source records attributed to Savoji, H..

3 recordsLinked to original sources

bioRxiv2025

Patient-Specific 3D Heart-On-a-Chip Model of Dilated Cardiomyopathy with Embedded Bead-Based Mapping of Tissue Contractility

Dilated cardiomyopathy (DCM) is the leading cause of heart transplantation, with a 50% risk of progression to heart failure within five years. Conventional disease modeling approaches fail to recapitulate the sophisticated function of the human heart. Alternatively, heart-on-a-chip (HOC) platforms enable real-time monitoring of disease progression and drug responses using miniaturized engineered heart tissues. Here, we developed a functional HOC model using patient-specific human induced pluripotent stem cells (hiPSCs), reprogrammed from the patients blood samples. The chip contains two cell-seeding chambers with flexible silicone pillars to support tissue formation. Healthy and DCM hiPSCs were differentiated into cardiomyocytes, combined with an optimized ratio of human cardiac fibroblasts, encapsulated in a fibrin/Geltrex hydrogel (containing fluorescent beads), and seeded in the device chambers. The tissue gradually compacted and started beating spontaneously. Immunofluorescence assay revealed structural abnormalities in DCM tissues, including reduced cell alignment and elongation. The tissue functional responses (e.g., calcium transients and beating) were investigated after 2 weeks of culture, revealing ventricular tachycardia in DCM tissue and highlighting functional hallmarks of the disease. Finally, the model was validated using a drug with known inotropic and chronotropic effects (i.e., norepinephrine). Our platform demonstrated great potential in drug screening, disease modeling, and personalized medicine.

bioengineering↗

bioRxiv2025

Heart-On-a-Chip with Integrated Ultrasoft Mechanosensors for Continuous Measurement of Cell- and Tissue-scale Contractile Stresses

Heart-on-a-chip platforms aim to miniaturize and replicate the complex structure and function of cardiac tissue. Traditionally, microfabricated pillar pairs have been employed in these systems to provide tissue anchorage and determine contractility parameters based on pillar deflection. However, this approach lacks the spatial resolution required to capture local cell- and tissue-scale mechanical stresses. In this study, we established a non-destructive optical method for continuous micro- and macro-scale contractile force measurements. We utilized our previously developed edge-labeled micro-spherical stress gauges (eMSGs) to map the stresses within a heart-on-a-chip. These ultrasoft mechanosensors visibly deform in response to stresses generated by cells and the extracellular matrix (ECM). The chip consisted of two cell-seeding chambers, each containing flexible silicone pillar pairs to support tissue formation and compaction. Neonatal rat cardiomyocytes (CMs) were encapsulated in a fibrin/Geltrex hydrogel mixture containing eMSGs and seeded into each chamber. Over time, the tissue compacted and began beating spontaneously, demonstrating structural alignment and functional cardiac hallmarks, such as calcium transients and tissue-scale beating. The effects of ECM composition on tissue function were examined, revealing that lower fibrin concentrations significantly enhanced contractile frequency, regularity, and stress generation. Local cell- and ECM-scale mechanics were further investigated by analyzing the shape changes of the dispersible sensors. Lateral and longitudinal stresses were calculated for each sensor, highlighting the critical role of tissue compaction and contraction in cell-generated forces. Finally, the platform was validated using two known drug candidates, with their effects on contractility clearly demonstrated.

bioengineering↗

bioRxiv2023

High-Resolution Additive Manufacturing of a Biodegradable Elastomer with a Low-Cost LCD 3D Printer

Artificial organs and organs-on-a-chip are of great clinical and scientific interest and have recently been made by additive manufacturing, but depend on, and benefit from, biocompatible, biodegradable, and soft materials. Poly(octamethylene maleate (anhydride) citrate (POMaC) meets these criteria and has gained popularity, and as in principle, it can be photocured and is amenable to vat-photopolymerization (VP) 3D printing, but only low-resolution structures have been produced so fa. Here, we introduce a VP-POMaC ink and demonstrate 3D printing of high resolution (80 {micro}m) and complex 3D structures using low-cost ([~]US$300) liquid-crystal display (LCD) printers. The ink includes POMaC, a diluent and porogen additive to reduce viscosity within the range of VP, and a crosslinker to speed up reaction kinetics. The mechanical properties of the cured ink were tuned to match the elastic moduli of different tissues simply by varying the porogen concentration. The biocompatibility was assessed by cell culture which yielded 80% viability and the potential for tissue engineering illustrated with a 3D printed gyroid seeded with cells. VP-POMaC and low-cost LCD printers make the additive manufacturing of high resolution, elastomeric, and biodegradable constructs widely accessible, paving the way for a myriad of applications in tissue engineering, implants, organ-on-a-chip, wearables, and soft robotics.

bioengineering↗