No abstract

Tumor progression relies on the interaction between neoplastic epithelial cells and their surrounding stromal partners. This cell cross-talk affects stromal development, and ultimately the heterogeneity impacts drug efficacy. To mimic this evolving paradigm, 3D vascularized pancreatic adenocarcinoma tissue is microengineered in a tri-culture system composed of patient-derived pancreatic organoids, human fibroblasts, and endothelial cells on a perfusable platform, situated in a 96-well plate. Through synergistic engineering, the benefits of cellular fidelity of patient tumor organoids are combined with the flow control of an organ-on-a-chip platform. Validation of this platform includes demonstrating the growth of pancreatic tumor organoids by monitoring the change in metabolic activity of the tissue. Investigation of the tumor microenvironment highlights the role of fibroblasts in symbiosis with patient organoids, resulting in a sixfold increase of collagen deposition and corresponding increase in tissue stiffness in comparison to fibroblast free controls. The value of a perfusable vascular network is evident in drug screening, as perfusing gemcitabine into stiffened matrix does not show the dose-dependent effects on decrease in tumor viability as those under static conditions. These findings demonstrate the importance of a dynamic synergistic relationship between patient cells with stromal fibroblasts, in a 3D perfused vascular network, to accurately recapitulate a dynamic tumor microenvironment.

Inspired by the collective intelligence in natural swarms, microrobotic agents have been controlled to form artificial swarms for targeted drug delivery, enhanced imaging, and hyperthermia. Different from these well-investigated tasks, this work aims to develop microrobotic swarms for embolization, which is a clinical technique used to block blood vessels for treating tumors, fistulas, and arteriovenous malformations. Magnetic particle swarms were formed for selective embolization to address the low selectivity of the present embolization technique that is prone to cause complications such as stroke and blindness. We established an analytical model that describes the relationships between fluid viscosity, flow rate, branching angle, magnetic field strength, and swarm integrity, based on which an actuation strategy was developed to maintain the swarm integrity inside a targeted region under fluidic flow conditions. Experiments in microfluidic channels, ex vivo tissues, and in vivo porcine kidneys validated the efficacy of the proposed strategy for selective embolization.

Understanding biological systems and mimicking their functions require electronic tools that can interact with biological tissues with matched softness. These tools involve biointerfacing materials that should concurrently match the softness of biological tissue and exhibit suitable electrical conductivities for recording and reading bioelectronic signals. However, commonly employed intrinsically soft and stretchable materials usually contain solvents that limit stability for long-term use or possess low electronic conductivity. To date, an ultrasoft (i.e., Young’s modulus <30 kPa), conductive, and solvent-free elastomer does not exist. Additionally, integrating such ultrasoft and conductive materials into electronic devices is poorly explored. This article reports a solvent-free, ultrasoft and conductive PDMS bottlebrush elastomer (BBE) composite with single-wall carbon nanotubes (SWCNTs) as conductive fillers. The conductive SWCNT/BBE with a filler concentration of 0.4 − 0.6 wt% reveals an ultralow Young’s modulus (<11 kPa) and satisfactory conductivity (>2 S/m) as well as adhesion property. Furthermore, we fabricate ultrasoft electronics based on laser cutting and 3D printing of conductive and non-conductive BBEs and demonstrate their potential applications in wearable sensing, soft robotics, and electrophysiological recording.

The heart completes a complex set of tasks, including the initiation or propagation of an electrical signal with regularity (proper heart rate and rhythm) and generating sufficient force of contraction (contractility). Probing mechanisms of heart diseases and quantifying drug efficacies demand a platform that is capable of continuous operation inside a cell incubator for long-term measurement of cardiomyocyte (CM) monolayers. Here, we report a microdevice array that is capable of performing continuous, long-term (14 days) measurement of contractility, beating rate, and beating rhythm in a monolayer of human-induced pluripotent stem cell-CMs (hiPSC-CMs). The device consists of a deformable membrane with embedded carbon nanotube (CNT)-based strain sensors. Contraction of the hiPSC-CMs seeded on the membrane induces electrical resistance change of the CNT strain sensor. Continuously reading the sensor signals revealed that hiPSC-CMs started to beat from day 2 and plateaued on day 5. Average contractile stress generated by a monolayer of hiPSC-CMs was determined to be 2.34 ± 0.041 kPa with a beating rate of 1.17 ± 0.068 Hz. The device arrays were also used to perform comprehensive measurement of the beating rate, rhythm, and contractility of the hiPSC-CMs and quantify the cell responses to different concentrations of agonists and antagonists, which altered the average contractile stress to the range of 1.15 ± 0.13 to 3.96 ± 0.53 kPa. The continuous measurement capability of the device arrays also enabled the generation of Poincaré plots for revealing subtle changes in the beating rhythm of hiPSC-CMs under different drug treatments.