Biology subjects

Floryan, M.

Publications and source records attributed to Floryan, M..

3 recordsLinked to original sources

bioRxiv2026

IntravChip: a vascularized and perfused microfluidic model of the primary tumor microenvironment to collect intravasated tumor cells

Hematogenous metastasis is initiated when tumor cells (TCs) intravasate into the vasculature, yet intravasation remains poorly understood because it is difficult to observe in vivo and intravasated TCs are challenging to isolate. To address these challenges, we developed IntravChip, a continuously perfused microfluidic platform containing a vascularized primary tumor microenvironment (TME) enabling the observation of TC intravasation, and a downstream chamber to collect intravasated TCs. The IntravChip can support a high TC concentration in the TME while maintaining complete vascular perfusion, which we found was necessary to collect intravasated cells. Using MDA-MB-231 breast TCs, we identified an optimal initial TC seeding density that, by day 9, yields a densely populated TME and 100-440 collected intravasated TCs. We validated the IntravChip across several TC types, showing that MDA-MB-231 and MV3 TCs have the highest intravasation rates while MCF-7 TCs have low intravasation efficiency. We also show that the IntravChip is compatible with super-resolution nano-imaging. Our devices enabled high-quality STORM imaging, which revealed that H3K9me3 nanodomains are significantly differentially distributed in intravasated MDA-MB-231 tumor cells compared to those residing in the TME. Finally, the IntravChip was validated as a platform to test the effects of anti-cancer drugs on tumor cells and on the vasculature. We showed that a 5 M concentration of sorafenib reduced intravasation events by 69% without impacting the morphology of the microvascular networks (MVNs), while a 10 M concentration led to a significant decrease in vessel diameter. This platform enables quantitative analysis of TC intravasation, collection of intravasated TCs for characterization, and screening of anti-metastatic therapies.

bioengineering↗

bioRxiv2025

Measuring Perfusion Pressure and Flow Resistance in a Microfluidic Device Using an External Optical System

The pathology of human diseases are now investigated using microphysiological systems (MPS) supporting vascular structures. Efforts to increase physiological relevance of these platforms have centered on the incorporation of organ-specific cellular and non-cellular constituents. However, tissue-specific cellular constituents must experience appropriate physical forces to faithfully replicate physiological function. Quantification of physical forces in MPS has received little attention. The goal of this study was to establish a simple and robust system capable of interfacing with existing pumps to quantitatively characterize the flow delivered to a MPS. The system assessed both the fluid pressure driving flow through a microphysiological platform and the resistance to flow of glass capillary tubes or a model vascular network. The system showed excellent qualitative and quantitative agreement with resistance values measured by a hydrostatic approach and predicted for laminar flow through a smooth capillary tube. Importantly, the system is optically-based without sensors contacting the circulating fluid making it ideally-suited for long-term biological studies where sterility is paramount. Benchmarking experiments were supplemented with measurements of driving pressure and flow resistance from vascular structures within a MPS in a humidified incubator. Vascular resistance measurements were consistent with published results obtained from similar microvascular networks.

bioengineering↗

bioRxiv2025

Remodeling of self-assembled microvascular networks under long term flow

The incorporation of a functional perfusable microvascular network (MVN) is a common requirement for most organ on-chip-models. Long-term perfusion of MVNs is often required for the maturation of organ phenotypes and disease pathologies and to model the transport of cells and drugs entering organs. In our microphysiological system, we observe that flow can recover perfusion in regressed MVNs and maintain perfusable MVNs for at least 51 days. Throughout the 51 days, however, the MVNs are continuously remodeling to align with the direction of bulk flow and only appear to attain morphological homeostasis with the use of maintenance medium without growth factors. We observed that the flow resistance of the MVNs decreases over time, and using a computational model, we show that stable vessels have higher flow rates and velocities compared to regressing vessels. Cytokine analysis suggests that static conditions generate an inflammatory state, and that continuous flow reduces inflammation over an extended period. Finally, through bulk RNA sequencing we identify that both the endothelial and fibroblast cells are actively engaged in vascular and matrix remodeling due to flow and that these effects persist for at least 2 weeks. This MPS can be applied to study hemodynamically driven processes, such as metastatic dissemination or drug distribution, or to model long-term diseases previously not captured by MPS, such as chronic inflammation or aging-associated diseases.

biophysics↗