Biology subjects

Mansouri, M.

Publications and source records attributed to Mansouri, M..

10 recordsLinked to original sources

bioRxiv2026

Design and Application of a μSiM Outer Blood-Retinal Barrier (OBRB) Model as a Drug Development Tool

The outer blood-retinal barrier (OBRB) is the primary interface through which systemically circulating drugs reach the retina. A tool that measures delivery across this barrier would support the development of targeted therapies as alternatives to repeated intravitreal injection, and the screening of drugs that reach the retina as an off-target toxicity. Such a tool should deliver drugs fluidically through a vascular compartment, measure transport across the retinal pigment epithelium (RPE), and display disease phenotypes relevant to efficacy. Here we adapt the SiM platform, which places epithelium and endothelium in direct juxtaposition across a permeable, optically transparent silicon nitride nanomembrane. ARPE-19 and human umbilical vein endothelial cells (HUVECs) were used as development cell sources. ARPE-19 monocultures reached a transepithelial electrical resistance of 68 {+/-} 26 {Omega} cm2 by 28 days, and ARPE-19 + HUVEC co-cultures reached a small-molecule permeability of 6.34 {+/-} 1.3 x 10-4 cm min-1 within 14 days, a state reported elsewhere only after longer culture. The barriers developed an intervening basement membrane. Drugs perfused through the basal vascular channel crossed into an open apical well, where sampling and mass spectrometry showed transport correlating with lipophilicity, as reported in vivo. The device also displayed two clinically relevant phenotypes. Digoxin at a clinically toxic concentration reduced viability in the co-barrier by about half and doubled permeability. In a vascularized configuration, VEGF drove endothelial invasion of the RPE layer, as seen in neovascular AMD. The SiM-OBRB therefore satisfies basic design criteria for measurement of drug bioavailability, toxicity, and efficacy.

bioengineering↗

bioRxiv2026

Modular Integration of Impedance Sensing for Real-Time Assessment of Barrier Integrity

Microphysiological systems (MPS) are essential for modeling tissue barriers, yet integrating electrical readouts often requires permanently sealed microfluidic architectures that limit access to open-well (direct-access) workflows used in bioscience laboratories. To resolve this issue, we present a modular approach in which functional components are added and removed from a standard MPS core using a magnetic interface. This design preserves compatibility with established open-well protocols for seeding and downstream analysis, while microfluidic perfusion or electrical sensing capabilities are added only when needed. We demonstrate this approach with an impedance-sensing module that enables continuous impedance measurements to assess barrier function. By fitting spectra to an equivalent circuit model, we quantify junctional and non-junctional electrical contributions to barrier integrity over time, alongside conventional single-frequency TEER, and complementary permeability and imaging readouts. We apply this platform across three representative use cases, including LPS-induced disruption, shear stress-mediated strengthening, and compatibility with barrier models formed above a 3D hydrogel matrix.

bioengineering↗

bioRxiv2025

Medical Abbreviation Disambiguation with Large Language Models: Zero- and Few-Shot Evaluation on the MeDAL Dataset

Abbreviation disambiguation is a critical challenge in processing clinical and biomedical texts, where ambiguous short forms frequently obscure meaning. In this study, we assess the zero-shot performance of large language models (LLMs) on the task of medical abbreviation disambiguation using the MeDAL dataset, a large-scale resource constructed from PubMed abstracts. Specifically, we evaluate GPT-4 and LLaMA models, prompting them with contextual information to infer the correct long-form expansion of ambiguous abbreviations without any task-specific fine-tuning. Our results demonstrate that GPT-4 substantially outperforms LLaMA across a range of ambiguous terms, indicating a significant advantage of proprietary models in zero-shot medical language understanding. These findings suggest that LLMs, even without domain-specific training, can serve as effective tools for improving readability and interpretability in biomedical NLP applications.

bioinformatics↗

bioRxiv2024

Fluid Flow Impacts Endothelial-Monocyte Interactions in a Model of Vascular Inflammatory Fibrosis

The aberrant vascular response associated with tendon injury results in circulating immune cell infiltration and a chronic inflammatory feedback loop leading to poor healing outcomes. Studying this dysregulated tendon repair response in human pathophysiology has been historically challenging due to the reliance on animal models. To address this, our group developed the human tendon-on-a-chip (hToC) to model cellular interactions in the injured tendon microenvironment; however, this model lacked the key element of physiological flow in the vascular compartment. Here, we leveraged the modularity of our platform to create a fluidic hToC that enables the study of circulating immune cell and vascular crosstalk in a tendon injury model. Under physiological shear stress consistent with postcapillary venules, we found a significant increase in the endothelial leukocyte activation marker intercellular adhesion molecule 1 (ICAM-1), as well as enhanced adhesion and transmigration of circulating monocytes across the endothelial barrier. The addition of tissue macrophages to the tendon compartment further increased the degree of circulating monocyte infiltration into the tissue matrix. Our findings demonstrate the importance of adding physiological flow to the human tendon-on-a-chip, and more generally, the significance of flow for modeling immune cell interactions in tissue inflammation and disease.

bioengineering↗

bioRxiv2023

Microengineering 3D Collagen Matrices with Tumor-Mimetic Gradients in Fiber Alignment

In the tumor microenvironment (TME), collagen fibers facilitate tumor cell migration through the extracellular matrix. Previous studies have focused on studying the responses of cells on uniformly aligned or randomly aligned collagen fibers. However, the in vivo environment also features spatial gradients in alignment, which arise from the local reorganization of the matrix architecture due to cell-induced traction forces. Although there has been extensive research on how cells respond to graded biophysical cues, such as stiffness, porosity, and ligand density, the cellular responses to physiological fiber alignment gradients have been largely unexplored. This is due, in part, to a lack of robust experimental techniques to create controlled alignment gradients in natural materials. In this study, we image tumor biopsy samples and characterize the alignment gradients present in the TME. To replicate physiological gradients, we introduce a first-of-its-kind biofabrication technique that utilizes a microfluidic channel with constricting and expanding geometry to engineer 3D collagen hydrogels with tunable fiber alignment gradients that range from sub-millimeter to millimeter length scales. Our modular approach allows easy access to the microengineered gradient gels, and we demonstrate that HUVECs migrate in response to the fiber architecture. We provide preliminary evidence suggesting that MDA-MB-231 cell aggregates, patterned onto a specific location on the alignment gradient, exhibit preferential migration towards increasing alignment. This finding suggests that alignment gradients could serve as an additional taxis cue in the ECM. Importantly, our study represents the first successful engineering of continuous gradients of fiber alignment in soft, natural materials. We anticipate that our user-friendly platform, which needs no specialized equipment, will offer new experimental capabilities to study the impact of fiber-based contact guidance on directed cell migration.

bioengineering↗

bioRxiv2022

A Miniaturized 3D-Printed Pressure Regulator (μPR) for Microfluidic Cell Culture Applications

Controlled fluid flows are the hallmark feature of microfluidic culture systems and provide precise definition over the biophysical and biochemical microenvironment. Flow control is commonly achieved using displacement-based (e.g., syringe or peristaltic pumps) or pressure-based techniques. These methods offer complex flow capabilities but can be challenging to integrate into incubators or other confined environments due to their large form factors and accompanying peripheral equipment. Since many microfluidic cell culture studies use a single controlled flow rate to maintain or stimulate cells, a portable flow control platform that fits easily into an incubator will benefit the microfluidic community. Here, we demonstrate that a tunable, 3D printed micro pressure regulator (PR), combined with a battery-powered miniature air pump, can operate as a stand-alone pneumatic flow control platform for microfluidic applications. We detail the design and fabrication of the PR and demonstrate: i) a tunable outlet pressure range relevant for microfluidic applications (1-10 kPa), ii) highlight dynamic control in a microfluidic network, and iii) maintain human umbilical vein endothelial cells (HUVECs) in a multi-compartment membrane-based culture device under continuous flow conditions. We anticipate that our 3D-printed fabrication approach and open access designs will allow other laboratories to rapidly customize PRs to support a broad range of applications.

bioengineering↗

bioRxiv2022

The Modular μSiM: a Mass Produced, Rapidly Assembled, and Reconfigurable Platform for the Study of Barrier Tissue Models In Vitro

Advanced in vitro tissue chip models can reduce and replace animal experimentation and may eventually support on-chip clinical trials. To realize this potential, however, tissue chip platforms must be both mass-produced and reconfigurable to allow for customized design. To address these unmet needs, we introduce an extension of our {micro}SiM (microdevice featuring a silicon-nitride membrane) platform. The modular {micro}SiM (m-{micro}SiM) uses mass-produced components to enable rapid assembly and reconfiguration by laboratories without knowledge of microfabrication. We demonstrate the utility of the m-{micro}SiM by establishing an hiPSC-derived blood-brain barrier (BBB) in bioengineering and non-engineering, brain barriers focused laboratories. We develop and validate in situ and sampling-based assays of small molecule diffusion as a measure of barrier function. BBB properties show excellent interlaboratory agreement and match expectations from literature, validating the m-{micro}SiM as a platform for barrier models and demonstrating successful dissemination of components and protocols. We then demonstrate the ability to quickly reconfigure the m-{micro}SiM for co-culture and immune cell transmigration studies through addition of accessories and/or quick exchange of components. Because the development of modified components and accessories is easily achieved, custom designs of the m-{micro}SiM should be accessible to any laboratory desiring a barrier-style tissue chip platform.

bioengineering↗

bioRxiv2022

The Modular μSiM Reconfigured: Integration of Microfluidic Capabilities to Study in vitro Barrier Tissue Models under Flow

Microfluidic approaches to study tissue barriers have emerged to address the lack of fluid flow in conventional "open-well" Transwell-like devices. However, microfluidic techniques have not achieved widespread usage in bioscience laboratories because they are not fully compatible with traditional, tried-and-true experimental protocols. To advance barrier tissue research, there is a need for a platform that combines the advantages of both conventional open-well and microfluidic systems. Here, we develop a plug-and-play flow module to add on-demand microfluidic capabilities to a modular microfluidic system featuring a silicon membrane "m-SiM" as an open-well device with live-cell imaging capabilities. The magnetic latching assembly of our design enables bi-directional reconfiguration between open-well and fluidic modes. This design feature allows users to conduct an experiment in an open-well format with established protocols and then add or remove microfluidic capabilities as desired. Our work also provides an experimentally-validated flow model to help select desired flow conditions based on the experimental needs. As a proof-of-concept, we demonstrate flow-induced alignment of endothelial cells and visualize different phases of neutrophil transmigration across an endothelial monolayer under flow. We anticipate that our reconfigurable design will be adopted by both engineering and bioscience laboratories due to the compatibility with standard open-well protocols and the simple flow addition capabilities.

bioengineering↗

bioRxiv2022

Local extensional flows promote long-range fiber alignment in 3D collagen hydrogels

Randomly oriented type I collagen (COL1) fibers in the extracellular matrix (ECM) are reorganized by biophysical forces into aligned domains extending several millimeters and with varying degrees of fiber alignment. These aligned fibers can transmit traction forces, guide tumor cell migration, facilitate angiogenesis, and influence tissue morphogenesis. To create aligned COL1 domains in microfluidic cell culture models, shear flows have been used to align thin COL1 matrices (<50m in height) in a microchannel. However, there has been limited investigation into the role of shear flows in aligning 3D hydrogels (>130m). Here, we show that pure shear flows do not induce fiber alignment in 3D atelo COL1 hydrogels, but the simple addition of local extensional flow promotes alignment that is maintained across several millimeters, with a degree of alignment directly related to the extensional strain rate. We further advance experimental capabilities by addressing the practical challenge of accessing a 3D hydrogel formed within a microchannel by introducing a magnetically coupled modular platform that can be released to expose the microengineered hydrogel. We demonstrate the platforms capability to pattern cells and fabricate multi-layered COL1 matrices using layer-by-layer fabrication and specialized modules. Our approach provides an easy-to-use fabrication method to achieve advanced hydrogel microengineering capabilities that combine fiber alignment with biofabrication capabilities.

bioengineering↗

bioRxiv2019

The effect of wrist posture on extrinsic finger muscle activity during single joint movements

Wrist posture impacts the muscle lengths and moment arms of the extrinsic finger muscles that cross the wrist. As a result, the electromyographic (EMG) activity associated with digit movement at different wrist postures may also change. Therefore, we sought to quantify the posture-dependence of extrinsic finger muscle activity. Fine-wire bipolar electrodes were inserted in the extrinsic hand muscles of able-bodied subjects to record EMG activity during wrist and finger movements in various postures. EMG activity of all the recorded finger muscles were significantly different (p<.05, ANOVA) when performing the same movement in five different wrist postures. EMG activity varied by up to 70%, with the highest levels of activity observed in finger extensors when the wrist was extended. Similarly, finger flexors were most active when the wrist was flexed. For the finger flexors, EMG variations with wrist posture were most prominent for index finger muscles, while the EMG activity of all finger extensor muscles were similarly modulated. The extrinsic finger muscles also showed significant activity during wrist movements with the digits held still regardless of finger posture, suggesting that they may play a role in generating torque during wrist movements. Finally, we developed a pair of generalized classifiers that show that finger muscle EMG can be used to predict wrist posture. These results may impact the design of biomimetic control algorithms for myoelectric prosthetic hands, but further work in transradial amputees is necessary to determine whether this phenomenon persists after amputation.

bioengineering↗