Biology subjects

DeSimone, J. M.

Publications and source records attributed to DeSimone, J. M..

5 recordsLinked to original sources

bioRxiv2026

Rapid simulation of organ-scale oxygen transport for tissue ischemia prediction

A densely vascularized tissue can still be starved of oxygen. Tissue oxygenation depends heavily on vessel arrangement, blood flow distributions, and cellular metabolism. Resolving these effects from individual constituent vessels to whole organs has historically been computationally prohibitive. We introduce the Cardiovascular Analysis and Simulation of Circulatory Advection, Diffusion, and Exchange (CASCADE) toolkit, which makes vessel-resolved oxygen transport tractable at the organ scale through a novel screened Green's-function formulation. On laptop-class hardware, CASCADE simulates networks containing thousands of vessels in under one second and a full biventricular human heart model in about two minutes. We validate spatial oxygen and cell-survival predictions against experiments in perfused engineered tissues and matched finite-element simulations. In engineered tissues, sweeps across thousands of network designs and physiological conditions reveal when vessel density, oxygen supply, or network architecture limits viability, establishing design rules for sustaining thick constructs. In a human heart model, CASCADE translates coronary occlusion, anemia, polycythemia, and hypoxemia into distinct myocardial oxygenation patterns, revealing where oxygen delivery fails and how much tissue is at risk.

bioengineering↗

bioRxiv2026

Direct electrochemical cortisol detection via transition-resolved interrogation at a defect-engineered graphene interface

Continuous tracking of cortisol is central to understanding human stress physiology, yet direct electrochemical detection without biological receptors remains challenging despite its promise for stable and dynamic sensing. Electrochemical reduction of cortisol typically occurs at highly negative potentials, where parasitic interfacial currents, hydrogen evolution, and substantial capacitive background overlap with the cortisol reduction signal, preventing accurate quantification. We overcome this barrier through an integrated material-measurement strategy combining a defect-engineered graphene interface with a transition-resolved interrogation (TRI) measurement strategy. First, we engineered polybenzimidazole-derived laser-induced graphene containing nitrogen-rich defects while suppressing oxygen-derived functionalities which reduced parasitic background currents within the same cathodic potential regime. Next, we designed TRI to leverage differences in the time-dependent evolution of overlapping cathodic processes to isolate a localized cortisol-associated electrochemical reduction transition. Derivative-domain projection coupled with background estimation enables its reliable quantification. This integrated sensing architecture enables sensitive, selective, and dynamic cortisol detection in both artificial and biological interstitial fluids at low nanomolar concentrations. The response remains reproducible across physiologically relevant variations in pH, ionic strength, temperature, and repeated cycling. Together, these capabilities provide a basis for continuous electrochemical cortisol monitoring for future study of stress physiology.

bioengineering↗

bioRxiv2026

Photopatterned Sacrificial Vascular Architectures for Large Tissue-Scale Oxygenation

The engineering of thick, metabolically active tissues is constrained by the lack of scalable methods to create perfusable vasculature. This hinders effective metabolite transport in large tissue volumes, posing a critical barrier for regenerative tissue applications. In this study, we introduce photopatterned Channel Architectures with Sacrificial Templates (pCAST), an additive manufacturing strategy for generating three dimensional (3D), interconnected vascular networks with precisely defined negative space. Water-soluble sacrificial templates were fabricated using scalable Continuous Liquid Interface Production (CLIP), embedded within tissue constructs, and flushed away to yield 50 {micro}m perfusable channels spanning centimeter-scale tissue constructs. We then apply experimental oxygen mapping and viability analysis to pCAST constructs to build finite-element models that predict patterns of oxygen availability and tissue survival are governed by the balance between metabolic demand and vascular architecture, consistent with reaction-diffusion theory. This computational framework quantitatively predicts oxygen distributions and viability boundaries across vascular geometries and is validated experimentally. Together, these results establish pCAST as a scalable design framework linking vascular architecture, perfusion, and metabolic support for engineering large, 3D perfused tissue constructs. SignificanceThe ability to engineer thick, living tissues is limited by poor oxygen and nutrient delivery, which causes cell death before tissues can function or integrate with the body. This work addresses that fundamental barrier by introducing photopatterned Channel Architecture with Sacrificial Templates (pCAST), a scalable manufacturing strategy that creates precisely defined, perfusable vascular networks inside 3D tissues. By combining high-resolution 3D printing, sacrificial templating, and quantitative oxygen mapping, this research establishes design rules that link vascular geometry, perfusion, and tissue viability. These insights provide a general framework for building large, metabolically active tissues, with direct relevance to cardiac patches and other regenerative medicine applications.

bioengineering↗

bioRxiv2025

A Microneedle Device for Rapid Dermal Interstitial Fluid Sampling

Dermal interstitial fluid (ISF) offers a promising alternative to invasive blood tests and opportunities for novel skin diagnostics. Progress in both the understanding and adoption of ISF tests is hindered by sampling challenges, including lengthy collection times, non-negligible failure rates, variable collection volumes, and inconsistent bioanalyte levels. The causes of many of these issues are not well understood. We demonstrate a microneedle device that is several times faster than state-of-the-art, collecting an average of 15.5 mg of ISF in 5 minutes in humans with near-zero failure rate. This improvement was achieved by designing the spatial pressure gradient driving ISF flow. The influence of penetration depth, collection time, pressure, and age on ISF collection was elucidated, with Darcys law explaining multiple observations. A data-driven acceptance criterion of <1% blood contamination for ISF is proposed. The device and findings presented will empower researchers to better conduct robust studies in the development of ISF diagnostics.

bioengineering↗

bioRxiv2025

Free-Form Microfluidic Microneedle Array Patches

Personalized biomedical devices, such as microneedle array patches (MAPs), offer a promising transdermal drug delivery technology, providing a safe, painless, and self- administered alternative to traditional hypodermic injections. Despite their potential for precise therapeutic release, MAP adoption has been limited by challenges in payload capacity, treatment versatility, and manufacturing scalability. To address these issues, we integrated microfluidic channel designs with MAP technology, enhancing its functionality for delivering a range of payloads, from liquid therapeutics to solid-state cargos, at tunable volumes. Using injection continuous liquid interface production (iCLIP), a novel additive manufacturing approach, we fabricated high-resolution microfluidic MAPs with complex designs. Inspired by the stingers and fangs of various venomous animals, we developed a biomimetic microneedle design that prevents clogging, enhances mechanical strength, and eliminates needle leakage, thereby improving therapeutic delivery efficiency. Our technology reliably delivers multiple distinct payloads, enables combinational mixing, and enables point-of-care reconstitution of solid-state payloads. TeaserLeveraging biomimetic design and advanced 3D printing, we developed high-resolution microfluidic microneedle array patches (MAPs) that overcome payload and scalability challenges, offering a versatile and efficient platform for precise transdermal drug delivery.

bioengineering↗