Biology subjects

Nelson, K. M.

Publications and source records attributed to Nelson, K. M..

5 recordsLinked to original sources

bioRxiv2025

A Microphysiologic Model of the Cervical Epithelium Recapitulates Microbial, Immunologic, and Pathogenic Properties of Sexually Transmitted Infections

Sexually transmitted infections (STIs) of the cervicovaginal mucosa are among the most common global infections. Clinical studies have revealed that susceptibility to STIs and the subsequent host responses they elicit are frequently associated with vaginal microbiota compositions that facilitate infection. Current monolayer cell culture and animal models fail to reproduce the multilevel complexity required to investigate these relationships simultaneously and/or with sufficient physiological relevance. To address this limitation, we have developed a microphysiologic system (MPS) that models human cervical tissue, its microbiota, and is susceptible to infection by two prominent genital pathogens, Chlamydia trachomatis and Neisseria gonorrhoeae. Significantly, this MPS platform recapitulates essential dynamic, polymicrobial, immune, and pathogenic features of chlamydial and gonococcal infections as they occur in humans. The lowcost MPS device requires no specialized equipment or specific expertise and was experimentally validated for both chlamydial and gonococcal infections across multiple nonengineering, remotely located laboratories, demonstrating its transferability and reproducibility. The MPS platform described herein provides a novel tool for expanded research into genital infections in a reconstituted system that closely mimics the cervical epithelium, a significant advance over existing models.

bioengineering↗

bioRxiv2025

Democratizing Organ-on-Chip Technologies with a Modular, Reusable, and Perfusion-Ready Microphysiological System

Organ-on-chip (OOC) technologies, also called microphysi-ological systems (MPS), offer dynamic microenvironments that improve upon static culture systems, yet widespread adoption has been hindered by fabrication complexity, reliance on poly-dimethylsiloxane (PDMS), and limited modularity. Here, we present a modular MPS platform designed for ease of use, re-producibility, and broad applicability. The system comprises layered elastomeric inserts for dual monolayer cell culture, which is clamped within a reusable acrylic cassette for perfusion studies. This enables researchers to decouple model establishment from flow experiments and streamline their work-flows. We validated the system using dual epithelial and en-dothelial cell co-culture under static and perfused conditions, including shear-induced alignment of HUVECs. Material testing confirmed biocompatibility, while vinyl cutting reproducibility demonstrated high manufacturing fidelity. The platform reliably supported long-term culture (up to 14 days), and the open insert format facilitated uniform seeding and imaging access. This approach enables parallelized experimentation, minimizes pump usage, and is well-suited for labs without microfabrication infrastructure. By combining fabrication flexibility with biological robustness, this work establishes a generalizable platform for modular tissue-chip development adapted to diverse organ systems and serves as a foundational framework for democratizing advanced in vitro model systems. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=159 SRC="FIGDIR/small/651503v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1e5fed3org.highwire.dtl.DTLVardef@bcf27eorg.highwire.dtl.DTLVardef@d46f33org.highwire.dtl.DTLVardef@d0912f_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

A straightforward cell culture insert model to incorporate biochemical and biophysical stromal properties into transplacental transport studies

IntroductionThe placental extracellular matrix (ECM) dynamically remodels over pregnancy and in disease. How these changes impact placental barrier function is poorly understood as there are limited in vitro models of the placenta with a modifiable stromal compartment to mechanistically investigate these extracellular factors. We developed a straightforward method to incorporate uniform hydrogels into standard cell culture inserts for transplacental transport studies. MethodsUniform polyacrylamide (PAA) gels were polymerized within cell culture inserts by (re)using the insert packaging to create a closed, controllable environmental chamber. PAA pre-polymer solution was added dropwise via a syringe to the cell culture insert and the atmosphere was purged with an inert gas. Transport and cell culture studies were conducted to validate the model. ResultsWe successfully incorporated and ECM functionalized uniform PAA gels to cell culture inserts enable cell adhesion and monolayer formation. Imaging and analyte transport studies validated gel formation and expected mass transport results and successful cell studies confirmed cell viability, monolayer formation, and that the model could be used transplacental transport studies. Detailed methods and validation protocols are included. DiscussionIt is well appreciated that ECM biophysical and biochemical properties impact cell phenotype and cell signaling in many tissues including the placenta. The incorporation of a PAA gel within a cell culture insert enables independent study of placental ECM biophysical and biochemical properties in the context of transplacental transport. These straightforward and low-cost methods to build three dimensional cellular models are readily adoptable by the wider scientific community.

physiology↗

bioRxiv2022

Lipid Nanoparticle Composition Drives Delivery of mRNA to the Placenta

Ionizable lipid nanoparticles (LNPs) have gained attention as mRNA delivery platforms for vaccination against COVID-19 and for protein replacement therapies. LNPs enhance mRNA stability, circulation time, cellular uptake, and preferential delivery to specific tissues compared to mRNA with no carrier platform. However, LNPs have yet to be developed for safe and effective mRNA delivery to the placenta as a method to treat placental dysfunction. Here, we develop LNPs that enable high levels of mRNA delivery to trophoblasts in vitro and to the placenta in vivo with no toxicity. We conducted a Design of Experiments to explore how LNP composition, including the type and molar ratio of each lipid component, drives trophoblast and placental delivery. Our data revealed that a specific combination of ionizable lipid and phospholipid in the LNP design yields high transfection efficiency in vitro. Further, we present one LNP platform that exhibits highest delivery of placental growth factor mRNA to the placenta in pregnant mice, which demonstrates induced protein synthesis and secretion of a therapeutic protein. Lastly, our high-performing LNPs have no toxicity to both the pregnant mice and fetuses. Our results demonstrate the feasibility of LNPs as a platform for mRNA delivery to the placenta. Our top LNPs may provide a therapeutic platform to treat diseases that originate from placental dysfunction during pregnancy.

bioengineering↗

bioRxiv2019

Virtual reality as a tool for environmental conservation and fundraising

Anecdotal evidence from philanthropic fundraisers shows that virtual reality (VR) technology increases empathy and can influence people toward pro-environmental behavior. Non-profit organizations are increasingly marketing their causes using virtual reality and they report increased donations when VR technology is employed. In VR, users are immersed in situations intended to feel more like the real world through technology, such as 360{degrees} video screened through 3D headsets that block out visual and auditory distractions. The framing of the message as either positive or negative has long shown to have an effect on behavior, although consensus on the impact of framing has not been reached in relation to encouraging contributions to public goods. This paper focuses on field experiments used to investigate the effects of varying degrees of visual immersion and positive versus negative message framing on respondents contributions to a conservation charity. Participants were exposed to a five-minute underwater film about coral reefs and the importance of protecting them. We employed a 2x2 experimental design using 3D head-mounted displays comparing 360{degrees} film footage vs. unidirectional film and a positive message vs. a negative message. After watching the film, each participant completed a short questionnaire and had the opportunity to donate to a marine conservation charity. In addition, we tested a control treatment where no video was observed. The video was filmed in Indonesia which is host to some of the worlds most biodiverse reefs that are under great threat from human activity. We also conducted the study in Indonesia, sampling a total of 1006 participants from the Bogor city area and tourists on the island of Gili Trawangan - which is popular for scuba diving and snorkeling. We find significant differences in observed behavior and reported emotions between all treatments compared to the control condition. Among the tourist sample, we find significant differences between the 360{degrees} film with a negative message which garnered significantly larger average donation amounts compared to the unidirectional film with both positive and negative framing. Overall, we can infer from these studies that virtual reality is an effective way to raise awareness of environmental threats and encourage behavioral action, especially when tailored to target groups. New technology, such as the VR head-mounted display, is highly effective at attracting interest which is an important point to encourage organizations to invest in new technologies.

scientific communication and education↗