Biology subjects

Veres, T.

Publications and source records attributed to Veres, T..

6 recordsLinked to original sources

bioRxiv2025

Conformal Bioprinting of Bi-phasic Jammed Bioinks, Independent of Gravity, Orientation, and Curvature

Rapid in situ bioprinting on complex, human-scale anatomical surfaces remain a key challenge for clinical translation. Here, we present a gravity-independent, conformal bioprinting strategy using bi-phasic granular bioink and multinozzle printheads capable of adapting to arbitrary surface curvatures. The bioink comprised of jammed gelatin microgels suspended in a fibrinogen matrix exhibits yield-stress behavior to maintain shape fidelity after extrusion while supporting cell viability and proliferation. Two monolithic multinozzle printhead architectures with identical bioink delivery networks were evaluated: (1) a rigid configuration for handheld bioprinting and (2) a soft robotic variant capable of real-time curvature adaptation via pneumatic actuation. Microgravity experiments aboard a parabolic flight confirmed successful bioink deposition under [~]0 g conditions. A ladder-rung microfluidic architecture ensured uniform bioink delivery across printhead nozzles, improving deposition consistency. In situ bioprinting on anatomical facial phantoms confirmed conformal, high-throughput (deposition at 20 mm{middle dot}s-1) deposition of bioink over physiologically relevant curvatures, both with and without cells. Cell-laden constructs retained >85% cell viability post-printing and supported proliferation. This work introduces a scalable bioprinting platform suitable for clinical, remote, and deep-space environments, enabling autonomous tissue fabrication. The curvature-adaptive printhead advances current in situ bioprinting capabilities, facilitating the generation of personalized grafts with complex anatomical geometries.

bioengineering↗

bioRxiv2025

PiP-plex: A Particle-in-Particle System for Multiplexed Quantification of Secreted Proteins by Single Cells

Cell signaling is modulated by the secretion of various proteins, which can be used to infer a cells phenotype. However, these proteins cannot be readily detected in multiplex by commonly used methods at the single cell level. Here, we present PiP-plex, a particles-in-particle (PiPs) system comprising (i) fluorescence intensity barcoded microparticles (BMPs) co-entrapped with (ii) a single cell inside an alginate hydrogel particle for multiplex protein secretion analysis by confocal microscopy. We show that developed PiPs maintained >90 % cellular viability and allowed live cells retrieval. A seven-plex fluorescent barcoding and concomitant sandwich immunoassay in PiPs were implemented with limits of detection ranging from 0.8 pg mL-1 to 2 ng mL-1 depending on the protein. PiP-plex assays were benchmarked with bulk immunoassays and found to rival or outperform them. We applied PiP-plex to analyze protein secreted by THP-1 cells upon exposure to lipopolysaccharide and detected varying cell responses, with a significant increase in MIP-1, TNF- and IL-17A. Multivariate analysis revealed that the majority of stimulated cells secreted either MIP-1 or IL-17A, while other cytokines were typically co-secreted. Using PiP-plex, we analyzed [~]750 THP-1 cells, showcasing its potential for characterizing cells and cell-based therapeutics for cancer immunotherapies.

bioengineering↗

bioRxiv2024

Tissue clocks derived from histological signatures of biological aging enable tissue-specific aging predictions from blood

Aging, the leading risk factor for numerous diseases, manifests through diverse structural and architectural changes in human tissues, providing an opportunity to quantify and interpret tissue-specific aging. To address this, we present a comprehensive assessment of tissue changes occurring during human aging, utilizing a vast array of whole slide histopathological images from the Genotype-Tissue Expression Project (GTEx), primarily reflecting non-diseased tissue samples. Using deep learning, we analyzed 25,712 images from 40 distinct tissue types across 983 individuals, quantifying nuanced morphological changes that tissues undergo with age. We developed tissue clocks--predictors of biological age based on tissue images--which achieved a mean prediction error of 4.9 years. These clocks were associated with established aging markers, including telomere attrition, subclinical pathologies, and comorbidities. In a systematic assessment of biological age rates across organs, we identified pervasive non-uniform rates of aging across the human lifespan, with some organs exhibiting earlier changes (20-40 years old) and others showing bimodal patterns of age-related changes. We also uncovered several associations between demographic, lifestyle, and medical history factors and tissue-specific acceleration or deceleration of biological age, highlighting potential modifiable risk factors that influenced the aging process at the tissue level. Finally, by combining paired histological images and gene expression data, we developed a strategy to predict tissue-specific age gaps from blood samples. This approach was validated in independent cohorts covering eight diseases, ranging from acute conditions like stroke to chronic diseases such as cystic fibrosis and Alzheimers disease. It successfully recovered significant associations with disease-relevant organs and revealed patterns of systemic and tissue-specific aging that may reflect broader physiological changes in health and disease. This work offers a new perspective on the aging process by positioning tissue structure as an integrator of cellular and molecular changes that reflect the physiological state of organs in health and disease. It underscores the value of histopathological imaging as a tool for understanding human aging and provides a foundation for the monitoring of tissue-specific aging processes in age-associated diseases.

physiology↗

bioRxiv2024

Biomimetic fractal topography enhances podocyte maturation in vitro

Cells and tissues in their native environment are organized into intricate fractal structures, which are rarely recapitulated in their culture in vitro. The extent to which fractal patterns that resemble complex topography in vivo influence cell maturation, and the cellular responses to such shape stimulation remain inadequately elucidated. Yet, the application of fractal cues (topographical stimulation via self-similar patterns) as an external input may offer a much-needed solution to the challenge of improving the differentiated cell phenotype in vitro. Here, we established fractality in podocytes, branching highly differentiated kidney cells, and glomerulus structure. Biomimetic fractal patterns derived from glomerular histology were used to generate topographical (2.5-D) substrates for cell culture. Podocytes grown on fractal topography were found to express higher levels of functional markers and exhibit enhanced cell polarity. To track morphological complexities of differentiated podocytes, we employed a fluorescent labelling assay where labelled individual cells are tracked within otherwise optically silent confluent cell monolayer to reveal cell-cell interdigitation. RNAseq analysis suggests enhanced ECM deposition and remodeling in podocytes grown on fractal topography compared to flat surface or non-fractal microcurvature, mediated by YAP signaling. The incorporation of fractal topography into standard tissue culture well plates as demonstrated here may serve as a user-friendly bioengineered platform for high-fidelity cell culture.

bioengineering↗

bioRxiv2023

Collagen Tubular Airway-on-Chip for Extended Epithelial Culture andInvestigation of Ventilation Dynamics

The lower respiratory tract is a hierarchical network of compliant tubular structures that are made from extracellular matrix proteins with a wall lined by an epithelium. While microfluidic airway-on-a-chip models incorporate the effects of shear and stretch on the epithelium, week-long air-liquid-interface (ALI) culture remains limited to static conditions. The circular cross-section and substrate compliance associated with intact airways have yet to be recapitulated to allow studies of epithelial injuries under physiological and ventilation conditions. To overcome these limitations, we present a collagen tube-based airway model. Sustaining a functional human bronchial epithelium during two-week perfusion is accomplished by continuously supplying warm, humid air at the apical side and culture medium at the basal side. The model faithfully recapitulates human airways in size, composition, and mechanical microenvironment, allowing for the first time dynamic studies of elastocapillary phenomena associated with regular breathing as well as mechanical ventilation, along with the impact on epithelial cells. Findings reveal the epithelium to become increasingly damaged when subjected to repetitive collapse and reopening as opposed to overdistension and suggest expiratory flow resistance to reduce atelectasis. We expect the model to find broad potential applications in organ-on-a-chip applications for various tubular tissues.

bioengineering↗

bioRxiv2019

Gravity-based microfiltration reveals unexpected prevalence of circulating tumor cell clusters in ovarian cancer

Circulating tumor cells (CTCs) are rare (few cells per milliliter of blood) and mostly isolated as single cell CTCs (scCTCs). CTC clusters (cCTCs), even rarer, are of growing interest, notably because of their higher metastatic potential, but very difficult to isolate. Here, we introduce gravity-based microfiltration (G{micro}F) for facile isolation of cCTCs while minimizing unwanted cluster disaggregation, with [~]85% capture efficiency. G{micro}F from orthotopic ovarian cancer mouse models, from 17 epithelial ovarian cancer (EOC) with either localized or metastatic disease, and from 13 metastatic colorectal cancer liver metastasis (CRCLM) patients uncovered cCTCs in every case, with between 2-100+ cells. cCTCs represented between 5-30% of all CTC capture events, and 10-80% of CTCs were clustered; remarkably, in 10 patients, most CTCs were circulating not as scCTCs, but as cCTCs. G{micro}F uncovered the unexpected prevalence and frequency of cCTCs including sometimes very large ones in EOC patients, and motivates additional studies to uncover their properties and role in disease progression.

bioengineering↗