Health

Blood is a life-saving resource in patient care. However, since blood banks depend entirely on donations, blood supply is often not enough. To prevent shortages, synthetic blood substitutes are explored.

In this work, we developed erythrocyte membrane-mimicking lipid coatings and applied them to oxygen-generating polycaprolactone microparticles (OG-PCL MPs) to test their potential as erythrocyte substitutes.

A solvent gradient-based lipid coating method was first developed in-house. Four synthetic lipid formulations were designed based on the lipid composition of the erythrocyte membrane and applied to different particle substrates. Hemolysis, coagulation time, and blood biomarker assays were conducted to determine the most hemocompatible formulation. Next, oxygen-generating microparticles were produced by incorporating calcium peroxide crystals (CPO) into PCL MPs (OG-PCL MPs). These constructs were then lipid-coated (OG-PCL-I MPs) and characterized in terms of particle structure and cytocompatibility.

Bio-inspired lipid formulations were successfully applied to a range of particle substrates used in nanomedicine. Complex lipid formulations resulted in overall better coating efficiency, higher particle stability, and an improved immune response in blood compared to minimal formulations. OG-PCL MPs revealed an ability to sustainably release O­₂ over time, and fluorescence microscopy confirmed lipid coating formation. Cytotoxicity assays suggest that both polymeric matrix and lipid coating improve the viability response of human umbilical vein endothelial cells (HUVECs) to oxygen-generating compounds.

We describe a novel, bio-inspired and self-oxygenating synthetic erythrocyte. Ongoing and following work will focus on the in vitro and in vivo circulatory safety of these constructs for application as engineered blood substitutes.

Current animal models are not reliable enough to predict the cardiac responses in humans and although human pluripotent stem cell (hPSC)-derived cardiomyocytes (hPSC-CMs) offer great promise, their immature fetal-like features represent a challenge for accurate disease modeling and drug testing. Therefore, there is an urgent need to use advanced human-based models for assessment of organ function. In vitro 3D cardiac models like engineered heart tissues (EHTs) have been shown to recapitulate tissue organization, function and cell-cell interactions of the adult human heart and they can be patient-specific. At the BIOS Lab on a Chip group in collaboration with the Department of Applied Stem Cell Technologies (AST), we have developed a modular and versatile platform designed to fit into a commercial 12-well plate with 3 technical replicates per well (a total of 36 EHTs per plate). We have used this advanced EHT platform that enables detailed analysis of hallmark physiological features of 3D cardiac tissues, to evaluate the effect of different drug compounds on the contractile performance of cardiac cells.

Optical coherence tomography (OCT) is a non-invasive, medical imaging modality that creates three-dimensional images of tissue, using an interferometer with a broadband source. As the light source in OCT spans multiple wavelengths, spectral analysis of the OCT signal (termed spectroscopic OCT, sOCT) can be employed to retrieve wavelength-dependent properties of tissue. sOCT systems using visible-light sources (vis-sOCT) benefit from shorter wavelengths and higher spectral contrast between the main tissue chromophores than those in the infrared. Vis-sOCT is particularly sensitive to the absorption by hemoglobin since it is more pronounced in the visible wavelength range. In this presentation, we explore the ability of vis-sOCT to quantify total hemoglobin concentrations [tHb] in-vivo and its capability for imaging neovascularization in organ-on-chip retina models and to track the thrombi formation in a blood vessel-on-chip model.

Not only the tumor itself but its micro-environment has a strong influence on cancer progression and therapy resistance. The bone marrow is the third most frequent site of metastasis and is considered a ‘safe haven’ for disseminated cancer cells. During first-line treatments, the environment of the bone marrow offers transient protection from the cytotoxic effects of chemotherapeutics. The small fraction of surviving tumor cells typically remains undetected, which provides the opportunity to develop permanent resistance mechanisms.

Mesenchymal stromal cells in the bone marrow (BM-MSCs) are increasingly recognized as important contributors to therapy resistance. Especially in the context of neuroblastoma – a childhood cancer arising from developing nerve cells – a detailed mechanistic understanding of their tumor-supportive communication is missing.

In my research, we aim to map the communication flow between BM-MSCs and neuroblastoma cells leading up to the acquisition of therapy resistance. To this end, secreted biological messages from the two cell types will be intercepted from in vitro co-cultures and identified by downstream analyses. I will explain how we combine metabolic labeling and click chemistry to introduce time- and cell-specificity to the ‘sea’ of biomolecules present in culture media. In addition, I will describe how understanding the communication flow can provide novel options for diagnosis, prognosis, and treatment of cancer.