ABSTRACT
Sprouting angiogenesis is a core biological process critical to vascular development. Its accurate simulation, relevant to multiple facets of human health, is of broad, interdisciplinary appeal. This study presents an in-silico model replicating a microfluidic assay where endothelial cells sprout into a biomimetic extracellular matrix, specifically, a large-pore, low-concentration fibrin-based porous hydrogel, influenced by chemotactic factors. We introduce a novel approach by incorporating the extracellular matrix and chemotactic factor effects into a unified term using a single parameter, primarily focusing on modelling sprouting dynamics and morphology. This continuous model naturally describes chemotactic-induced sprouting with no need for additional rules. In addition, we extended our base model to account for matrix sensing and degradation, crucial aspects of angiogenesis. We validate our model via a hybrid in-silico experimental method, comparing the model predictions with experimental results derived from the microfluidic setup. Our results underscore the intricate relationship between the extracellular matrix structure and angiogenic sprouting, proposing a promising method for predicting the influence of the extracellular matrix on angiogenesis.
ABSTRACT
The purpose of this work is to develop a hematocrit-independent method for the detection of beta-thalassemia trait (ß-TT) and iron deficiency anemia (IDA), through the rheological characterization of whole blood samples from different donors. The results obtained herein are the basis for the development of a front microrheometry point-of-care device for the diagnosis and clinical follow-up of ß-TT patients suffering hematological diseases and alterations in the morphology of the red blood cell (RBC). The viscosity is calculated as a function of the mean front velocity by detecting the sample fluid-air interface advancing through a microfluidic channel. Different viscosity curves are obtained for healthy donors, ß-TT and IDA samples. A mathematical model is introduced to compare samples of distinct hematocrit, classifying the viscosity curve patterns with respect to the health condition of blood. The viscosity of the fluid at certain shear rate values varies depending on several RBC factors such as shape and size, hemoglobin (Hb) content, membrane rigidity and hematocrit concentration. Blood and plasma from healthy donors are used as reference. To validate their potential clinical value as a diagnostic tool, the viscosity results are compared to those obtained by the gold-standard method for RBC deformability evaluation, the Laser-Optical Rotational Red Cell Analyzer (LoRRCA).
ABSTRACT
The motivation for this study was to develop a microdevice for the precise rheological characterization of biofluids, especially blood. The method presented was based on the principles of rheometry and fluid mechanics at the microscale. Traditional rheometers require a considerable amount of space, are expensive, and require a large volume of sample. A mathematical model was developed that, combined with a proper experimental model, allowed us to characterize the viscosity of Newtonian and non-Newtonian fluids at different shear rates. The technology presented here is the basis of a point-of-care device capable of describing the nonlinear rheology of biofluids by the fluid/air interface front velocity characterization through a microchannel. The proposed microrheometer uses a small amount of sample to deliver fast and accurate results, without needing a large laboratory space. Blood samples from healthy donors at distinct hematocrit percentages were the non-Newtonian fluid selected for the study. Water and plasma were employed as testing Newtonian fluids for validation of the system. The viscosity results obtained for the Newtonian and non-Newtonian fluids were consistent with pertinent studies cited in this paper. In addition, the results achieved using the proposed method allowed distinguishing between blood samples with different characteristics.
