Evaluation of the effect of 3D porous Chitosan-alginate scaffold stiffness on breast cancer proliferation and migration.

Breast cancer (BCa) is one of the most common cancers for women and metastatic BCa causes the majority of deaths. The extracellular matrix (ECM) stiffens during cancer progression and provides biophysical signals to modulate proliferation, morphology, and metastasis. Cells utilize mechanotransduction and integrins to sense and respond to ECM stiffness. Chitosan-alginate (CA) scaffolds have been used for 3D culture, but lack integrin binding ligands, resulting in round cell morphology and limited cell-material interaction. In this study, 2, 4, and 6 wt% CA scaffolds were produced to mimic the stages of BCa progression and evaluate the BCa response to CA scaffold stiffness. All three CA scaffold compositions highly porous with interconnected pores and scaffold stiffness increased with increasing polymer concentration. MDA-MB-231 (231) cells were cultured in CA scaffolds and 2D cultures for 7 d. All CA scaffold cultures had similar cell numbers at 7 d and the 231 cells formed clusters that increased in size during the culture. The 2 wt% CA had the largest clusters throughout the 7 d culture compared with the 4 and 6 wt% CA. The 231 cell migration was evaluated on 2D surfaces after 7 d culture. The 6 wt% CA cultured cells had the greatest migration speed, followed by 4 wt% CA, 2D cultures, and 2 wt% CA. These results suggest that 231 cells sensed the stiffness of CA scaffolds without the presence of focal adhesions. This indicates that a non-integrin-based mechanism may explain the observed mechanotransduction response.

Lab-on-a-Chip for Cardiovascular Physiology and Pathology.

Lab-on-a-chip technologies have allowed researchers to acquire a flexible, yet relatively inexpensive testbed to study one of the leading causes of death worldwide, cardiovascular disease. Cardiovascular diseases, such as peripheral artery disease, arteriosclerosis, and aortic stenosis, for example, have all been studied by lab-on-a-chip technologies. These technologies allow for the integration of mammalian cells into functional structures that mimic vital organs with geometries comparable to those found in vivo. For this review, we focus on microdevices that have been developed to study cardiovascular physiology and pathology. With these technologies, researchers can better understand the electrical-biomechanical properties unique to cardiomyocytes and better stimulate and understand the influence of blood flow on the human vasculature. Such studies have helped increase our understanding of many cardiovascular diseases in general; as such, we present here a review of the current state of the field and potential for the future.

Bio-Inspired Microdevices that Mimic the Human Vasculature.

Blood vessels may be found throughout the entire body and their importance to human life is undeniable. This is evident in the fact that a malfunctioning blood vessel can result in mild symptoms such as shortness of breath or chest pain to more severe symptoms such as a heart attack or stroke, to even death in the severest of cases. Furthermore, there are a host of pathologies that have been linked to the human vasculature. As a result many researchers have attempted to unlock the mysteries of the vasculature by performing studies that duplicate the physiological structural, chemical, and mechanical properties known to exist. While the ideal study would consist of utilizing living, blood vessels derived from human tissue, such studies are not always possible since intact human blood vessels are not readily accessible and there are immense technical difficulties associated with such studies. These limitations have opened the door for the development of microdevices modeled after the human vasculature as it is believed by many researchers in the field that such devices can one day replace tissue models. In this review we present an overview of microdevices developed to mimic various types of vasculature found throughout the human body. Although the human body contains a diverse array of vascular systems for this review we limit our discussion to the cardiovascular system and cerebrovascular system and discuss such systems that have been fabricated in both 2D and 3D configurations.