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This paper provides a synopsis of discussions related to the Learning Environments track of the Fourth BME Education Summit held at Case Western Reserve University in Cleveland, Ohio in May 2019. This summit was organized by the Council of Chairs of Bioengineering and Biomedical Engineering, and participants included over 300 faculty members from 100+ accredited undergraduate programs. The Learning Environments track had six interactive workshops that provided facilitated discussion and provide recommendations in the areas of: (1) Authentic project/problem identification in clinical, industrial, and global settings, (2) Experiential problem/project-based learning within courses, (3) Experiential learning in co-curricular learning settings, (4) Team-based learning, (5) Teaching to reach a diverse classroom, and (6) innovative platforms and pedagogy. A summary of the findings, best practices and recommendations from each of the workshops is provided under separate headings below, and a list of resources is provided at the end of this paper.

We developed a two-dimensional model of transport-dependent intracellular calcium signaling in endothelial cells (ECs). Our purpose was to evaluate the effects of spatial colocalization of endothelial nitric oxide synthase (eNOS) and capacitative calcium entry (CCE) channels in caveolae on eNOS activation in response to ATP. Caveolae are specialized microdomains of the plasma membrane that contain a variety of signaling molecules to optimize their interactions and regulate their activity. In ECs, these molecules include CCE channels and eNOS. To achieve a quantitative understanding of the mechanisms of microdomain calcium signaling and the preferential sensitivity of eNOS to calcium entering the cell through CCE channels, we constructed a mathematical model incorporating the cell morphology and cellular physiological processes. The model predicts that the spatial segregation of calcium channels in ECs can create transport-dependent sharp gradients in calcium concentration within the cell. The calcium concentration gradient is affected by channel density and cell geometry. This transport-dependent calcium signaling specificity effect is enhanced in ECs by increasing the spatial segregation of the caveolar signaling domains. Our simulation significantly advances the understanding of how [Ca.sup.2+], despite its many potential actions, can mediate selective activation of signaling pathways. We show that diffusion-limited calcium transport allows functional compartmentalization of signaling pathways based on the spatial arrangements of [Ca.sup.2+] sources and targets. capacitative calcium entry; caveolae; endothelial cells: endothelial nitric oxide synthase; mathematical model

The drug-eluting stent's increasingly frequent occurrence late stage thrombosis have created a need for new strategies for intervention in coronary artery disease. This paper demonstrates further development of our minimally invasive, targeted drug delivery system that uses induced magnetism to administer repeatable and patient specific dosages of therapeutic agents to specific sites in the human body. Our first aim is the use of magnetizable stents for the prevention and treatment of coronary restenosis; however, future applications include the targeting of tumors, vascular defects, and other localized pathologies. Future doses can be administered to the same site by intravenous injection. This implant-based drug delivery system functions by placement of a weakly magnetizable stent or implant at precise locations in the cardiovascular system, followed by the delivery of magnetically susceptible drug carriers. The stents are capable of applying high local magnetic field gradients within the body, while only exposing the body to a modest external field. The local gradients created within the blood vessel create the forces needed to attract and hold drug-containing magnetic nanoparticles at the implant site. Once these particles are captured, they are capable of delivering therapeutic agents such as antineoplastics, radioactivity, or biological cells. Index Terms--Magnetic drug delivery, magnetic separation cardiovascular disease, stents.

A method is described for the manufacture of a microelectrode array for chronic, multichannel, single neuron recording. The ceramic-based, multisite electrode array has four recording sites patterned onto a ceramic shaft the size of a single typical microwire electrode. The sites and connecting wires are applied to the ceramic substrate using a reverse photolithographic procedure. Recording sites (22 x 80 [micro]m) are separated by 200 (micro)m along the shaft. A layer of alumina insulation is applied over the whole array (exclusive of recording sites) by ion-beam assisted deposition. These arrays were capable of recording single neuron activity from each of their recording sites for at least three weeks during chronic implantation in the somatosensory cortex of rats, and several sites had recordings that lasted for more than 8 weeks. The vertical arrangement of the recording sites on these electrodes is ideal for simultaneously recording across the different layers of brain areas such as the cerebral cortex and hippocampus in chronic preparations. Index Terms--Chronic implant, cortical histology, microelectrode array, multiple-single neuron recording, neural recording.

Determination of the distribution of shear stress on the flow-aligned and nonaligned endothelial surface due to shear flow using computational fluid dynamics combined with atomic force microscopy gives a complete description of the spatial distribution of stresses on endothelial monolayers. Endothelial shows an adaptive behavior in response to steady mechanical stimulation. The alignment of endothelial cells in response to flow gives evidence of mechanotransduction in endothelium.

The capability to deliver high effective dosages to specific sites in the human body has become the holy grail of drug delivery research. Drugs with proven effectiveness under in vitro investigation often reach a major roadblock under in vivo testing due to a lack of an effective delivery strategy. In addition, many clinical scenarios require delivery of agents that are therapeutic at the desired delivery point, but otherwise systemically toxic. We propose a method for targeted drug delivery by applying uniform magnetic fields to an injected superparamagnetic colloidal fluid carrying a drug. The experimental and theoretical models presented give insight into the use of magnetic microspheres for site-specific delivery of therapeutic agents and blood flow occlusion for embolotherapy. Index Terms--Embolotherapy, magnetic particles, magnetic targeting, targeted drug delivery.

The response of endothelial cells (ECs) to their hemodynamic environment strongly influences normal vascular physiology and the pathogenesis of atherosclerosis. Unique responses to the complex flow patterns in lesion-prone regions imply that the temporal and spatial features of the mechanical stimuli modulate the cellular response to flow. We report the first systematic study of the effects of temporal gradients of shear stress on ECs. Flow was applied to cultured ECs using a novel cone-and-plate device allowing precise and independent control of the shear stress magnitude and the onset rate. Intracellular free calcium concentration ([[[Ca.sup.2+]].sub.i]) increased rapidly following the onset of flow, and the characteristics of the transient were modulated by both the shear stress magnitude and onset rate. ECs were most sensitive to shear stress applied at physiological onset rates. Furthermore, the relative contribution of extracellular calcium and [IP.sub.3]-mediated release were dependent upon the ,specific flow regime. [S0148-0731(00)01003-7]