Chemical Power for Microscopic Robots in Capillaries

The power available to microscopic robots (nanorobots) that oxidize bloodstream glucose while aggregated in circumferential rings on capillary walls is evaluated with a numerical model using axial symmetry and time-averaged release of oxygen from passing red blood cells. Robots about one micron in size can produce up to several tens of picowatts, in steady-state, if they fully use oxygen reaching their surface from the blood plasma. Robots with pumps and tanks for onboard oxygen storage could collect oxygen to support burst power demands two to three orders of magnitude larger. We evaluate effects of oxygen depletion and local heating on surrounding tissue. These results give the power constraints when robots rely entirely on ambient available oxygen and identify aspects of the robot design significantly affecting available power. More generally, our numerical model provides an approach to evaluating robot design choices for nanomedicine treatments in and near capillaries.Comment: 28 pages, 7 figure

Mechanical and Systems Biology of Cancer

Mechanics and biochemical signaling are both often deregulated in cancer, leading to cancer cell phenotypes that exhibit increased invasiveness, proliferation, and survival. The dynamics and interactions of cytoskeletal components control basic mechanical properties, such as cell tension, stiffness, and engagement with the extracellular environment, which can lead to extracellular matrix remodeling. Intracellular mechanics can alter signaling and transcription factors, impacting cell decision making. Additionally, signaling from soluble and mechanical factors in the extracellular environment, such as substrate stiffness and ligand density, can modulate cytoskeletal dynamics. Computational models closely integrated with experimental support, incorporating cancer-specific parameters, can provide quantitative assessments and serve as predictive tools toward dissecting the feedback between signaling and mechanics and across multiple scales and domains in tumor progression.Comment: 18 pages, 3 figure

THE EFFECT OF ARTERY BIFURCATION ANGLES ON FLUID FLOW AND WALL SHEAR STRESS IN THE MIDDLE CEREBRAL ARTERY

Saccular aneurysms are the abnormal plastic deformation of veins and arteries that can lead to lethal thrombus genesis or internal hemorrhaging. Medication and surgery greatly reduce the mortality rates, but treatment is limited by predicting who will develop aneurysms. A common location for saccular aneurysm genesis is at the main middle cerebral artery (MCA) bifurcation. The main MCA bifurcation is comprised of the M1 MCA segment, parent artery, and two M2 segments, daughter arteries. Studies have found that the lateral angle (LA) ratio of the MCA bifurcation is correlated with aneurysm formation. The LA ratio is defined as the angle between the M1 and the larger M2 divided by the angle between the M1 and the smaller M2. When the LA ratio is equal to 1, perfectly symmetrical, no aneurysms are found at the MCA bifurcation. When the LA ratio is greater than 1.6, aneurysms are commonly found at the MCA bifurcation. In the research described here, varying MCA bifurcation angles were compared to uncover any changes to fluid flow and wall shear stress that could stimulate aneurysm growth. Eight pre-aneurysm MCA bifurcation models were created in SolidWorks® using 120 degrees, 90 degrees, and 60 degrees as the angle between the M1 and the larger M2. LA ratios of 1, 1.6 and 2.2 were then used to characterize the other branch angle (60 degrees with a LA ratio of 1 was excluded). These models were imported into COMSOL Multiphysics® where the laminar fluid flow module was used to simulate non-Newtonian blood flow. Fluid flow profiles showed little to no change between the models. Shear stress changed when the LA ratio was increased, but the changed varied between the 120, 90 and 60 degree models. 120 degree models had a 3.87% decrease in max shear stress with a LA ratio of 2.2 while the 90 degree models had 7.5% decrease in max shear stress with a LA ratio of 2.2. Each daughter artery had distinct areas of high shear stress when the LA ratio equaled 1. Increasing the LA ratio or decreasing the bifurcation angle caused the areas of shear stress to merge together. Increasing LA ratio caused shear stress to decrease and spread around the MCA bifurcation. The reduction in max wall shear stress for high LA ratios supports current aneurysm genesis hypothesizes, but additional testing is required before bifurcation geometries can be used to predicted aneurysm genesis

A 3-Dimensional In Silico Test Bed for Radiofrequency Ablation Catheter Design Evaluation and Optimization

Atrial fibrillation (AF) is the disordered activation of the atrial myocardium, which is a major cause of stroke. Currently, the most effective, minimally traumatic treatment for AF is percutaneous catheter ablation to isolate arrhythmogenic areas from the rest of the atrium. The standard in vitro evaluation of ablation catheters through lesion studies is a resource intensive effort due to tissue variability and visual measurement methods, necessitating large sample sizes and multiple prototype builds. A computational test bed for ablation catheter evaluation was built in SolidWorks® using the morphology and dimensions of the left atrium adjacent structures. From this geometry, the physical model was built in COMSOL Multiphysics®, where a combination of the laminar fluid flow, electrical currents, and bioheat transfer was used to simulate radiofrequency (RF) tissue ablation. Simulations in simplified 3D geometries led to lesions sizes within the reported ranges from an in-vivo ablation study. However, though the ellipsoid lesion morphologies in the full atrial model were consistent with past lesion studies, perpendicularly oriented catheter tips were associated with decreases of -91.3% and -70.0% in lesion depth and maximum diameter. On the other hand, tangentially oriented catheter tips produced lesions that were only off by -28.4% and +7.9% for max depth and max diameter. Preliminary investigation into the causes of the discrepancy were performed for fluid velocities, contact area, and other factors. Finally, suggestions for further investigation are provided to aid in determining the root cause of the discrepancy, such that the test bed may be used for other ablation catheter evaluations

In silico bone mechanobiology: modeling a multifaceted biological system.

Mechanobiology, the study of the influence of mechanical loads on biological processes through signaling to cells, is fundamental to the inherent ability of bone tissue to adapt its structure in response to mechanical stimulation. The immense contribution of computational modeling to the nascent field of bone mechanobiology is indisputable, having aided in the interpretation of experimental findings and identified new avenues of inquiry. Indeed, advances in computational modeling have spurred the development of this field, shedding new light on problems ranging from the mechanical response to loading by individual cells to tissue differentiation during events such as fracture healing. To date, in silico bone mechanobiology has generally taken a reductive approach in attempting to answer discrete biological research questions, with research in the field broadly separated into two streams: (1) mechanoregulation algorithms for predicting mechanobiological changes to bone tissue and (2) models investigating cell mechanobiology. Future models will likely take advantage of advances in computational power and techniques, allowing multiscale and multiphysics modeling to tie the many separate but related biological responses to loading together as part of a larger systems biology approach to shed further light on bone mechanobiology. Finally, although the ever-increasing complexity of computational mechanobiology models will inevitably move the field toward patient-specific models in the clinic, the determination of the context in which they can be used safely for clinical purpose will still require an extensive combination of computational and experimental techniques applied to in vitro and in vivo applications. For further resources related to this article, please visit the WIREs website

미세 구조체와 aspiration 기반 세포 패터닝 기술을 통한 폐포 조직 환경 모사 개방형 구조 미세유체 플 랫폼의 개발

학위논문(석사) -- 서울대학교대학원 : 공과대학 기계공학과, 2022.2. 전누리.Engineering a thin air-liquid interface membrane is important to model in vitro the complex lung alveoli structure. To date, only few in vitro microfluidic platforms have been able to reproduce the in vivo size of alveoli while making it fast, easy to pattern and with a high yield. Moreover, no current platforms are including lung fibroblasts in the model. Here, we introduce a 3D printed open microfluidic and technique to create a thin hydrogel membrane close to the alveoli dimensions around a 100µm and usable for cell culture. 3D printed organ-on-chips allow the same biological performance and biodegradability in comparison to the usual PDMS chips while providing a high-throughput and no small molecule absorption. Utilizing the strong surface tension between hydrogel and closely spaced micropillars, after the suction of the liquid, provides a solution to pattern the desired thin hydrogel membrane. These platforms using specific patterning techniques can be used for a wide range of applications as an air-liquid interface model for powder inhalation tests or pharmaceutical drugs screening for instance.Abstract iii List of Tables 1 List of Figures 2 Chapter 1. Introduction 3 1.1. Study Background 3 1.2. Purpose of Research 5 Chapter 2. Materials and methods 7 2.1. Device fabrication 7 2.2. Cell preparation 8 2.3. Preparation and loading of the alveoli cell configuration 8 2.4. Immunostaining 10 2.5. Imaging 10 2.6. Numerical simulation 11 2.7. Statistical analysis 11 Chapter 3. Results and discussion 12 3.1. Capillary pinning liquid patterning process 13 3.1 Surface treatment 13 3.1.2. Numerical simulation 16 3.1.3. Theoretical analysis of the capillary pinning 17 3.2. Patterning for cells co culture in a 3D microenvironment 27 3.3. An open microfluidic platform to recreate the in vivo environment 30 Chapter 4. Conclusion 34 Bibliography 37석

The influence of mechanical stress on the growth and remodeling of a tumor

Mechanical forces are generated during tumor growth and progression. Numerous studies have investigated the effect of mechanical stress on cell behaviors, but there is still much to be understood. Many experimental and theoretical studies have investigatedthe effect of mechanical forces using multicellular tumor spheroids (MCTSs) as models of pre-vascular tumor growth. Here, we review two theoretical studies. In the first, “Influence of the mechanical properties of the necrotic core on the growth and remodeling of tumour spheroids,” Giverso and Preziosi (2019) [1] develop a mathematical model to study the growth and remodeling of a MCTSwith a necrotic core, which is composed of either calcified debris or a liquid cavity. In the second, “An avascular tumor growth model based on porous media mechanics and evolving natural states,” Mascheroniet al. (2018) [2] analyze the influence of the microenvironment on tumor growth and remodeling

Computational Modeling of Fluid Flow and Intra-Ocular Pressure following Glaucoma Surgery

Background Glaucoma surgery is the most effective means for lowering intraocular pressure by providing a new route for fluid to exit the eye. This new pathway is through the sclera of the eye into sub-conjunctival tissue, where a fluid filled bleb typically forms under the conjunctiva. The long-term success of the procedure relies on the capacity of the sub-conjunctival tissue to absorb the excess fluid presented to it, without generating excessive scar tissue during tissue remodeling that will shut-down fluid flow. The role of inflammatory factors that promote scarring are well researched yet little is known regarding the impact of physical forces on the healing response. Methodology To help elucidate the interplay of physical factors controlling the distribution and absorption of aqueous humor in sub-conjunctival tissue, and tissue remodeling, we have developed a computational model of fluid production in the eye and removal via the trabecular/uveoscleral pathways and the surgical pathway. This surgical pathway is then linked to a porous media computational model of a fluid bleb positioned within the sub-conjunctival tissue. The computational analysis is centered on typical functioning bleb geometry found in a human eye following glaucoma surgery. A parametric study is conducted of changes in fluid absorption by the sub-conjunctival blood vessels, changes in hydraulic conductivity due to scarring, and changes in bleb size and shape, and eye outflow facility. Conclusions This study is motivated by the fact that some blebs are known to have ‘successful’ characteristics that are generally described by clinicians as being low, diffuse and large without the formation of a distinct sub-conjunctival encapsulation. The model predictions are shown to accord with clinical observations in a number of key ways, specifically the variation of intra-ocular pressure with bleb size and shape and the correspondence between sites of predicted maximum interstitial fluid pressure and key features observed in blebs, which gives validity to the model described here. This model should contribute to a more complete explanation of the physical processes behind successful bleb characteristics and provide a new basis for clinically grading blebs

Asymmetry of tensile vs. compressive elasticity and permeability contributes to the regulation of exchanges in collagen gels

The Starling principle describes exchanges in tissues based on the balance of hydrostatic and osmotic flows. This balance neglects the coupling between mechanics and hydrodynamics, a questionable assumption in strained elastic tissues due to intravascular pressure. Here, we measure the elasticity and permeability of collagen gels under tensile and compressive stress via the comparison of the temporal evolution of pressure in an air cavity sealed at the outlet of a collagen slab with an analytical kinetic model. We observe a drop in the permeability and enhanced strain-stiffening of native collagen gels under compression, both effects being essentially lost after chemical cross-linking. Further, we prove that this asymmetric response accounts for the accumulation of compressive stress upon sinusoidal fluid injection, which modulates the material's permeability. Our results thus show that the properties of collagen gels regulate molecular exchanges and could help understand drug transport in tissues

Bio-Inspired design of a porous resorbable scaffold for bone reconstruction: a preliminary study

The study and imitation of the biological and mechanical systems present in nature and living beings always have been sources of inspiration for improving existent technologies and establishing new ones. Pursuing this line of thought, we consider an artificial graft typical in the bone reconstruction surgery with the same microstructure of the bone living tissue and examine the interaction between these two phases, namely bone and the graft material. Specifically, a visco-poroelastic second gradient model is adopted for the bone-graft composite system to describe it at a macroscopic level of observation. The second gradient formulation is employed to consider possibly size effects and as a macroscopic source of interstitial fluid flow, which is usually regarded as a key factor in bone remodeling. With the help of the proposed formulation and via a simple example, we show that the model can be used as a graft design tool. As a matter of fact, an optimization of the characteristics of the implant can be carried out by numerical investigations. In this paper, we observe that the size of the graft considerably influences the interaction between bone tissue and artificial bio-resorbable material and the possibility that the bone tissue might substitute more or less partially the foreign graft for better bone healing