2010
Author:
Publisher: Stanford University
ISBN:
Category :
Languages : en
Pages :
Get Book
Book Description
This dissertation investigated the role of biomechanics in two physiological systems, the heart and bone. Biomechanics motivates the study and characterization of how cells sense external forces and convert these signals into an intracellular response in a process called mechanotransduction. Three independent studies were designed with the goal of applying mechanical forces that mimic the in vivo microenvironment of either the heart or bone. The aim of these studies was to better under the mechanisms driving cellular processes, including cardiac myocyte differentiation and osteoblast mechanotransduction. The first study presents the design and implementation of tissue engineering approach to stem cell-based myocardial therapy. Three dimensional engineered heart tissue was formed by suspending human embryonic stem cell-derived cardiac myocytes isolated from beating embryoid bodies in a soluble extracellular matrix, and an in vitro mechanical conditioning regimen was applied at physiological levels of myocardial strain. The viability of the engineered stem cell tissue was monitored in vitro and in vivo for up to 8 weeks using molecular imaging of reporter gene activity. The application of cyclic mechanical strain in vitro resulted in cellular alignment along the axis of strain and an elongated cellular morphology with a high nuclear to cytoplasmic ratio, typical of neonatal cardiac myocytes, as well as increased expression of cardiac troponin I, in comparison to static controls. Analysis of the in vitro and in vivo bioluminescence imaging data demonstrated the viability of engineered heart tissue constructs; however, histology results showed immature cells within the implanted constructs, suggesting an inability of the stem cell-derived cardiac precursors to maintain a cardiac phenotype in vivo, as well the inherent inefficiency of the beating embryoid body method to identify and isolate cardiac myocyte precursors. The functional shortcomings exhibited by the embryoid body-based differentiation of embryonic stem cell-derived cardiac myocytes in the first study motivated further refinement of cardiac myocyte differentiation techniques. Therefore, the second study executed the design and fabrication of a microelectromechanical platform to study the role of electrical and mechanical stimulation in cardiac myocyte differentiation. The fabrication process used a combination of soft lithography and traditional microfabrication techniques to pattern thin film metal electrodes on an elastomeric polymer membrane. The completed device enabled coupled characterization and imaging of cardiac myocytes precursors, and the ability to assess the range of mechanical forces, up to 10% equibiaxial strain, that may induce or maintain a cardiac fate. Electrical continuity was demonstrated under static conditions but not under strain, and improvements in metal deposition and adhesion could address this performance defect. Beating clusters containing human embryonic stem cell-derived cardiac myocytes were plated on fabricated membranes, uncoated and coated with Matrigel, and cell viability was monitored using contrast microscopy. The third study transitioned to a different mechanical model of physiological forces, which was the application of oscillatory fluid flow-mediated fluid shear stress generated by the loading and unloading of bone. Specifically, the role of focal adhesion kinase, a protein tyrosine kinase recruited at focal adhesions and a major mediator of integrin signaling pathways, was studied in osteoblast mechanotransduction. The biochemical and transcriptional response of focal adhesion kinase mutant osteoblasts to physiological levels of shear stress induced by oscillatory fluid flow was impaired as measured by prostaglandin E2 release and cyclooxygenase-2 gene expression. Restoration of focal adhesion kinase expression with site-specific mutations at two tyrosine phosphorylation sites demonstrated that phosphorylation events play a
Author:
Publisher: Stanford University
ISBN:
Category :
Languages : en
Pages :
View
Book Description
This dissertation investigated the role of biomechanics in two physiological systems, the heart and bone. Biomechanics motivates the study and characterization of how cells sense external forces and convert these signals into an intracellular response in a process called mechanotransduction. Three independent studies were designed with the goal of applying mechanical forces that mimic the in vivo microenvironment of either the heart or bone. The aim of these studies was to better under the mechanisms driving cellular processes, including cardiac myocyte differentiation and osteoblast mechanotransduction. The first study presents the design and implementation of tissue engineering approach to stem cell-based myocardial therapy. Three dimensional engineered heart tissue was formed by suspending human embryonic stem cell-derived cardiac myocytes isolated from beating embryoid bodies in a soluble extracellular matrix, and an in vitro mechanical conditioning regimen was applied at physiological levels of myocardial strain. The viability of the engineered stem cell tissue was monitored in vitro and in vivo for up to 8 weeks using molecular imaging of reporter gene activity. The application of cyclic mechanical strain in vitro resulted in cellular alignment along the axis of strain and an elongated cellular morphology with a high nuclear to cytoplasmic ratio, typical of neonatal cardiac myocytes, as well as increased expression of cardiac troponin I, in comparison to static controls. Analysis of the in vitro and in vivo bioluminescence imaging data demonstrated the viability of engineered heart tissue constructs; however, histology results showed immature cells within the implanted constructs, suggesting an inability of the stem cell-derived cardiac precursors to maintain a cardiac phenotype in vivo, as well the inherent inefficiency of the beating embryoid body method to identify and isolate cardiac myocyte precursors. The functional shortcomings exhibited by the embryoid body-based differentiation of embryonic stem cell-derived cardiac myocytes in the first study motivated further refinement of cardiac myocyte differentiation techniques. Therefore, the second study executed the design and fabrication of a microelectromechanical platform to study the role of electrical and mechanical stimulation in cardiac myocyte differentiation. The fabrication process used a combination of soft lithography and traditional microfabrication techniques to pattern thin film metal electrodes on an elastomeric polymer membrane. The completed device enabled coupled characterization and imaging of cardiac myocytes precursors, and the ability to assess the range of mechanical forces, up to 10% equibiaxial strain, that may induce or maintain a cardiac fate. Electrical continuity was demonstrated under static conditions but not under strain, and improvements in metal deposition and adhesion could address this performance defect. Beating clusters containing human embryonic stem cell-derived cardiac myocytes were plated on fabricated membranes, uncoated and coated with Matrigel, and cell viability was monitored using contrast microscopy. The third study transitioned to a different mechanical model of physiological forces, which was the application of oscillatory fluid flow-mediated fluid shear stress generated by the loading and unloading of bone. Specifically, the role of focal adhesion kinase, a protein tyrosine kinase recruited at focal adhesions and a major mediator of integrin signaling pathways, was studied in osteoblast mechanotransduction. The biochemical and transcriptional response of focal adhesion kinase mutant osteoblasts to physiological levels of shear stress induced by oscillatory fluid flow was impaired as measured by prostaglandin E2 release and cyclooxygenase-2 gene expression. Restoration of focal adhesion kinase expression with site-specific mutations at two tyrosine phosphorylation sites demonstrated that phosphorylation events play a
Author: Adam Wittek
Publisher: Springer Science & Business Media
ISBN: 1441996192
Category : Technology & Engineering
Languages : en
Pages : 155
View
Book Description
One of the greatest challenges for mechanists is to extend the success of computational mechanics to fields outside traditional engineering, in particular to biology, biomedical sciences, and medicine. The proposed workshop will provide an opportunity for computational biomechanics specialists to present and exchange opinions on the opportunities of applying their techniques to computer-integrated medicine. These are peer-reviewed proceedings of the workshop affiliated to a major international research conference (Medical Image Computing and Computer Assisted Intervention MICCAI 2010 in Beijing) dedicated to research in the field of medical image computing and computer assisted medical interventions. The list of subjects covered include: medical image analysis, image-guided surgery, surgical simulation, surgical intervention planning, disease prognosis and diagnostics, injury mechanism analysis, implant and prostheses design, medical robotics.
Author: Mohamed Hamdy Doweidar
Publisher: Academic Press
ISBN: 012816610X
Category : Science
Languages : en
Pages : 430
View
Book Description
Advances in Biomechanics and Tissue Regeneration covers a wide range of recent development and advances in the fields of biomechanics and tissue regeneration. It includes computational simulation, soft tissues, microfluidics, the cardiovascular system, experimental methods in biomechanics, mechanobiology and tissue regeneration. The state-of-the-art, theories and application are presented, making this book ideal for anyone who is deciding which direction to take their future research in this field. In addition, it is ideal for everyone who is exploring new fields or currently working on an interdisciplinary project in tissue biomechanics. Combines new trends in biomechanical modelling and tissue regeneration Offers a broad scope, covering the entire field of tissue biomechanics Contains perspectives from engineering, medicine and biology, thus giving a holistic view of the field
Author: Jennifer Tryggvi Blundo
Publisher:
ISBN:
Category :
Languages : en
Pages :
View
Book Description
This dissertation investigated the role of biomechanics in two physiological systems, the heart and bone. Biomechanics motivates the study and characterization of how cells sense external forces and convert these signals into an intracellular response in a process called mechanotransduction. Three independent studies were designed with the goal of applying mechanical forces that mimic the in vivo microenvironment of either the heart or bone. The aim of these studies was to better under the mechanisms driving cellular processes, including cardiac myocyte differentiation and osteoblast mechanotransduction. The first study presents the design and implementation of tissue engineering approach to stem cell-based myocardial therapy. Three dimensional engineered heart tissue was formed by suspending human embryonic stem cell-derived cardiac myocytes isolated from beating embryoid bodies in a soluble extracellular matrix, and an in vitro mechanical conditioning regimen was applied at physiological levels of myocardial strain. The viability of the engineered stem cell tissue was monitored in vitro and in vivo for up to 8 weeks using molecular imaging of reporter gene activity. The application of cyclic mechanical strain in vitro resulted in cellular alignment along the axis of strain and an elongated cellular morphology with a high nuclear to cytoplasmic ratio, typical of neonatal cardiac myocytes, as well as increased expression of cardiac troponin I, in comparison to static controls. Analysis of the in vitro and in vivo bioluminescence imaging data demonstrated the viability of engineered heart tissue constructs; however, histology results showed immature cells within the implanted constructs, suggesting an inability of the stem cell-derived cardiac precursors to maintain a cardiac phenotype in vivo, as well the inherent inefficiency of the beating embryoid body method to identify and isolate cardiac myocyte precursors. The functional shortcomings exhibited by the embryoid body-based differentiation of embryonic stem cell-derived cardiac myocytes in the first study motivated further refinement of cardiac myocyte differentiation techniques. Therefore, the second study executed the design and fabrication of a microelectromechanical platform to study the role of electrical and mechanical stimulation in cardiac myocyte differentiation. The fabrication process used a combination of soft lithography and traditional microfabrication techniques to pattern thin film metal electrodes on an elastomeric polymer membrane. The completed device enabled coupled characterization and imaging of cardiac myocytes precursors, and the ability to assess the range of mechanical forces, up to 10% equibiaxial strain, that may induce or maintain a cardiac fate. Electrical continuity was demonstrated under static conditions but not under strain, and improvements in metal deposition and adhesion could address this performance defect. Beating clusters containing human embryonic stem cell-derived cardiac myocytes were plated on fabricated membranes, uncoated and coated with Matrigel, and cell viability was monitored using contrast microscopy. The third study transitioned to a different mechanical model of physiological forces, which was the application of oscillatory fluid flow-mediated fluid shear stress generated by the loading and unloading of bone. Specifically, the role of focal adhesion kinase, a protein tyrosine kinase recruited at focal adhesions and a major mediator of integrin signaling pathways, was studied in osteoblast mechanotransduction. The biochemical and transcriptional response of focal adhesion kinase mutant osteoblasts to physiological levels of shear stress induced by oscillatory fluid flow was impaired as measured by prostaglandin E2 release and cyclooxygenase-2 gene expression. Restoration of focal adhesion kinase expression with site-specific mutations at two tyrosine phosphorylation sites demonstrated that phosphorylation events play a role in prostaglandin release following oscillatory fluid flow. In conclusion, the role of mechanical forces, including the effect of cyclic mechanical strain in human embryonic stem cell-derived cardiac myocyte tissue engineering and the fluid shear stress-induced response of focal adhesion kinase mutant osteoblasts, was successfully demonstrated and quantified in this dissertation.
Author: Miguel Cerrolaza
Publisher: Academic Press
ISBN: 0128117192
Category : Technology & Engineering
Languages : en
Pages : 454
View
Book Description
Numerical Methods and Advanced Simulation in Biomechanics and Biological Processes covers new and exciting modeling methods to help bioengineers tackle problems for which the Finite Element Method is not appropriate. The book covers a wide range of important subjects in the field of numerical methods applied to biomechanics, including bone biomechanics, tissue and cell mechanics, 3D printing, computer assisted surgery and fluid dynamics. Modeling strategies, technology and approaches are continuously evolving as the knowledge of biological processes increases. Both theory and applications are covered, making this an ideal book for researchers, students and R&D professionals. Provides non-conventional analysis methods for modeling Covers the Discrete Element Method (DEM), Particle Methods (PM), MessLess and MeshFree Methods (MLMF), Agent-Based Methods (ABM), Lattice-Boltzmann Methods (LBM) and Boundary Integral Methods (BIM) Includes contributions from several world renowned experts in their fields Compares pros and cons of each method to help you decide which method is most applicable to solving specific problems
Author: J. Kajzer
Publisher: Springer Science & Business Media
ISBN: 4431669671
Category : Technology & Engineering
Languages : en
Pages : 266
View
Book Description
Human biomechanics is an important research field in achieving safety, health, comfort, and a high quality of life in a world where the older generation soon will outnumber the younger generation. Recently there have been significant developments in this new field ofresearch, addressing such issues as injury prevention in various types of accidents, the causes of human bodily dysfunction, function recovery through medical care and training, and func tional reinforcement by sports. These issues are studied on the basis of the biomechanics of the cells, tissues, organs, and systems of the human body. To achieve the aim of providing support for better lives from the aspect of mechanical engineering, the Human Life Support Biomechanics Endowed Chair at the Graduate School of Engineering at Nagoya University was established more than 3 years ago with a donation from the Toyota Motor Corporation. Since that time, we have been conducting intensive research in the field as well as trying to publicize our work in Japan. The results of our research have been presented at conferences both at home and abroad. We have also en deavored to underscore the importance of the field by organizing symposiums with carefully designed programs.
Author: Y.C. Fung
Publisher: Springer Science & Business Media
ISBN: 1441968563
Category : Science
Languages : en
Pages : 570
View
Book Description
Biomechanics aims to explain the mechanics oflife and living. From molecules to organisms, everything must obey the laws of mechanics. Clarification of mechanics clarifies many things. Biomechanics helps us to appreciate life. It sensitizes us to observe nature. It is a tool for design and invention of devices to improve the quality of life. It is a useful tool, a simple tool, a valuable tool, an unavoidable tool. It is a necessary part of biology and engineering. The method of biomechanics is the method of engineering, which consists of observation, experimentation, theorization, validation, and application. To understand any object, we must know its geometry and materials of construc tion, the mechanical properties of the materials involved, the governing natural laws, the mathematical formulation of specific problems and their solutions, and the results of validation. Once understood, one goes on to develop applications. In my plan to present an outline of biomechanics, I followed the engineering approach and used three volumes. In the first volume, Biomechanics: Mechanical Properties of Living Tissues, the geometrical struc ture and the rheological properties of various materials, tissues, and organs are presented. In the second volume, Biodynamics: Circulation, the physiology of blood circulation is analyzed by the engineering method.
Author: Masao Tanaka
Publisher: Springer Science & Business Media
ISBN: 4431540725
Category : Technology & Engineering
Languages : en
Pages : 196
View
Book Description
Rapid developments have taken place in biological/biomedical measurement and imaging technologies as well as in computer analysis and information technologies. The increase in data obtained with such technologies invites the reader into a virtual world that represents realistic biological tissue or organ structures in digital form and allows for simulation and what is called “in silico medicine.” This volume is the third in a textbook series and covers both the basics of continuum mechanics of biosolids and biofluids and the theoretical core of computational methods for continuum mechanics analyses. Several biomechanics problems are provided for better understanding of computational modeling and analysis. Topics include the mechanics of solid and fluid bodies, fundamental characteristics of biosolids and biofluids, computational methods in biomechanics analysis/simulation, practical problems in orthopedic biomechanics, dental biomechanics, ophthalmic biomechanics, cardiovascular biomechanics, hemodynamics, cell mechanics, and model-, rule-, and image-based methods in computational biomechanics analysis and simulation. The book is an excellent resource for graduate school-level engineering students and young researchers in bioengineering and biomedicine.
Author: G. W. Schmid-Schönbein
Publisher: Springer Science & Business Media
ISBN: 1461248663
Category : Medical
Languages : en
Pages : 395
View
Book Description
Biomechanics is concerned with the response of living matter to forces, and its study has taken long strides in recent years. In the past two decades, biomechanics has brought improved understanding of normal and patho physiology of organisms at molecular, cellular, and organ levels; it has helped developing medical diagnostic and treatment procedures; it has guided the design and manufacturing of prosthesis and instruments; it has suggested the means for improving human performance in the workplace, sports, and space; it has made us understand trauma in war and in peace. Looking toward the future, we see many more areas of possible development such as: reduction in heart diseases and atherosclerosis improved vascular assist and replacement devices, including a permanent artifical heart enhanced oxygen transport in the lung understanding and control of growth and changes mechanics of neuromuscular control and robotics prevention of joint degeneration permanent total joint replacements prevention of low back pain workplace designs to enhance productivity ambulation systems for the handicapped fully implantable hearing aids improved understanding of the mechanisms for permanent disability injuries identification of factors such as alcohol use and disease influence on impact tolerance improved cellular bioreactor designs mechanics of DNA and its application in biotechnology. * Obviously, the attainment of these prospects will greatly improve the quality of human life and reduce the costs of living. * This list is from a report by the U. S. National Committee on Biomechanics, April, 1985.
Author: Jeff R. Crandall
Publisher: Springer Science & Business Media
ISBN: 1461441544
Category : Science
Languages : en
Pages : 342
View
Book Description
Pediatric Injury Biomechanics: Archive and Textbook consolidates and describes the current state of the art in pediatric injury biomechanics research in the automotive crash environment. Written by the most respected scientists in the field, the objective of this ground-breaking project is to provide a comprehensive archive and analysis of pediatric injury biomechanics research; to be the go-to reference for the epidemiology of motor vehicle related childhood injury data, pediatric anthropometry, pediatric biomechanical properties, tissue tolerance, and computational models. This book provides essential information needed by researchers working in the field of pediatric injury including those involved in rulemaking activities, injury criteria development, child dummy development, and child injury interventions development. In addition to the text, a companion archive will include valuable information and tools to assist in the identification of gaps in research and future research directions.This living document will be regularly updated with current research and advancements in pediatric injury biomechanics.
