Biomedical subjects

J D Humphrey

Publications and source records attributed to J D Humphrey.

At least 19 recordsLinked to original sources

PubMed2007

Stress-strain behavior of the passive basilar artery in normotension and hypertension.

Vascular cells are very responsive to even subtle changes in their local mechanical environment, thus there is a pressing need to quantify normal states of stress and strain as well as any perturbations from these normal states. Toward this end, we must quantify constitutive behaviors for both normal and adapted (maladapted) arteries. In this note, we report the first quantification of changes in the biaxial mechanical behavior of the passive basilar artery due to hypertension.

Basilar Artery↗

PubMed2007

Regional multiaxial mechanical properties of the porcine anterior lens capsule.

The lens capsule of the eye plays fundamental biomechanical roles in both normal physiological processes and clinical interventions. There has been modest attention given to the mechanical properties of this important membrane, however, and prior studies have focused on 1-D analyses of the data. We present results that suggest that the porcine anterior lens capsule has a complex, regionally dependent, nonlinear, anisotropic behavior. Specifically, using a subdomain inverse finite element method to analyze data collected via a new biplane video-based test system, we found that the lens capsule is nearly isotropic (in-plane) near the pole but progressively stiffer in the circumferential compared to the meridional direction as one approaches the equator. Because the porcine capsule is a good model of the young human capsule, there is strong motivation to determine if similar regional variations exist in the human lens capsule for knowledge of such complexities may allow us to improve the design of surgical procedures and implants.

Animals↗

PubMed2007

Altered multiaxial mechanical properties of the porcine anterior lens capsule cultured in high glucose.

Hyperglycemia can alter the mechanical properties of tissues through the formation of advanced glycation endproducts in matrix proteins that have long half-lives. We used a custom experimental system and subdomain finite element method to quantify alterations in the regional multiaxial mechanical properties of porcine lens capsules that were cultured for 8 or 14 weeks in high glucose versus control media. Findings revealed that high glucose significantly stiffened the capsules in both the circumferential and the meridional directions, but it did not affect the known regional variations in anisotropy. Such information could be important in the design of both improved clinical procedures and intraocular implants for diabetic patients.

Animals↗

PubMed2006

Biomechanics of the porcine basilar artery in hypertension.

Hypertension is a significant risk factor for diverse cerebrovascular diseases ranging from stroke to arteriovenous malformations and saccular aneurysms. Our increasing understanding of vascular mechanobiology reveals that changes in mechanical stimuli, such as increased blood pressure, alter basic cellular functions including the production and degradation of extracellular matrix as well as proliferation, migration, and apoptosis. Understanding changes in the biomechanical properties of the vascular wall is fundamental to correlating mechanobiological responses with the altered loads. In this paper, we present the first biomechanical data on a large cerebral artery in terms of the time of development of hypertension in maturity. Specifically, we report rapid changes in both the structural and the material stiffness of the passive basilar artery in a novel aortic-coarctation model of hypertension in the mini-pig. Histological measurements reveal associated increases in fibrillar collagens in the media and adventitia as well as increased smooth muscle in the media. That such dramatic changes occur within 2 weeks of the initiation of hypertension in maturity necessitates a detailed study of the early changes as well as the potential to reverse these changes at later times.

Animals↗

PubMed2006

A theoretical model of enlarging intracranial fusiform aneurysms.

The mechanisms by which intracranial aneurysms develop, enlarge, and rupture are unknown, and it remains difficult to collect the longitudinal patient-based information needed to improve our understanding. We submit, therefore, that mathematical models hold promise by allowing us to propose and test competing hypotheses on potential mechanisms of aneurysmal enlargement and to compare predicted outcomes with limited clinical information--in this way, we may begin to narrow the possible mechanisms and thereby focus experimental studies. In this paper, we present a constrained mixture model of evolving thin-walled, fusiform aneurysms and compare multiple competing hypotheses with regard to the production, removal, and alignment of the collagen that provides the structural integrity of the wall. The results show that this type of approach has the capability to infer potential means by which lesions enlarge and whether such changes are likely to produce a stable or unstable process. Such information can better direct the requisite histopathological examinations, particularly on the need to quantify collagen orientations as a function of lesion geometry.

Animals↗

PubMed2005

Histological evidence for the role of mechanical stress in modulating thermal denaturation of collagen.

The hyperthermia and thermal denaturation literatures reveal a time-temperature equivalency when heating cells or connective tissues: thermal damage increases with increasing temperature (for the same duration) and increases with increasing duration (for the same temperature). Recent findings conversely suggest that increasing the mechanical loading on a tissue during heating decreases the thermal damage (for a given temperature and duration of heating). Surprisingly, however, there are few histological correlates of such damage. In this paper, we show that progressive light microscopic changes - swelling of collagen bands, thickening of collagen-rich layers, hyalinization, and loss of birefringence approximately - correlate very well with both increased heating times and decreased mechanical loading. Increased mechanical stress is thus thermally protective and should be considered in the design of clinical procedures that use heating to treat diseases or injuries.

Animals↗

PubMed2005

Redistribution of strain and curvature in the porcine anterior lens capsule following a continuous circular capsulorhexis.

Cataract surgery is the most commonly performed surgical procedure in the US, it consists of three steps: introduction of a hole into the lens capsule, removal of the clouded lens through this access hole, and insertion of an artificial lens. We hypothesize that errant behavior by the residual epithelial cells of the lens capsule following surgery are due, in part, to surgically-induced changes of the native stress and strain fields in the lens capsule. Because the capsular bag can be regarded mechanically as a membrane, here we study changes in curvature and strains due to the most common means of introducing the initial access hole: a continuous circular capsulorhexis (CCC). We show that a modest sized CCC increases circumferential strains and decreases meridional strains by up to approximately 20% and that curvatures change by up to approximately 13%, particularly near the edge of the CCC. We submit that such changes can induce mechanobiological responses that are responsible, in part, for some of the long-term complications following cataract surgery.

Animals↗

PubMed2005

Multiaxial mechanical behavior of the porcine anterior lens capsule.

The biomechanics of the lens capsule of the eye is important both in physiologic processes such as accommodation and clinical treatments such as cataract surgery. Although the lens capsule experiences multiaxial stresses in vivo, there have been no measurements of its multiaxial properties or possible regional heterogeneities. Rather all prior mechanical data have come from 1-D pressure-volume or uniaxial force-length tests. Here, we report a new experimental approach to study in situ the regional, multiaxial mechanical behavior of the lens capsule. Moreover, we report multiaxial data suggesting that the porcine anterior lens capsule exhibits a typical nonlinear pseudo-elastic behavior over finite strains, that the in situ state is pre-stressed multi-axially, and that the meridional and circumferential directions are principal directions of strain, which is nearly equi-biaxial at the pole but less so towards the equator. Such data are fundamental to much needed constitutive formulations.

Animals↗

PubMed2005

Parameterization of the shape of intracranial saccular aneurysms using Legendre polynomials.

Our recent studies of the nonlinear mechanics of saccular aneurysms suggest that it is unlikely that these lesions enlarge or rupture via material (limit point) or dynamic (resonance) instabilities. Rather, there is a growing body of evidence from both vascular biology and biomechanical analyses that implicate mechanosensitive growth and remodeling processes. There is, therefore, a pressing need to quantify regional multiaxial wall stresses which, because of the membrane-like behavior of many aneurysms, necessitates better information on the applied loads and regional surface curvatures. Herein, we present and illustrate a method whereby regional curvatures can be estimated easily for sub-classes of human aneurysms based on clinically available data from magnetic resonance angiography (MRA). Whereas Legendre polynomials are used to illustrate this approach, different functions may prove useful for different sub-classes of lesions.

Algorithms↗

PubMed2005

Heat-induced changes in the finite strain viscoelastic behavioir of a collaagenous tissue.

Supra-physiological temperatures are increasingly being used to treat many different soft need for injuries. To identify improved clinical treatments, however, there is a need for better information on the effect of the mechanics on the thermal damage process as well as the effect of the incurred damage on the subsequent mechanical properties. In this paper we report the first biaxial data on the stress relaxation behavior of a collagenous tissue before and after thermal damage. Based on a two-dimensional finite strain viscoelastic model, which incorporates an exponential elastic response, it is shown that the thermal damage can significantly decrease the characteristic time for stress relaxation and the stress residual.

Animals↗

PubMed2005

A new paradigm for graduate research and training in the biomedical sciences and engineering.

98Emphasis on the individual investigator has fostered discovery for centuries, yet it is now recognized that the complexity of problems in the biomedical sciences and engineering requires collaborative efforts from individuals having diverse training and expertise. Various approaches can facilitate interdisciplinary interactions, but we submit that there is a critical need for a new educational paradigm for the way that we train biomedical engineers, life scientists, and mathematicians. We cannot continue to train graduate students in isolation within single disciplines, nor can we ask any one individual to learn all the essentials of biology, engineering, and mathematics. We must transform how students are trained and incorporate how real-world research and development are done-in diverse, interdisciplinary teams. Our fundamental vision is to create an innovative paradigm for graduate research and training that yields a new generation of biomedical engineers, life scientists, and mathematicians that is more diverse and that embraces and actively pursues a truly interdisciplinary, team-based approach to research based on a known benefit and mutual respect. In this paper, we describe our attempt to accomplish this via focused training in biomechanics, biomedical optics, mathematics, mechanobiology, and physiology. The overall approach is applicable, however, to most areas of biomedical research.

Biological Science Disciplines↗

PubMed2004

Effects of a sustained extension on arterial growth and remodeling: a theoretical study.

Three recent studies reveal that the unloaded length of a carotid artery increases significantly and rapidly in response to sustained increases in axial extension. Moreover, such lengthening involves an "unprecedented" increase in the rate of turnover of cells and matrix. Although current data are not sufficient for detailed biomechanical analyses, we present general numerical simulations that are consistent with the reported observations and support the hypothesis that rates of turnover correlate with the extent that stresses are perturbed from normal. In particular, a 3-D analysis of wall stress suggests that moderate (15%) increases in axial extension can increase the axial stress to a much greater extent than marked (50%) increases in blood pressure increase the circumferential stress. Furthermore, such increases in axial stress can occur without inducing significant gradients in stress within the wall. Consequently, we use a new, 2-D constrained mixture model to study evolving changes in the geometry, structure, and properties of carotid arteries in response to a sustained increase in axial extension. These simulations are qualitatively similar to the reports in the literature and support the notion that the stress-free lengths of individual constituents evolve during growth and remodeling.

Adaptation, Physiological↗

PubMed2004

A mixture model of arterial growth and remodeling in hypertension: altered muscle tone and tissue turnover.

Hypertension results in a thickening of the arterial wall due to a net increase in wall constituents via a coordinated production and removal of smooth muscle and extracellular matrix. Although many reports address the associated changes in material properties, few models address the biomechanics of the growth and remodeling process. In this paper, we employ a new, fundamentally different approach to modeling arterial adaptation in hypertension. In particular, basic, characteristic features of hypertension are simulated using a constrained mixture model wherein individual constituents can turnover at different rates and can have different natural configurations. We show, for example, that if there is no turnover of elastin (which approximates responses in maturity), the model vessel is able to reduce an early elevation in wall stress via a thickening of the wall even though the adaptation may be suboptimal. Conversely, if all constituents can turnover completely (which may approximate late development), the model vessel can restore the state of stress and material properties to native values. Given the potential of such a model, there is a need for more data on the history of turnover of individual constituents and their individual material properties.

Adaptation, Physiological↗

PubMed2004

On atomic force microscopy and the constitutive behavior of living cells.

Atomic force microscopy (AFM) is one of many new technologies available to study the mechanical properties and mechanobiological responses of living cells. Despite the widespread usage of this technology, there has been little attempt to develop new theoretical frameworks to interpret the associated data. Rather, most analyses rely on the classical Hertz solution for the indentation of an elastic half-space within the context of linearized elasticity. In contrast, we propose a fully nonlinear, constrained mixture model for adherent cells that allows one to account separately for the contributions of the three primary structural constituents of the cytoskeleton. Moreover, we extend a prior solution for a small indentation superimposed on a finite equibiaxial extension by incorporating in this mixture model for the special case of an initially random distribution of constituents (actin, intermediate filaments, and microtubules). We submit that this theoretical framework will allow an improved interpretation of indentation force-depth data from a sub-class of atomic force microscopy tests and will serve as an important analytical check for future finite element models. The latter will be necessary to exploit further the capabilities of both atomic force microscopy and nonlinear mixture theories for cell behavior.

Biomechanical Phenomena↗

PubMed2004

Redistribution of stress due to a circular hole in a nonlinear anisotropic membrane.

Many clinical procedures introduce holes into thin tissues that are typically under multiaxial stresses and finite strains. Such incisions change the stresses and strains from their homeostatic values, which may induce cells to alter their orientation and cytoskeletal organization as well as to migrate, proliferate, change their synthesis of matrix, or even to enter the cell death cycle. To correlate such changes in cellular activity with changes in the mechanics, we need solutions for the native and the perturbed boundary value problems. Such problems will often be complex and require a finite element solution; weak solutions should be evaluated independently, however, at least for special cases. Herein, we present a numerical solution of the governing nonlinear ordinary differential equation for the special case of stress redistribution due to the introduction of a circular hole into a finitely deformed, Fung-type, circular membrane that exhibits a cylindrical orthotropy. Among other results, we show that the anisotropy plays an increasingly greater role as the size of the hole becomes smaller, which is of course a goal of minimally invasive procedures.

Algorithms↗

PubMed2004

A 2-D model of flow-induced alterations in the geometry, structure, and properties of carotid arteries.

Evidence from diverse investigations suggests that arterial growth and remodeling correlates well with changes in mechanical stresses from their homeostatic values. Ultimately, therefore, there is a need for a comprehensive theory that accounts for changes in the 3-D distribution of stress within the arterial wall, including residual stress, and its relation to the mechanisms of mechanotransduction. Here, however, we consider a simpler theory that allows competing hypotheses to be tested easily, that can provide guidance in the development of a 3-D theory, and that may be useful in modeling solid-fluid interactions and interpreting clinical data. Specifically, we present a 2-D constrained mixture model for the adaptation of a cylindrical artery in response to a sustained alteration in flow. Using a rule-of-mixtures model for the stress response and first order kinetics for the production and removal of the three primary load-bearing constituents within the wall, we illustrate capabilities of the model by comparing responses given complete versus negligible turnover of elastin. Findings suggest that biological constraints may result in suboptimal adaptations, consistent with reported observations. To build upon this finding, however, there is a need for significantly more data to guide the hypothesis testing as well as the formulation of specific constitutive relations within the model.

Animals↗

PubMed2004

Altered mechanical behavior of epicardium under isothermal biaxial loading.

Most soft tissues that are treated clinically via heating experience multiaxial states of stress and strain in vivo and are subject to complex constraints during treatment. Remarkably, however, there are no prior data on changes in the multiaxial mechanical behavior of a collagenous tissue subjected to isometric constraints during heating. This paper presents the first biaxial stress-stretch data on a collagenous membrane (epicardium) before and after heating while subjected to various biaxial isometric constraints. It was found that isometric heating does not allow the increase in stiffness at low strains that occurs following isotonic heating. Moreover increasing the degree of stretch prior to heating increased the thermal stability of the tissue consistent with the concept that mechanical loading primarily affects the activation entropy, not the activation energy.

Animals↗

PubMed2004

A multiaxial computer-controlled organ culture and biomechanical device for mouse carotid arteries.

Much of our understanding of vascular mechanotransduction has come from studies using either cell culture or in vivo animal models, but the recent success of organ culture systems offers an exciting alternative. In studying cell-mediated vascular adaptations to altered loading, organ culture allows one to impose well-controlled mechanical loads and to perform multiaxial mechanical tests on the same vessel throughout the culture period, and thereby to observe cell-mediated vascular adaptations independent of neural and hormonal effects. Here, we present a computer-controlled perfused organ culture and biomechanical testing device designed for small caliber (50-5000 micron) blood vessels. This device can control precisely the pulsatile pressure, luminal flow, and axial load (or stretch) and perform intermittent biaxial (pressure-diameter and axial load-length) and functional tests to quantify adaptations in mechanical behavior and cellular function, respectively. Device capabilities are demonstrated by culturing mouse carotid arteries for 4 days.

Animals↗