Qian Wang | Ohio State University (original) (raw)

Biomechanics and Sports Medicine by Qian Wang

Background This study compared immediate versus delayed massage-like compressive loading on skel... more Background

This study compared immediate versus delayed massage-like compressive loading on skeletal muscle viscoelastic properties following eccentric exercise.

Methods

Eighteen rabbits were surgically instrumented with peroneal nerve cuffs for stimulation of the tibialis anterior muscle. Rabbits were randomly assigned to a massage loading protocol applied immediately post exercise (n = 6), commencing 48 h post exercise (n = 6), or exercised no-massage control (n = 6). Viscoelastic properties were evaluated in vivo by performing a stress-relaxation test pre- and post-exercise and daily pre- and post-massage for four consecutive days of massage loading. A quasi-linear viscoelastic approach modeled the instantaneous elastic response (AG0), fast (g1p) and slow (g2p) relaxation coefficients, and the corresponding relaxation time constants τ1 and τ2.

Findings

Exercise increased AG0 in all groups (P < 0.05). After adjusting for the three multiple comparisons, recovery of AG0 was not significant in the immediate (P = 0.021) or delayed (P = 0.048) group compared to the control group following four days of massage. However, within-day (pre- to post-massage) analysis revealed a decrease in AG0 in both massage groups. Following exercise, g1p increased and g2p and τ1 decreased for all groups (P < 0.05). Exercise had no effect on τ2 (P > 0.05). After four days of massage, there was no significant recovery of the relaxation parameters for either massage loading group compared to the control group.

Interpretation

Our findings suggest that massage loading following eccentric exercise has a greater effect on reducing muscle stiffness, estimated by AG0, within-day rather than affecting recovery over multiple days. Massage loading also has little effect on the relaxation response.

—Massage therapy has a long history and has been widely believed effective in restoring tissue fu... more —Massage therapy has a long history and has been widely believed effective in restoring tissue function, relieving pain and stress, and promoting overall well-being. However, the application of massage-like actions and the efficacy of massage are largely based on anecdotal experiences that are difficult to define and measure. This leads to a somewhat limited evidence-based interface of massage therapy with modern medicine. In this study, we introduce a mechatronic device that delivers highly reproducible massage-like mechanical loads to the hind limbs of small animals (rats and rabbits), where various massage-like actions are quantified by the loading parameters (magnitude, frequency and duration) of the compressive and transverse forces on the subject tissues. The effect of massage is measured by the difference in passive viscoelastic properties of the subject tissues before and after mechanical loading, both obtained by the same device. Results show that this device is useful in identifying the loading parameters that are most conducive to a change in tissue mechanical properties, and can determine the range of loading parameters that result in sustained changes in tissue mechanical properties and function. This device presents the first step in our effort for quantifying the application of massage-like actions used clinically and measurement of their efficacy that can readily be combined with various quantitative measures (e.g., active mechanical properties and physiological assays) for determining the therapeutic and mechanistic effects of massage therapies.

A quasi-linear viscoelasticity (QLV) model was used to study passive time-dependent responses of ... more A quasi-linear viscoelasticity (QLV) model was used to study passive time-dependent responses of skeletal muscle to repeated massage-like compressive loading (MLL) following damaging eccentric exercise. Six skeletally mature rabbits were surgically instrumented with bilateral peroneal nerve cuffs for stimulation of the hindlimb tibialis anterior (TA) muscles. Following the eccentric exercise, rabbits were randomly assigned to a four-day MLL protocol mimicking deep effleurage (0.5 Hz, 10 N for 15 min or for 30 min). The contralateral hindlimb served as the exercised, no-MLL control for both MLL conditions. Viscoelastic properties of the muscle pre-exercise, post-exercise on Day 1, and pre-and post-MLL Day 1 through Day 4 were determined with ramp-and-hold tests. The instantaneous elastic response (AG 0) increased following exercise (po 0.05) and decreased due to both the 15 min and 30 min four-day MLL protocols (po 0.05). Post-four days of MLL the normalized AG 0 decreased from post-exercise (Day 1, 248.5%) to the post-MLL (Day 4, 98.5%) (p o0.05), compared to the no-MLL group (Day 4, 222.0%) (p o 0.05). Exercise and four-day MLL showed no acute or cumulative effects on the fast and slow relaxation coefficients (p 40.05). This is the first experimental evidence of the effect of both acute (daily) and cumulative changes in viscoelastic properties of intensely exercised muscle due to ex vivo MLL. It provides a starting point for correlating passive muscle properties with mechanical effects of manual therapies, and may shed light on design and optimization of massage protocols.

BioMEMS and Cell biomechanics by Qian Wang

Mechanical stretching and topographical cues are both effective mechanical stimulations for regul... more Mechanical stretching and topographical cues are both effective mechanical stimulations for regulating cell morphology, orientation, and behaviors. The competition of these two mechanical stimulations remains largely underexplored. Previous studies have suggested that a small cyclic mechanical strain is not able to reorient cells that have been pre-aligned by relatively large linear microstructures, but can reorient those pre-aligned by small linear micro/nanostructures if the characteristic dimension of these structures is below a certain threshold. Likewise, for micro/nanostructures with a given characteristic dimension, the strain must exceed a certain magnitude to overrule the topographic cues. There are however no in-depth investigations of such “thresholds” due to the lack of close examination of dynamic cell orientation during and shortly after the mechanical loading. In this study, the time-dependent combinatory effects of active and passive mechanical stimulations on cell orientation are investigated by developing a micromechanical stimulator. The results show that the cells pre-aligned by linear micro/nanostructures can be altered by cyclic in-plane strain, regardless of the structure size. During the loading, the micro/nanostructures can resist the reorientation effects by cyclic in-plane strain while the resistive capability (measured by the mean orientation angle change and the reorientation speed) increases with the increasing characteristic dimension. The micro/nanostructures also can recover the cell orientation after the cessation of cyclic in-plane strain, while the recovering capability increases with the characteristic dimension. The previously observed thresholds are largely dependent on the observation time points. In order to accurately evaluate the combinatory effects of the two mechanical stimulations, observations during the active loading with a short time interval or endpoint observations shortly after the loading are preferred. This study provides a microengineering solution to investigate the time-dependent combinatory effects of the active and passive mechanical stimulations and is expected to enhance our understanding of cell responses to complex mechanical environments.

Fluid shear stress (FSS) plays a critical role in regulating endothelium function and maintaining... more Fluid shear stress (FSS) plays a critical role in regulating endothelium function and maintaining vascular homeostasis. Current microfluidic devices for studying FSS effects on cells either separate high shear stress zone and low shear stress zone into different culturing chambers, or arranging the zones serially along the flow direction, which complicates subsequent data interpretation. In this paper, we report a diamond shaped microfluidic shear device where the high shear stress zone and the low shear stress zone are arranged in parallel within one culturing chamber. Since the zones with different shear stress magnitudes are aligned normal to the flow direction, the cells in one stress group are not substantially affected by the flow-induced cytokine/chemokine releases by cells in the other group. Cell loading experiments using human umbilical vein endothelial cells show that the device is able to reveal stress magnitude-dependent and loading duration-dependent cell responses. The co-existence of shear stress zones with varied magnitudes within the same culturing chamber not only ensures that all the cells are subject to the identical culturing conditions, but also allows the resemblance of the differential shear stress pattern in natural arterial conditions. The device is expected to provide a new solution for studying the effects of heterogeneous hemodynamic patterns in the onset and progression of various vascular diseases.

Intercellular electromechanical transduction in adult cardiac myocytes plays an important role in... more Intercellular electromechanical transduction in adult cardiac myocytes plays an important role in regulating heart function. The efficiency of intercellular electromechanical transduction has so far been investigated only to a limited extent, which is largely due to the lack of appropriate tools that can quantitatively assess the contractile performance of interconnected adult cardiac myocytes. In this paper we report a microengineered device that is capable of applying electrical stimulation to the selected adult cardiac myocyte in a longitudinally connected cell doublet and quantifying the intercellular electro-mechanical transduction by measuring the contractile performance of stimulated and un-stimulated cells in the same doublet. The capability of applying selective electrical stimulation on only one cell in the doublet is validated by examining cell contractile performance while blocking the intercellular communication. Quantitative assessment of cell contractile performance in isolated adult cardiac myocytes is performed by measuring the change in cell length. The proof-of-concept assessment of gap junction performance shows that the device is useful in studying the efficiency of gap junctions in adult cardiac myocytes, which is most relevant to the synchronized pumping performance of native myocardium. Collectively, this work provides a quantitative tool for studying intercellular electromechanical transduction and is expected to develop a comprehensive understanding of the role of intercellular communication in various heart diseases.

Mechanical stimuli regulate cell structure and function during physiological processes. To unders... more Mechanical stimuli regulate cell structure and function during physiological processes. To understand the role of mechanical stimuli, engineered devices are developed to deliver controllable mechanical signals to cells cultured in vitro. Localized mechanical loading on selected cells are preferred when investigating intercellular communication. In this work, we fabricated and characterized a polydimethylsiloxane (PDMS) micro-device for applying controlled compressive/tensile loads to selected live cells. The device consists of nine circular PDMS membranes serving as the loading sites; the loading parameters at each site are individually controllable. The in-plane strain upon PDMS membrane deflection was experimentally characterized. The result showed that for a circular membrane with 500 μm in diameter and 60 μm thick, the radial strain from −6% (compressive) to 25% (tensile) can be achieved at the membrane center. This device allows localized cell loading with minimal fabrication/operation complexity and ease of scaling-up. It is expected to foster the development of high throughput mechanical loading systems for a broad array of cellular mechanobiological studies.

To investigate complicated mechanobiological events at the cellular level, microdevices that are ... more To investigate complicated mechanobiological events at the cellular level, microdevices that are capable of delivering controlled and identical mechanical signals to multiple loading sites are of imperative need. Although current devices in this field can generate identical loads under static conditions, parallel delivery of dynamic loads with identical loading parameters often requires the use of a multi-channel pump or multiple pumps to avoid the differential patterns of load magnitudes caused by the compliant fluidic channels. This however increases the complexity of the devices and somewhat compromises the miniaturization nature. In this study, we design and fabricate a bi-layered microfluidic device driven by a single external pump that can simultaneously deliver identical strain profiles to all the loading membranes (each with 500 m in diameter). The loading performances under both static and cyclic loading conditions were experimentally examined. The influences of the total membrane number and the loading frequency were also examined. By minimizing the number of external pumping units for parallel operation , this device allows further miniaturization of on-chip mechanical stimulators for various studies in the field of cellular mechanobiology.

Cellular mechanical stimulators with multi-plexing and high-throughput capability often use multi... more Cellular mechanical stimulators with multi-plexing and high-throughput capability often use multiple external pumps, which compromise simplicity and minia-turization. In this study, we report a bilayered microfluidic device driven by one single pump to deliver in-plane surface strains toward four membranes with proportional center strain magnitudes. The maximal strain magnitudes exhibited a constant proportionality (i.e., 1:2:3:4) under both static and dynamic loading conditions. The influences of the loading frequency and the total membrane number were examined. Proof-of-concept cell loading showed that the device can be used to investigate magnitude-dependent cell responses to mechanical stimuli, thus promising broad applications in cell mechanobiological studies where delivery of mechanical signals with controlled and varying magnitudes toward multiple loading sites is needed.

This paper reports a micromechanical stimulator that applies both in-plane mechanical strains and... more This paper reports a micromechanical stimulator that applies both in-plane mechanical strains and periodic wrinkled topographical cues towards live cells for studying the synergistic effects of passive and active mechanical stimulations on cells. The results showed that cell alignment regulated by microscale wrinkled topographies can be altered by cyclic tensile strain, and quickly recover within a few hours after strain removal. This suggests that timely observation of cell alignment following strain removal is critical for revealing the dynamic cell response to these two mechanical cues. INTRODUCTION Cell alignment has been widely observed in vivo and has been known to play a critical role in tissue development and regeneration, e.g. pattern formation during embryogenesis and regulation of contractile strength in musculoskeletal tissues. Aligning the cells in a desired pattern in vitro is therefore essential for cell mechanobiological studies and tissue engineering applications. It has been demonstrated that cell alignment can be regulated by either passive mechanical stimulation (e.g. topographic guidance) or active mechanical stimulation (e.g. cyclic loading) alone. Studies on the synergistic effects of active and passive mechanical stimulations revealed that cells always retain their alignment on linear microscale structures during cyclic uniaxial straining, independent of the strain magnitude [1]; but lose their alignment on linear nanoscale substrates during cyclic uniaxial straining [2]. The distinct effects of microscale and nanoscale topographies have not been justified. In particular, it is not clear why the cells on linear microscale structures would not respond to mechanical strain that can lure them to align along the transverse direction in the presence of linear nanoscale structures or without the presence of topographic cues.

This work reports the development of a polymeric micromechanical device to provide mechanical sti... more This work reports the development of a polymeric micromechanical device to provide mechanical stimulation to three-dimensional (3D) cell aggregates that are a few hundred of m in size. Different from current loading technologies for 3D cultured cells, the device allows for the application of individually adjustable mechanical stimulation to a number of 3D cell aggregates, thus allowing parallel operation for in-depth investigation of loading parameter-dependent cell responses. Proof-of-concept experiments showed that the unique strain pattern generated by this device is able to guide the differentiation of embryonic stem cells towards a specific direction without the use of chemical inducing factors. This work indicates that 3D mechanical stimuli can be a promising inducing factor for regulating stem cell differentiation.

A polymer-based microdevice that can deliver mechanical strain with controllable strain gradient ... more A polymer-based microdevice that can deliver mechanical strain with controllable strain gradient to in vitro cultured cells is presented. The polymer membrane with varying thickness is fabricated using a modified double-side replica molding process. Bi-axial strain is generated on the top surface of the membrane by applying differential hydraulic pressure on the membrane. The strain profile is analyzed numerically and experimentally. The results indicate that the strain gradient can be controlled by changing the thickness profile of the polymer membrane. The goal of this work is to provide an on-chip tool for quantitative intercellular mechanotransduction study to examine the influence of strain gradient on cellular behaviors. INTRODUCTION Live cells are constantly subjected to mechanical signals originating from their extracellular and intracellular environments. These mechanical signals are critical for maintaining cellular functions under various physiological conditions. To quantitatively understand the effects of these mechanical signals, many studies have been performed by applying various mechanical loads to in vitro cultured cells [1, 2]. A simple and popular method is to apply the loads by stretching a thin polymer membrane where the cells are cultured. In this method, magnitude of the mechanical strain can be controlled using differential pressure or other actuation means [3]. However, the strain gradient, another potent regulator of cellular mechano-transduction, is poorly controllable. This paper presents a polymer-based cell loading device which have loading membranes with a varying thickness. When deformed by a differential pressure, these membranes exhibit different strain gradients depending on different thickness profiles. The work thus promises a potential in studying the influence of strain gradient on cellular behavior and intercellular communication.

This work reports the development of a polydimethylsiloxane (PDMS) microdevice for intercellular ... more This work reports the development of a polydimethylsiloxane (PDMS) microdevice for intercellular mechanical transduction study. Uni-axial strain with spatial gradient was generated by deforming a rectangular PDMS membrane. The strain distribution was experimentally measured. NIH 3T3 fibroblasts are cultured on the membrane and subjected to cyclic loading. Remarkable cell reorientation is observed in different strain regions. Analysis shows that cell morphological change in low strain region is due to intercellular mechanical transduction with the cells in the neighboring high strain region. Intercellular mechanical transduction can thus be quantitatively assessed.

Adaptive Optics by Qian Wang

Liquid lens offers a simple solution to achieve tunable optical powers. This approach, however, s... more Liquid lens offers a simple solution to achieve tunable optical powers. This approach, however, suffers from deteriorated resolution at high diopters. In this study, a plano-convex liquid lens with aspherical cross-section is developed. Such configuration allows for the lens profiles at high diopters to be close to spherical shapes by alleviating the edge-clamping effects. Resolution tests of a 6mm lens with optimized asphericity exhibit improved resolutions in both center and peripheral regions at 40 and 100 diopters than the lenses with planar membranes. It shows that aspherical membranes can improve the resolving power of liquid lenses at high diopters, thus providing a new route of optimizing the imaging performance of adaptive liquid lenses for various applications.

Background This study compared immediate versus delayed massage-like compressive loading on skel... more Background

This study compared immediate versus delayed massage-like compressive loading on skeletal muscle viscoelastic properties following eccentric exercise.

Methods

Findings

Interpretation