Tendon exhibits anisotropic, inhomogeneous and viscoelastic mechanical properties that are determ... more Tendon exhibits anisotropic, inhomogeneous and viscoelastic mechanical properties that are determined by its complicated hierarchical structure and varying amounts/organization of different tissue constituents. Although extensive research has been conducted to use modelling approaches to interpret tendon structure-function relationships in combination with experimental data, many issues remain unclear (i.e. the role of minor components such as decorin, aggrecan and elastin), and the integration of mechanical analysis across different length scales has not been well applied to explore stress or strain transfer from macro- to microscale. This review outlines mathematical and computational models that have been used to understand tendon mechanics at different scales of the hierarchical organization. Model representations at the molecular, fibril and tissue levels are discussed, including formulations that follow phenomenological and microstructural approaches (which include evaluations of crimp, helical structure and the interaction between collagen fibrils and proteoglycans). Multiscale modelling approaches incorporating tendon features are suggested to be an advantageous methodology to understand further the physiological mechanical response of tendon and corresponding adaptation of properties owing to unique in vivo loading environments.
The manner in which strains are passed down the hierarchical length scales of tendons dictates ho... more The manner in which strains are passed down the hierarchical length scales of tendons dictates how cells within the collagen network regulate the tissue response to loading. How tendons deform in different hierarchical levels under shear and compression is unknown. The aims of this study were: (1) to evaluate whether specific regions of bovine deep digital flexor tendons exhibited different strain attenuation from macro to micro length scales, and (2) to elucidate mechanisms responsible for tendon deformation under shear and compression. Samples from distal and proximal regions of flexor tendons were subjected to three-step incremental stress-relaxation tests. Images of tissue markers, photobleached lines on collagen fibers, and nuclei locations were collected before and after loading. Results showed that strain transfer was attenuated from tissue to local matrix under both shear and compression. Nuclear aspect ratios exhibited smaller changes for distal samples, suggesting that cells are more shielded from deformation in the distal region. Collagen fiber sliding was observed to contribute significantly in response to shear, while uncrimping and fiber reorganization were the predominant mechanisms under compression. This study provides insight into microscale mechanisms responsible for multiscale strain attenuation of tendons under non-tensile macroscale loading. This article is protected by copyright. All rights reserved.
Variations in properties, active behavior, injury, scarring, and/or disease can all cause a tissu... more Variations in properties, active behavior, injury, scarring, and/or disease can all cause a tissue's mechanical behavior to be heterogeneous. Advances in imaging technology allow for accurate full-field displacement tracking of both in vitro and in vivo deformation from an applied load. While detailed strain fields provide some insight into tissue behavior, material properties are usually determined by fitting stress-strain behavior with a constitutive equation. However, the determination of the mechanical behavior of heterogeneous soft tissue requires a spatially varying constitutive equation (i.e., one in which the material parameters vary with position). We present an approach that computationally dissects the sample domain into many homogeneous subdomains, wherein subdomain boundaries are formed by applying a betweenness based graphical analysis to the deformation gradient field to identify locations with large discontinuities. This novel partitioning technique successfully determined the shape, size and location of regions with locally similar material properties for: (1) a series of simulated soft tissue samples prescribed with both abrupt and gradual changes in anisotropy strength, prescribed fiber alignment, stiffness, and nonlinearity, (2) tissue analogs (PDMS and collagen gels) which were tested biaxially and speckle tracked (3) and soft tissues which exhibited a natural variation in properties (cadaveric supraspinatus tendon), a pathologic variation in properties (thoracic aorta containing transmural plaque), and active behavior (contracting cardiac sheet). The routine enables the dissection of samples computationally rather than physically, allowing for the study of small tissues specimens with unknown and irregular inhomogeneity.
Tendons in different locations function in unique, and at times complex, in vivo loading environm... more Tendons in different locations function in unique, and at times complex, in vivo loading environments. Specifically, some tendons are subjected to compression, shear and/or torsion in addition to tensile loading, which play an important role in regulating tendon properties. To date, there have been few studies evaluating tendon mechanics when loaded in compression and shear, which are particularly relevant for understanding tendon regions that experience such non-tensile loading during normal physiologic function. The objective of this study was to evaluate mechanical responses of different regions of bovine deep digital flexor tendons (DDFT) under compressive and shear loading, and correlate structural characteristics to functional mechanical properties. Distal and proximal regions of DDFT were evaluated in a custom-made loading system via three-step incremental stress-relaxation tests. A two-relaxation-time solid linear model was used to describe the viscoelastic response. Results...
ASME 2012 Summer Bioengineering Conference, Parts A and B, 2012
ABSTRACT Naturally-occurring extracellular matrix (ECM) proteins, e.g. collagen I and fibrin, pla... more ABSTRACT Naturally-occurring extracellular matrix (ECM) proteins, e.g. collagen I and fibrin, play an important role in tissues, conferring structural integrity and providing a biochemical environment for eliciting important cellular responses (e.g. migration). Tissue engineers use a variety of matrix polymers as initial scaffolds for seeding cells, sometimes in combination with one another (e.g. collagen-fibrin [1]). For example, our group fabricates arterial tissue equivalents (TEs) by seeding cells in a fibrin gel, which is gradually degraded over time and replaced by cell-produced collagen [2]. While the structure and mechanics of individual ECM proteins have been studied extensively, how multiple fibrillar networks interact to confer overall mechanical behavior remains poorly understood. Narrowing this gap in knowledge of scaffolds comprising multiple fibril networks is crucial in allowing for more rational design in tissue engineering, as cells react differently according to their mechanical environments. For collagen-fibrin networks in particular, early efforts in elucidating interactions between these two fibril networks in co-gels have proven inconclusive due to inconsistent findings from various groups. Recent modeling efforts by our group have shown that simple “series” and “parallel” type interactions provide bounds for the mechanical behavior of collagen-fibrin co-gels [3]. In addition, experiments on pure collagen and fibrin vs. their respective networks from collagen-fibrin co-gels after digestion showed slight differences in mechanical behavior [4]. These previous studies have focused on the composition-function relationship between collagen and fibrin. The objective of the current work is to explore how collagen network architecture changes in the presence of the fibrin network in collagen-fibrin co-gels, thereby providing an added dimension to our understanding of collagen-fibrin systems by elucidating structure-composition-function relationships between collagen and fibrin.
ASME 2009 Summer Bioengineering Conference, Parts A and B, 2009
ABSTRACT Tendon tissue is composed of collagen fibers in a hydrated proteoglycan matrix. Although... more ABSTRACT Tendon tissue is composed of collagen fibers in a hydrated proteoglycan matrix. Although many tendons have fibers that are highly aligned (e.g. flexor tendon), the supraspinatus tendon (SST) of the shoulder has significant distribution of fiber alignment [1]. The alignment and distribution of the fibers likely contributes to the nonlinear and anisotropic mechanical behavior, however this has not been demonstrated. Understanding the role of fiber structure on tendon mechanical behavior, that is, characterizing the structure-function relationships, is critical to evaluate the function of injured, degenerated, or healing tendons and would be invaluable in the design and assessment of tissue engineered tendon replacements. While a structurally based hyperelastic model has been developed for tendon [2], this model contained only a single fiber orientation, which is not adequate for the more distributed fiber structure in the SST. We have recently applied a hyperelastic model formulation that has distributed collagen fiber orientation developed by Gasser and colleagues for the arterial wall [3] to model a tendon analog made from nanofibrous scaffolds [4]. The objective of this study was to build on previous work to apply a hyperelastic fiber-reinforced constitutive model that includes a specific term for fiber distribution to the tensile mechanics of human SST and to evaluate the site-specific model material properties.
ASME 2009 Summer Bioengineering Conference, Parts A and B, 2009
ABSTRACT Rotator cuff tears may be due in part to the complex loading environment of the supraspi... more ABSTRACT Rotator cuff tears may be due in part to the complex loading environment of the supraspinatus tendon (SST). Previous research has reported inhomogeneous uniaxial tensile mechanical properties of human SST [1–2] and location-specific collagen fiber alignment distributions that are qualitatively more disperse than other tendons [3–4]. Our group recently measured fiber alignment under load of samples tested along the tendon long-axis and found that re-alignment occurs in the toe-region and varies by SST location [5]. However, the mechanical properties and effect of fiber alignment under more complex loads remain unknown. Examining the properties of SST when tested transverse to the tendon long-axis will evaluate tissue anisotropy and better elucidate possible mechanisms for tissue inhomogeneity and nonlinearity. Therefore, the objectives of this study are to 1) measure local fiber alignment during transverse tensile loading, 2) measure corresponding mechanical properties, and 3) examine structure-function relationships of SST. We hypothesize that 1) fibers will become less aligned during transverse testing, 2) mechanical properties will be greatest in the anterior and bursal locations, and 3) higher initial alignment will correspond to lower transverse tensile properties.
ASME 2011 Summer Bioengineering Conference, Parts A and B, 2011
ABSTRACT Extracellular matrix (ECM) proteins (e.g. collagen, elastin) play an important role in b... more ABSTRACT Extracellular matrix (ECM) proteins (e.g. collagen, elastin) play an important role in biological tissues. In addition to conferring mechanical strength to a tissue, the ECM provides a biochemical environment essential for modulation of cellular responses such as growth and migration. Collagens are the dominant protein of the ECM, with collagen type I being most abundant. Our group and others have shown that the mechanical properties of a collagen I matrix change with collagen concentration, and when formed in the presence of a secondary fibril network such as fibrin [1]. We are interested in collagen-fibrin systems because our group uses fibrin as the starting scaffold material for cardiovascular tissue engineering, which produces interpenetrating collagen-fibrin matrices during the remodeling process as the fibrin network is degraded and replaced with cell-deposited collagen [2]. Fibrin and collagen networks are also present together around the thrombus during the wound healing process. Research has shown that ECM mechanical properties are correlated with their overall network structure characteristics such as fibril diameter [3]. Currently we have a modeling framework that generates an ECM microstructural network which can be used to predict the overall properties of a bioengineered tissue [4]. This framework allows exploration of the structure-function relation, but how the structure depends on composition remains poorly understood, especially in multi-component gels. Thus, the objective of this work was to quantify the collagen network architecture in pure collagen gels of different concentrations and in collagen-fibrin co-gels.
ASME 2010 Summer Bioengineering Conference, Parts A and B, 2010
ABSTRACT Few elastographic methods handle both anisotropy and inhomogeneity. Much of the focus ha... more ABSTRACT Few elastographic methods handle both anisotropy and inhomogeneity. Much of the focus has been on inhomogeneous materials that are locally isotropic. However, most load-bearing tissues (heart, ligament, blood vessels) are highly anisotropic, and the underlying structure is distinct and essential for function. With disease or damage, this structure is altered, and hence the potential for an elastographic tool that identifies regional changes in anisotropy is high. In this study we present a generalized anisotropic inverse mechanics (GAIM) method that is applicable to soft tissues and demonstrate its performance on tissue equivalents which serve as a convenient test case due to their inhomogeneity and the ease of pre-specifying the fiber alignment pattern.
ASME 2011 Summer Bioengineering Conference, Parts A and B, 2011
ABSTRACT Most elastographic methods applied to soft tissues assume either isotropy or homogeneity... more ABSTRACT Most elastographic methods applied to soft tissues assume either isotropy or homogeneity in the sample. While this assumption is valid in specific cases, general methods that can identify regional changes in mechanical anisotropy have many advantages. Chiefly, such methods could quantify regional anisotropic material behavior on intact tissue samples especially when the tissue is heterogeneous and too small for standard tests. In this study we use an inverse mechanics method which handles both anisotropy and heterogeneity to track changes in mechanical anisotropy associated with remodeling in cell-compacted collagen tissue equivalents (TE), which are then compared with measurements from polarimetry to estimate the method’s accuracy.
ASME 2010 Summer Bioengineering Conference, Parts A and B, 2010
ABSTRACT Mathematical modeling approaches are frequently used to characterize and predict the mec... more ABSTRACT Mathematical modeling approaches are frequently used to characterize and predict the mechanics of biological soft tissues. Structurally-based continuum models, which describe the relationship of the constituents’ properties (i.e., collagen fibers, matrix) to overall tissue properties, require knowledge of the relationship between microscopic (fiber) and macroscopic (tissue) deformation. The most common and straightforward approach is the use of an affine model, which assumes that local fiber kinematics follow the global tissue deformation. Although the affine assumption is often used in constitutive modeling, several studies have reported non-affine fiber behavior in soft tissue testing [1–2]. Our recent work has quantified the anisotropic and inhomogeneous mechanical and organizational properties of human supraspinatus tendon (SST) [3–4]. We have also utilized a fiber dispersion model to examine SST [5]; however the relationship between macroscopic and microscopic deformation in this tendon remains unknown. Therefore, the purpose of this study was to examine the affine assumption in human SST fiber kinematics by comparing experimentally-measured fiber alignment to the affine model prediction.
The mechanical behavior of a three-dimensional cross-linked fiber network embedded in matrix is s... more The mechanical behavior of a three-dimensional cross-linked fiber network embedded in matrix is studied in this work. The network is composed from linear elastic fibers which store energy only in the axial deformation mode, while the matrix is also isotropic and linear elastic. Such systems are encountered in a broad range of applications, from tissue to consumer products. As the matrix modulus increases, the network is constrained to deform more affinely. This leads to internal forces acting between the network and the matrix, which produce strong stress concentration at the network cross-links. This interaction increases the apparent modulus of the network and decreases the apparent modulus of the matrix. A model is developed to predict the effective modulus of the composite and its predictions are compared with numerical data for a variety of networks.
Heparan sulfate proteoglycans act as co-receptors for many chemokines and growth factors. The sul... more Heparan sulfate proteoglycans act as co-receptors for many chemokines and growth factors. The sulfation pattern of the heparan sulfate chains is a critical regulatory step affecting the binding of chemokines and growth factors. N-deacetylase-N-sulfotransferase1 (Ndst1) is one of the first enzymes to catalyze sulfation. Previously published work has shown that HSPGs alter tangent moduli and stiffness of tissues and cells. We hypothesized that loss of Ndst1 in smooth muscle would lead to significant changes in heparan sulfate modification and the elastic properties of arteries. In line with this hypothesis, the axial tangent modulus was significantly decreased in aorta from mice lacking Ndst1 in smooth muscle (SM22αcre(+)Ndst1(-/-), p < 0.05, n = 5). The decrease in axial tangent modulus was associated with a significant switch in myosin and actin types and isoforms expressed in aorta and isolated aortic vascular smooth muscle cells. In contrast, no changes were found in the compliance of smaller thoracodorsal arteries of SM22αcre(+)Ndst1(-/-) mice. In summary, the major findings of this study were that targeted ablation of Ndst1 in smooth muscle cells results in altered biomechanical properties of aorta and differential expression of myosin and actin types and isoforms.
Tendon exhibits anisotropic, inhomogeneous and viscoelastic mechanical properties that are determ... more Tendon exhibits anisotropic, inhomogeneous and viscoelastic mechanical properties that are determined by its complicated hierarchical structure and varying amounts/organization of different tissue constituents. Although extensive research has been conducted to use modelling approaches to interpret tendon structure-function relationships in combination with experimental data, many issues remain unclear (i.e. the role of minor components such as decorin, aggrecan and elastin), and the integration of mechanical analysis across different length scales has not been well applied to explore stress or strain transfer from macro- to microscale. This review outlines mathematical and computational models that have been used to understand tendon mechanics at different scales of the hierarchical organization. Model representations at the molecular, fibril and tissue levels are discussed, including formulations that follow phenomenological and microstructural approaches (which include evaluations of crimp, helical structure and the interaction between collagen fibrils and proteoglycans). Multiscale modelling approaches incorporating tendon features are suggested to be an advantageous methodology to understand further the physiological mechanical response of tendon and corresponding adaptation of properties owing to unique in vivo loading environments.
The manner in which strains are passed down the hierarchical length scales of tendons dictates ho... more The manner in which strains are passed down the hierarchical length scales of tendons dictates how cells within the collagen network regulate the tissue response to loading. How tendons deform in different hierarchical levels under shear and compression is unknown. The aims of this study were: (1) to evaluate whether specific regions of bovine deep digital flexor tendons exhibited different strain attenuation from macro to micro length scales, and (2) to elucidate mechanisms responsible for tendon deformation under shear and compression. Samples from distal and proximal regions of flexor tendons were subjected to three-step incremental stress-relaxation tests. Images of tissue markers, photobleached lines on collagen fibers, and nuclei locations were collected before and after loading. Results showed that strain transfer was attenuated from tissue to local matrix under both shear and compression. Nuclear aspect ratios exhibited smaller changes for distal samples, suggesting that cells are more shielded from deformation in the distal region. Collagen fiber sliding was observed to contribute significantly in response to shear, while uncrimping and fiber reorganization were the predominant mechanisms under compression. This study provides insight into microscale mechanisms responsible for multiscale strain attenuation of tendons under non-tensile macroscale loading. This article is protected by copyright. All rights reserved.
Variations in properties, active behavior, injury, scarring, and/or disease can all cause a tissu... more Variations in properties, active behavior, injury, scarring, and/or disease can all cause a tissue's mechanical behavior to be heterogeneous. Advances in imaging technology allow for accurate full-field displacement tracking of both in vitro and in vivo deformation from an applied load. While detailed strain fields provide some insight into tissue behavior, material properties are usually determined by fitting stress-strain behavior with a constitutive equation. However, the determination of the mechanical behavior of heterogeneous soft tissue requires a spatially varying constitutive equation (i.e., one in which the material parameters vary with position). We present an approach that computationally dissects the sample domain into many homogeneous subdomains, wherein subdomain boundaries are formed by applying a betweenness based graphical analysis to the deformation gradient field to identify locations with large discontinuities. This novel partitioning technique successfully determined the shape, size and location of regions with locally similar material properties for: (1) a series of simulated soft tissue samples prescribed with both abrupt and gradual changes in anisotropy strength, prescribed fiber alignment, stiffness, and nonlinearity, (2) tissue analogs (PDMS and collagen gels) which were tested biaxially and speckle tracked (3) and soft tissues which exhibited a natural variation in properties (cadaveric supraspinatus tendon), a pathologic variation in properties (thoracic aorta containing transmural plaque), and active behavior (contracting cardiac sheet). The routine enables the dissection of samples computationally rather than physically, allowing for the study of small tissues specimens with unknown and irregular inhomogeneity.
Tendons in different locations function in unique, and at times complex, in vivo loading environm... more Tendons in different locations function in unique, and at times complex, in vivo loading environments. Specifically, some tendons are subjected to compression, shear and/or torsion in addition to tensile loading, which play an important role in regulating tendon properties. To date, there have been few studies evaluating tendon mechanics when loaded in compression and shear, which are particularly relevant for understanding tendon regions that experience such non-tensile loading during normal physiologic function. The objective of this study was to evaluate mechanical responses of different regions of bovine deep digital flexor tendons (DDFT) under compressive and shear loading, and correlate structural characteristics to functional mechanical properties. Distal and proximal regions of DDFT were evaluated in a custom-made loading system via three-step incremental stress-relaxation tests. A two-relaxation-time solid linear model was used to describe the viscoelastic response. Results...
ASME 2012 Summer Bioengineering Conference, Parts A and B, 2012
ABSTRACT Naturally-occurring extracellular matrix (ECM) proteins, e.g. collagen I and fibrin, pla... more ABSTRACT Naturally-occurring extracellular matrix (ECM) proteins, e.g. collagen I and fibrin, play an important role in tissues, conferring structural integrity and providing a biochemical environment for eliciting important cellular responses (e.g. migration). Tissue engineers use a variety of matrix polymers as initial scaffolds for seeding cells, sometimes in combination with one another (e.g. collagen-fibrin [1]). For example, our group fabricates arterial tissue equivalents (TEs) by seeding cells in a fibrin gel, which is gradually degraded over time and replaced by cell-produced collagen [2]. While the structure and mechanics of individual ECM proteins have been studied extensively, how multiple fibrillar networks interact to confer overall mechanical behavior remains poorly understood. Narrowing this gap in knowledge of scaffolds comprising multiple fibril networks is crucial in allowing for more rational design in tissue engineering, as cells react differently according to their mechanical environments. For collagen-fibrin networks in particular, early efforts in elucidating interactions between these two fibril networks in co-gels have proven inconclusive due to inconsistent findings from various groups. Recent modeling efforts by our group have shown that simple “series” and “parallel” type interactions provide bounds for the mechanical behavior of collagen-fibrin co-gels [3]. In addition, experiments on pure collagen and fibrin vs. their respective networks from collagen-fibrin co-gels after digestion showed slight differences in mechanical behavior [4]. These previous studies have focused on the composition-function relationship between collagen and fibrin. The objective of the current work is to explore how collagen network architecture changes in the presence of the fibrin network in collagen-fibrin co-gels, thereby providing an added dimension to our understanding of collagen-fibrin systems by elucidating structure-composition-function relationships between collagen and fibrin.
ASME 2009 Summer Bioengineering Conference, Parts A and B, 2009
ABSTRACT Tendon tissue is composed of collagen fibers in a hydrated proteoglycan matrix. Although... more ABSTRACT Tendon tissue is composed of collagen fibers in a hydrated proteoglycan matrix. Although many tendons have fibers that are highly aligned (e.g. flexor tendon), the supraspinatus tendon (SST) of the shoulder has significant distribution of fiber alignment [1]. The alignment and distribution of the fibers likely contributes to the nonlinear and anisotropic mechanical behavior, however this has not been demonstrated. Understanding the role of fiber structure on tendon mechanical behavior, that is, characterizing the structure-function relationships, is critical to evaluate the function of injured, degenerated, or healing tendons and would be invaluable in the design and assessment of tissue engineered tendon replacements. While a structurally based hyperelastic model has been developed for tendon [2], this model contained only a single fiber orientation, which is not adequate for the more distributed fiber structure in the SST. We have recently applied a hyperelastic model formulation that has distributed collagen fiber orientation developed by Gasser and colleagues for the arterial wall [3] to model a tendon analog made from nanofibrous scaffolds [4]. The objective of this study was to build on previous work to apply a hyperelastic fiber-reinforced constitutive model that includes a specific term for fiber distribution to the tensile mechanics of human SST and to evaluate the site-specific model material properties.
ASME 2009 Summer Bioengineering Conference, Parts A and B, 2009
ABSTRACT Rotator cuff tears may be due in part to the complex loading environment of the supraspi... more ABSTRACT Rotator cuff tears may be due in part to the complex loading environment of the supraspinatus tendon (SST). Previous research has reported inhomogeneous uniaxial tensile mechanical properties of human SST [1–2] and location-specific collagen fiber alignment distributions that are qualitatively more disperse than other tendons [3–4]. Our group recently measured fiber alignment under load of samples tested along the tendon long-axis and found that re-alignment occurs in the toe-region and varies by SST location [5]. However, the mechanical properties and effect of fiber alignment under more complex loads remain unknown. Examining the properties of SST when tested transverse to the tendon long-axis will evaluate tissue anisotropy and better elucidate possible mechanisms for tissue inhomogeneity and nonlinearity. Therefore, the objectives of this study are to 1) measure local fiber alignment during transverse tensile loading, 2) measure corresponding mechanical properties, and 3) examine structure-function relationships of SST. We hypothesize that 1) fibers will become less aligned during transverse testing, 2) mechanical properties will be greatest in the anterior and bursal locations, and 3) higher initial alignment will correspond to lower transverse tensile properties.
ASME 2011 Summer Bioengineering Conference, Parts A and B, 2011
ABSTRACT Extracellular matrix (ECM) proteins (e.g. collagen, elastin) play an important role in b... more ABSTRACT Extracellular matrix (ECM) proteins (e.g. collagen, elastin) play an important role in biological tissues. In addition to conferring mechanical strength to a tissue, the ECM provides a biochemical environment essential for modulation of cellular responses such as growth and migration. Collagens are the dominant protein of the ECM, with collagen type I being most abundant. Our group and others have shown that the mechanical properties of a collagen I matrix change with collagen concentration, and when formed in the presence of a secondary fibril network such as fibrin [1]. We are interested in collagen-fibrin systems because our group uses fibrin as the starting scaffold material for cardiovascular tissue engineering, which produces interpenetrating collagen-fibrin matrices during the remodeling process as the fibrin network is degraded and replaced with cell-deposited collagen [2]. Fibrin and collagen networks are also present together around the thrombus during the wound healing process. Research has shown that ECM mechanical properties are correlated with their overall network structure characteristics such as fibril diameter [3]. Currently we have a modeling framework that generates an ECM microstructural network which can be used to predict the overall properties of a bioengineered tissue [4]. This framework allows exploration of the structure-function relation, but how the structure depends on composition remains poorly understood, especially in multi-component gels. Thus, the objective of this work was to quantify the collagen network architecture in pure collagen gels of different concentrations and in collagen-fibrin co-gels.
ASME 2010 Summer Bioengineering Conference, Parts A and B, 2010
ABSTRACT Few elastographic methods handle both anisotropy and inhomogeneity. Much of the focus ha... more ABSTRACT Few elastographic methods handle both anisotropy and inhomogeneity. Much of the focus has been on inhomogeneous materials that are locally isotropic. However, most load-bearing tissues (heart, ligament, blood vessels) are highly anisotropic, and the underlying structure is distinct and essential for function. With disease or damage, this structure is altered, and hence the potential for an elastographic tool that identifies regional changes in anisotropy is high. In this study we present a generalized anisotropic inverse mechanics (GAIM) method that is applicable to soft tissues and demonstrate its performance on tissue equivalents which serve as a convenient test case due to their inhomogeneity and the ease of pre-specifying the fiber alignment pattern.
ASME 2011 Summer Bioengineering Conference, Parts A and B, 2011
ABSTRACT Most elastographic methods applied to soft tissues assume either isotropy or homogeneity... more ABSTRACT Most elastographic methods applied to soft tissues assume either isotropy or homogeneity in the sample. While this assumption is valid in specific cases, general methods that can identify regional changes in mechanical anisotropy have many advantages. Chiefly, such methods could quantify regional anisotropic material behavior on intact tissue samples especially when the tissue is heterogeneous and too small for standard tests. In this study we use an inverse mechanics method which handles both anisotropy and heterogeneity to track changes in mechanical anisotropy associated with remodeling in cell-compacted collagen tissue equivalents (TE), which are then compared with measurements from polarimetry to estimate the method’s accuracy.
ASME 2010 Summer Bioengineering Conference, Parts A and B, 2010
ABSTRACT Mathematical modeling approaches are frequently used to characterize and predict the mec... more ABSTRACT Mathematical modeling approaches are frequently used to characterize and predict the mechanics of biological soft tissues. Structurally-based continuum models, which describe the relationship of the constituents’ properties (i.e., collagen fibers, matrix) to overall tissue properties, require knowledge of the relationship between microscopic (fiber) and macroscopic (tissue) deformation. The most common and straightforward approach is the use of an affine model, which assumes that local fiber kinematics follow the global tissue deformation. Although the affine assumption is often used in constitutive modeling, several studies have reported non-affine fiber behavior in soft tissue testing [1–2]. Our recent work has quantified the anisotropic and inhomogeneous mechanical and organizational properties of human supraspinatus tendon (SST) [3–4]. We have also utilized a fiber dispersion model to examine SST [5]; however the relationship between macroscopic and microscopic deformation in this tendon remains unknown. Therefore, the purpose of this study was to examine the affine assumption in human SST fiber kinematics by comparing experimentally-measured fiber alignment to the affine model prediction.
The mechanical behavior of a three-dimensional cross-linked fiber network embedded in matrix is s... more The mechanical behavior of a three-dimensional cross-linked fiber network embedded in matrix is studied in this work. The network is composed from linear elastic fibers which store energy only in the axial deformation mode, while the matrix is also isotropic and linear elastic. Such systems are encountered in a broad range of applications, from tissue to consumer products. As the matrix modulus increases, the network is constrained to deform more affinely. This leads to internal forces acting between the network and the matrix, which produce strong stress concentration at the network cross-links. This interaction increases the apparent modulus of the network and decreases the apparent modulus of the matrix. A model is developed to predict the effective modulus of the composite and its predictions are compared with numerical data for a variety of networks.
Heparan sulfate proteoglycans act as co-receptors for many chemokines and growth factors. The sul... more Heparan sulfate proteoglycans act as co-receptors for many chemokines and growth factors. The sulfation pattern of the heparan sulfate chains is a critical regulatory step affecting the binding of chemokines and growth factors. N-deacetylase-N-sulfotransferase1 (Ndst1) is one of the first enzymes to catalyze sulfation. Previously published work has shown that HSPGs alter tangent moduli and stiffness of tissues and cells. We hypothesized that loss of Ndst1 in smooth muscle would lead to significant changes in heparan sulfate modification and the elastic properties of arteries. In line with this hypothesis, the axial tangent modulus was significantly decreased in aorta from mice lacking Ndst1 in smooth muscle (SM22αcre(+)Ndst1(-/-), p < 0.05, n = 5). The decrease in axial tangent modulus was associated with a significant switch in myosin and actin types and isoforms expressed in aorta and isolated aortic vascular smooth muscle cells. In contrast, no changes were found in the compliance of smaller thoracodorsal arteries of SM22αcre(+)Ndst1(-/-) mice. In summary, the major findings of this study were that targeted ablation of Ndst1 in smooth muscle cells results in altered biomechanical properties of aorta and differential expression of myosin and actin types and isoforms.
Uploads
Papers by Spencer Lake