Academic literature on the topic 'MSK Tissue Loading'
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Journal articles on the topic "MSK Tissue Loading"
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Hart, David A., Ronald F. Zernicke, and Nigel G. Shrive. "Homo sapiens May Incorporate Daily Acute Cycles of “Conditioning–Deconditioning” to Maintain Musculoskeletal Integrity: Need to Integrate with Biological Clocks and Circadian Rhythm Mediators." International Journal of Molecular Sciences 23, no. 17 (September 1, 2022): 9949. http://dx.doi.org/10.3390/ijms23179949.
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Human evolution required adaptation to the boundary conditions of Earth, including 1 g gravity. The bipedal mobility of Homo sapiens in that gravitational field causes ground reaction force (GRF) loading of their lower extremities, influencing the integrity of the tissues of those extremities. However, humans usually experience such loading during the day and then a period of relative unloading at night. Many studies have indicated that loading of tissues and cells of the musculoskeletal (MSK) system can inhibit their responses to biological mediators such as cytokines and growth factors. Such findings raise the possibility that humans use such cycles of acute conditioning and deconditioning of the cells and tissues of the MSK system to elaborate critical mediators and responsiveness in parallel with these cycles, particularly involving GRF loading. However, humans also experience circadian rhythms with the levels of a number of mediators influenced by day/night cycles, as well as various levels of biological clocks. Thus, if responsiveness to MSK-generated mediators also occurs during the unloaded part of the daily cycle, that response must be integrated with circadian variations as well. Furthermore, it is also possible that responsiveness to circadian rhythm mediators may be regulated by MSK tissue loading. This review will examine evidence for the above scenario and postulate how interactions could be both regulated and studied, and how extension of the acute cycles biased towards deconditioning could lead to loss of tissue integrity.
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Liu, Lei, Xiao Zhang, Yu Feng Zhou, Xian Shuai Chen, and Ya Ling Wang. "Influence on Fatigue and Biomechanics of Cone Fit of Dental Implant around the Surrounding Bone Tissue." Materials Science Forum 872 (September 2016): 281–86. http://dx.doi.org/10.4028/www.scientific.net/msf.872.281.
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In this paper, the purpose is to compare three different cone fit of dental implant around the surrounding bone tissue that influence on fatigue and biomechanics, it is also to provide a theoretical basis for the design and clinical application of dental implant. The method is that loading the force 100N and 200N with different angle to the three different cone with dental implant with the finite element analysis (FEA) that analyzes the stress and fatigue in ideal conditions. The Results is that when the loading is vertical, cone for 3 degrees of the implant have the best performance. The cone for 80 degrees of the implant is min among the max equivalent stress of the implants. However, comprehensive view, Cone for 24 degrees of the implant the most stable. we find that cone of different implant when subjected to the same force the maximum equivalent stress is different, smaller conical implant under vertical load force have good performance, but with the increase of the loading angle the bigger conical implant performance better.
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Kairaitis, Kristina, Radha Parikh, Rosie Stavrinou, Sarah Garlick, Jason P. Kirkness, John R. Wheatley, and Terence C. Amis. "Upper airway extraluminal tissue pressure fluctuations during breathing in rabbits." Journal of Applied Physiology 95, no. 4 (October 2003): 1560–66. http://dx.doi.org/10.1152/japplphysiol.00432.2003.
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Transmural pressure at any level in the upper airway is dependent on the difference between intraluminal airway and extraluminal tissue pressure (ETP). We hypothesized that ETP would be influenced by topography, head and neck position, resistive loading, and stimulated breathing. Twenty-eight male, New Zealand White, anesthetized, spontaneously breathing rabbits breathed via a face mask with attached pneumotachograph to measure airflow and pressure transducer to monitor mask pressure. Tidal volume was measured via integration of the airflow signal. ETP was measured with a pressure transducer-tipped catheter inserted in the tissues of the lateral (ETPlat, n = 28) and anterior (ETPant, n = 21) pharyngeal wall. Head position was controlled at 30, 50, or 70°, and the effect of addition of an external resistor, brief occlusion, or stimulated breathing was examined. Mean ETPlat was ∼0.7 cmH2O greater than mean ETPant when adjusted for degree of head and neck flexion ( P < 0.05). Mean, maximum, and minimum ETP values increased significantly by 0.7-0.8 cmH2O/20° of head and neck flexion when adjusted for site of measurement ( P < 0.0001). The main effect of resistive loading and occlusion was an increase in the change in ETPlat (maximum - minimum ETPlat) and change in ETPant at all head and neck positions ( P < 0.05). Mean ETPlat and ETPant increased with increasing tidal volume at head and neck position of 30° (all P < 0.05). In conclusion, ETP was nonhomogeneously distributed around the upper airway and increased with both increasing head and neck flexion and increasing tidal volume. Brief airway occlusion increased the size of respiratory-related ETP fluctuations in upper airway ETP.
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Nakano, Takayoshi, Aira Matsugaki, Takuya Ishimoto, Mitsuharu Todai, Ai Serizawa, Ryoichi Suetoshi, Yoshihiro Noyama, and Wataru Fujitani. "Control of Oriented Extracellular Matrix Similar to Anisotropic Bone Microstructure." Materials Science Forum 783-786 (May 2014): 72–77. http://dx.doi.org/10.4028/www.scientific.net/msf.783-786.72.
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Bone microstructure is dominantly composed of anisotropic extracellular matrix (ECM) in which collagen fibers and epitaxially-oriented biological apatite (BAp) crystals are preferentially aligned depending on the bone anatomical position, resulting in exerting appropriate mechanical function. The regenerative bone in bony defects is however produced without the preferential alignment of collagen fibers and the c-axis of BAp crystals, and subsequently reproduced to recover toward intact alignment. Thus, it is necessary to produce the anisotropic bone-mimetic tissue for the quick recovery of original bone tissue and the related mechanical ability in the early stage of bone regeneration. Our group is focusing on the methodology for regulating the arrangement of bone cells, the following secretion of collagen and the self-assembled mineralization by oriented BAp crystallites. Cyclic stretching in vitro to bone cells, principal-stress loading in vivo on scaffolds, step formation by slip traces on Ti single crystal, surface modification by laser induced periodic surface structure (LIPSS), anisotropic collagen substrate with the different degree of orientation, etc. can dominate bone cell arrangement and lead to the construction of the oriented ECM similar to the bone tissue architecture. This suggests that stress/strain loading, surface topography and chemical anisotropy are useful to produce bone-like microstructure in order to promote the regeneration of anisotropic bone tissue and to understand the controlling parameters for anisotropic osteogenesis induction.
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Blangino, Eugenia, Martín A. Cagnoli, Ramiro M. Irastorza, and Fernando Vericat. "The Effect of Mechanical Constraints on Gelatin Samples under Pulsatile Flux." Materials Science Forum 706-709 (January 2012): 449–54. http://dx.doi.org/10.4028/www.scientific.net/msf.706-709.449.
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It is of great interest in tissue engineering the role of collagen gel-based structures (scaffolds, grafts and-by cell seeded and maturation-tissue equivalents (TEs) for several purposes). It is expected the appropriate biological compatibility when the extracellular matrix (ECM) is collagen-based. Regarding the mechanical properties (MP), great efforts in tissue engineering are focused in tailoring TE properties by controlling ECM composition and organization. When cells are seeded, the collagen network is remodeled by cell-driven compaction and consolidation, produced mainly through the mechanical stimuli that can be directed selecting the geometry and the surfaces exposed to the cells. Collagen gels have different (chemical and mechanical) properties depending on their origin and preparation conditions. The MP of the collagen network are derived from the degree of cross-linking (CLD) which can be modified by different treatments. One of the techniques to evaluate MP in the network is by ultrasound (US). In this work we analyse the effect of several mechanical constraints (similar to that imposed to promote cell growth on certain sample surfaces, when seeded) on samples of gelatin with a specific geometry (thick walls cylinders) under loading conditions of pulsatile flow. We checked US parameters and estimates evolution of the network structure for different restrictions in the sample mobility. It was implemented by adapting devices specially built to measure elastic properties of biological tissues by US. The material (origin and purity) and the preparation conditions for the gelatin were selected in order to compare the results with those of literature.
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Lisee, Caroline M., Alyssa Evans-Pickett, Hope Davis-Wilson, Lara Longobardi, Jason R. Franz, Amanda E. Munsch, and Brian Pietrosimone. "Association Between Biochemical Joint Tissue Response To Loading And Femoral Cartilage Composition After Knee Surgery." Medicine & Science in Sports & Exercise 54, no. 9S (September 2022): 106–7. http://dx.doi.org/10.1249/01.mss.0000876376.17913.ee.
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Best, Thomas M., Yi Zhao, Hechmi Toumi, and Scott K. Crawford. "Effects of Tissue Loading due to Massage on Muscle Mechanical Property Recovery Following Eccentric Exercise." Medicine & Science in Sports & Exercise 48 (May 2016): 590. http://dx.doi.org/10.1249/01.mss.0000486770.82785.e4.
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Michigami, Toshimi, Masanobu Kawai, Miwa Yamazaki, and Keiichi Ozono. "Phosphate as a Signaling Molecule and Its Sensing Mechanism." Physiological Reviews 98, no. 4 (October 1, 2018): 2317–48. http://dx.doi.org/10.1152/physrev.00022.2017.
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In mammals, phosphate balance is maintained by influx and efflux via the intestines, kidneys, bone, and soft tissue, which involves multiple sodium/phosphate (Na+/Pi) cotransporters, as well as regulation by several hormones. Alterations in the levels of extracellular phosphate exert effects on both skeletal and extra-skeletal tissues, and accumulating evidence has suggested that phosphate itself evokes signal transduction to regulate gene expression and cell behavior. Several in vitro studies have demonstrated that an elevation in extracellular Piactivates fibroblast growth factor receptor, Raf/MEK (mitogen-activated protein kinase/ERK kinase)/ERK (extracellular signal-regulated kinase) pathway and Akt pathway, which might involve the type III Na+/Picotransporter PiT-1. Excessive phosphate loading can lead to various harmful effects by accelerating ectopic calcification, enhancing oxidative stress, and dysregulating signal transduction. The responsiveness of mammalian cells to altered extracellular phosphate levels suggests that they may sense and adapt to phosphate availability, although the precise mechanism for phosphate sensing in mammals remains unclear. Unicellular organisms, such as bacteria and yeast, use some types of Pitransporters and other molecules, such as kinases, to sense the environmental Piavailability. Multicellular animals may need to integrate signals from various organs to sense the phosphate levels as a whole organism, similarly to higher plants. Clarification of the phosphate-sensing mechanism in humans may lead to the development of new therapeutic strategies to prevent and treat diseases caused by phosphate imbalance.
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Pieretti, Eurico F., Tomaz P. Leivas, Marina F. Pillis, and Mauricio David Martins das Neves. "Failure Analysis of Metallic Orthopedic Implant for Total Knee Replacement." Materials Science Forum 1012 (October 2020): 471–76. http://dx.doi.org/10.4028/www.scientific.net/msf.1012.471.
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Fractures resulting from wear and fatigue process have been identified as the main causes of failure in biomaterials, especially in implants that act in place of bone or other hard tissue, as they are subject to conditions involving severe cyclic loadings. In biomaterialscase, the types of failures mentioned above must also be evaluated under the effect of degradation or corrosion, due to the direct contact with body fluids. The present research analyzed the fatigue induced by corrosion fracture of an orthopaedic implant for total knee replacementproduced with an austenitic ASTM F138 stainless steel. The morphology, compositions of the interfaces and subsequent corrosive pitting were characterized by stereoscopy and scanning electron microscopy (SEM) coupled with energy dispersive spectroscopy (EDS). Stress concentration, inclusions and high carbon levels were the main reasons of failure.
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Valiev, Ruslan, Irina P. Semenova, Enja Jakushina, V. V. Latysh, Henry J. Rack, Terry C. Lowe, Jiri Petruželka, L. Dluhoš, D. Hrušák, and J. Sochová. "Nanostructured SPD Processed Titanium for Medical Implants." Materials Science Forum 584-586 (June 2008): 49–54. http://dx.doi.org/10.4028/www.scientific.net/msf.584-586.49.
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Nanostructured titanium (nTi) with essential enhanced strength and fatigue characteristics is an advanced material for dental implant applications. Nano Ti is commercially pure titanium, that was nanostructured by a special technique of severe plastic deformation. It is bio inert, does not contain even potentially toxic or allergenetic additives and has significantly higher specific strength properties than any other titanium applied in dental implants. Cylindrical threaded screw implants Nanoimplant® sized 2.4 mm in diameter and 12 mm in length were made from nTi. It is the first application of nTi dental implant in the world reported. Recently more than 250 successful clinical applications dealing with surgery on the front teeth were carried out. No complications were noticed during the early postoperative period and early loading. Laboratory cytocompatibility tests undertaken so far on mice fibroblast cells have indicated that nanocrystalline Ti surface has a significantly better property for cell colonisation and healing of tissue consequently.
Conference papers on the topic "MSK Tissue Loading"
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Baker, Brendon M., Roshan P. Shah, and Robert L. Mauck. "Dynamic Tensile Loading Improves the Mechanical Properties of MSC-Laden Aligned Nanofibrous Scaffolds." In ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19447.
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Fibrocartilaginous tissues such as the meniscus and annulus fibrosus serve critical load-bearing roles, relying on arrays of highly organized collagen fibers to resist tensile loads experienced with normal physiologic activities [1]. As these specialized structures are often injured, there exists great demand for engineered tissues for repair or replacement. Towards recreating the structural and mechanical features of these anisotropic tissues in vitro, we fabricate scaffolds composed of co-aligned, ultra-fine biodegradable polymer fibers. These 3D micro-patterns direct mesenchymal stem cell (MSC) orientation and the subsequent formation of organized extracellular matrix (ECM) [2]. As this cell-produced matrix continually develops with time in culture, the mechanical properties of the construct gradually increase. In previous studies aimed at engineering human meniscus tissue, constructs achieved moduli of ∼40MPa after 10 weeks of culture, representing a two-fold increase in the starting properties of the scaffold [3]. Despite this demonstrable increase, this value remains well below that of the native tissue. As mechanical forces are essential to the maintenance of musculoskeletal tissues, this work examined the effect of cyclic tensile loading on MSC-laden nanofibrous constructs to enhance their in vitro maturation. We hypothesized that this loading modality would modulate the transcriptional behavior of seeded MSCs, spur the deposition of collagen-rich matrix, and lead to additional improvements in construct mechanical properties.
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Huang, Alice H., Brendon M. Baker, Gerard A. Ateshian, and Robert L. Mauck. "Sliding Contact Loading Improves the Tensile Properties of MSC-Based Engineered Cartilage." In ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19292.
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Articular cartilage is a load-bearing surface whose mechanical function arises from its unique properties. The structural and mechanical properties of mature cartilage are inhomogeneous through the depth and anisotropic. Tissue maturation is directed by mechanical forces; loading induces remodeling of the immature matrix, leading to increases in compressive and tensile properties and the development of tissue anisotropy [1, 2]. Limitations in cartilage repair strategies have engendered numerous efforts to engineer functional replacements. As mesenchymal stem cells (MSCs) undergo chondrogenesis in 3D culture, this cell type has been increasingly utilized in these efforts [3]. Despite their initial promise however, generating MSC-based constructs with the mechanical complexity and integrity of cartilage remains a challenge; the properties of MSC-seeded hydrogels are consistently lower than those of the native tissue [4, 5]. As mechanical stimulation is critical to cartilage development and maturation, bioreactor systems that simulate the native mechanical environment of cartilage may bridge these functional disparities. Indeed, dynamic axial compression enhances the compressive properties of both chondrocyte- and MSC-based engineered cartilage, though collagen content remains low [6, 7]. While promising, these studies were not designed to generate either depth-dependence or constructs with improved tensile properties. We therefore developed a new sliding contact bioreactor system that can better recapitulate the mechanical stimuli arising from joint motion (two contacting cartilage layers). In previous experiments using this system, we demonstrated improved expression of chondrogenic genes with short-term sliding contact of MSC-seeded agarose; these changes in gene expression were dependent on both axial strain and TGF-β supplementation [8]. Furthermore, FEM analysis of sliding contact showed that tensile strains (parallel to the sliding direction) and fluid efflux/influx were depth-dependent and highest in the region closest to the construct surface [8]. In the current study, we applied long-term sliding contact to MSC-seeded agarose constructs using the optimized parameters previously determined. We hypothesized that sliding contact would improve tensile properties and direct depth-dependent matrix remodeling.
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Paiva, Gavin, and Trent Guess. "Development of Generalized Parameters for Canine Multibody Meniscus Models From Experimental Data." In ASME 2011 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2011. http://dx.doi.org/10.1115/sbc2011-53617.
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It has been established that in order to accurately model a knee joint a reasonable approximation of the soft tissues present is necessary1. Models which include these soft tissue structures are able to better reproduce joint kinematics, loading, and analyze the impact of damage and pathological joint behavior1. Simulating the behavior of these tissues requires either a detailed understanding of materials properties that can be implemented via finite element models or the production of an empirical model that can be implemented inside other model frameworks2,3. This study explores the application of multibody (MB) modeling techniques in an attempt to capture the flexible behavior of biological tissues inside of a rigid body mechanics software, MD ADAMS (MSC software, Santa Ana, California), by tuning the performance to experimental data using design of experiments (DOE).
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Huang, Alice H., and Robert L. Mauck. "Repeated Dynamic Loading Modulates Cartilage Gene Expression but Does Not Improve Mechanical Properties of MSC-Laden Hydrogels." In ASME 2009 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2009. http://dx.doi.org/10.1115/sbc2009-204339.
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Mesenchymal stem cells (MSCs) are a multi-potential cell type that can differentiate toward a variety of tissue-specific phenotypes, including cartilage. Given their chondrogenic potential, MSCs are a promising cell source for cartilage tissue engineering (TE). However, while MSCs readily undergo chondrogenesis in 3D culture and deposit a cartilage-like matrix, the mechanical properties of MSC-seeded constructs are greatly inferior to chondrocyte-seeded constructs similarly maintained [1]. To date, optimization strategies for enhancing functional MSC chondrogenesis, including increasing seeding density and transient application of growth factor, have shown limited success [3]. Using microarray analysis, we have recently demonstrated that mis-expression of certain genes, including lubricin, chondromodulin and RGD-CAP, a collagen associated protein, may underlie this disparity in mechanical function [2]. In this study, we examined dynamic compression as an alternative method to enhance MSC differentiation. Previous work using chondrocyte-based constructs have demonstrated that matrix biosynthesis and mechanical properties were improved with the application of cyclic compression [4]. Furthermore, upregulation of lubricin was observed when surface motion was applied to chondrocyte-seeded porous scaffolds [5]. While significant effort has gone toward optimizing loading parameters to direct tissue growth of chondrocyte-based constructs, few studies have examined the effects of mechanical stimulation on MSC-based constructs. Some have demonstrated positive effects on MSC chondrogenesis with application of compressive loading [6, 7], while others have shown that long-term loading may adversely affect the developing mechanical properties of MSC-seeded constructs [8]. In this study, we examined the effects of repeated dynamic compressive loading on MSC chondrogenesis and showed that mechanical properties and gene expression were modulated by this loading modality.
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Metzger, Thomas A., Stephen A. Schwaner, and Glen L. Niebur. "Pressure Gradients in the Trabecular Pore Space of Femurs During Physiologic Loading." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14433.
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Bone marrow is an important niche for mesenchymal stromal cells (MSCs), which are progenitors for connective tissue cells. MSCs respond to mechanical stimuli (1). For example, steady and oscillatory fluid flow both affect MSC differentiation to the osteogenic lineages (2), while hydrostatic pressure increases MSC osteogenic protein expression (3). Both pressure and fluid flow are induced in bone marrow during loading due to the poroelastic nature of trabecular bone, and these may affect the differentiation or proliferation of the resident stromal cells.
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Nathan, Ashwin S., Brendon M. Baker, and Robert L. Mauck. "Cytoskeletal Control of Mesenchymal Stem Cell Nuclear Deformation on Nanofibrous Scaffolds." In ASME 2009 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2009. http://dx.doi.org/10.1115/sbc2009-206855.
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Nanofibrous scaffolds hold great potential for tissue engineering as they recapitulate the mechanical and topographic features of fibrous tissues on both the macroscopic and microscopic level [1,2]. When seeded with cells capable of fibrous extracellular matrix (ECM) production such as mesenchymal stem cells (MSCs), the new matrix is deposited in accordance with the underlying topography, and scaffolds develop improved mechanical properties with time in free swelling culture [6]. While promising, the free swelling conditions employed in evaluating in vitro construct maturation have thus far remained insufficient in achieving native-level properties. As most fibrous tissues are subjected to loading in vivo, mechanical conditioning is considered critical in directing tissue development and subsequent homeostasis with normal use. Mechanical signals are translated from the ECM to the nucleus via the cytoskeleton, with signals culminating in the control of biosynthetic activity based upon external loading conditions. Various bioreactor systems have been developed to mimic these in vivo conditions towards enhancing the maturation of engineered constructs, with most focusing on dynamic tensile deformation [3,4]. Towards gaining further insight into the means by which mechanical cues inspire alterations in cellular behavior, this study developed methods for evaluating cell and sub-cellular deformation of MSCs seeded on randomly-oriented and aligned nanofibrous scaffolds. Using a device that enables visualization of cells seeded on nanofibrous scaffolds undergoing static tensile deformation, we examined the effect of applied strain rate on cell adhesion to scaffolds, as well as changes in nuclear shape in the context of viable actin and microtubule sub-cellular networks with applied strain. These data provide new insight into fundamental mechanisms of MSC mechanoregulation on nanofibrous scaffolds, and offer constraints for long-term bioreactor studies.
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Hu, M., R. Yeh, M. Lien, and Y. X. Qin. "In Vivo Mesenchymal Stem Cell Proliferation in Response to Dynamic Fluid Flow Stimulation." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80586.
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Osteoporosis is a debilitating disease characterized as decreased bone mass and structural deterioration of bone tissue. Osteoporotic bone tissue turns itself into altered structure, which leads to weaker bones that are more susceptible for fractures. While often happening in elderly, long-term bed-rest patients, e.g. spinal cord injury, and astronauts who participate in long-duration spaceflights, osteoporosis has been considered as a major public health thread and causes great medical cost impacts to the society. Mechanobiology and novel stimulation on regulating bone health have long been recognized. Loading induced bone fluid flow, as a critical mechanotransductive promoter, has been demonstrated to regulate cellular signaling, osteogenesis, and bone adaptation [4]. As one of the factors that mediate bone fluid flow, intromedullary pressure (ImP) creates a pressure gradient that further influence the magnitude of mechanotransductory signals [5]. As for a potential translational development of ImP, our group has recently introduced a novel, non-invasive dynamic hydraulic stimulation (DHS) on bone structural enhancement. Its promising effects on inhibition of disuse bone loss has been shown with 2 Hz loading through a 4-week hindlimb suspension rat study followed by microCT analysis. At the cellular level, mesenchymal stem cells (MSCs) are defined by their self-renewal ability and that to potentially differentiate into the cells that form tissues such as bone [1]. To further elucidate the cellular effects of DHS and its potential mechanism on bone quality enhancement, the objective of this study was to measure MSC quantification in response to the in vivo mechanical signals driven by DHS.
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Heo, Su-Jin, Tristan P. Driscoll, and Robert L. Mauck. "Dynamic Tensile Loading Activates TGF and BMP Signaling in Mesenchymal Stem Cells on Aligned Nanofibrous Scaffolds." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80706.
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Mesenchymal stem cells (MSCs) are a promising cell source for tissue engineering applications, given their ease of isolation and multi-potential differentiation capacity [1]. External mechanical cues directly influence MSC lineage commitment [2]. However, it is not yet clear how these physical cues are transduced to the cell nucleus, an understanding of which may prove essential for orthopaedic tissue engineering. Transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP), members of the TGF beta superfamily, regulate cellular processes including growth and differentiation [3, 4]. TGF and/or BMP ligand binding initiate SMAD phosphorylation, translocation to the nucleus, and transcriptional activation of target genes [4]. Additionally, both ligands can influence the organization of chromatin and the Lamin A/C (LMAC) nucleoskeletal network [5]. For example, we have recently shown that TGF-β3 leads to corticalized LMAC, marked increases in heterochromatin (HTC), and increased nuclear stiffness [6]. Interestingly, dynamic tensile stretch of MSCs on aligned nanofibrous scaffolds, in the absence of these differentiation factors, resulted in many of these same nuclear transformations [6, 7]. The objective of this study was to identify how dynamic tensile stress is transduced in MSCs on aligned nanofibrous scaffolds, and further, to ascertain whether these mechanoregulatory changes are coordinated through TGFβ/BMP signaling pathways.
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Farrell, Megan J., Tiffany L. Zachry, and Robert L. Mauck. "Micromechanical Deformation of Chondrogenic Mesenchymal Stem Cells in 3D Hydrogels is Modulated by Time in Culture and Matrix Connectivity." In ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19534.
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Mesenchymal stem cells (MSCs) are a clinically attractive alternative to chondrocytes for the development of engineered cartilage tissue owing to their ease of isolation and chondrogenic potential [1]. However, the mechanical properties of MSC-based constructs have yet to match those of native cartilage or of chondrocyte-based constructs cultured similarly [1]. One route for improving these properties may be the application of mechanical stimulation, as normal cartilage development and homeostatic maintenance is dependent on force transduction. In a tissue engineering context, dynamic compression applied to chondrocyte-seeded hydrogels modulates both matrix production and mechanical properties [2, 3]. Similarly, when MSCs are embedded in 3D hydrogels, expression of chondrogenic markers and cartilaginous ECM synthesis are differentially regulated by dynamic compressive loading [4, 5]. Indeed, we have recently shown that long-term dynamic loading initiated after a pre-culture period of 21 days in pro-chondrogenic medium improves matrix distribution and the compressive properties of MSC-seeded constructs [5]. Interestingly, when loading was initiated after a single day of culture, mechanical properties failed to develop [6, 7], suggesting that elaboration of matrix was required prior to dynamic loading in order to positively direct construct maturation. When chondrocytes are embedded in agarose, the initial growth phase is characterized by the establishment of a dense pericellular matrix (PCM). At early times in culture, before these islands of PCM become connected into an interterritorial matrix, cells are protected from bulk deformation applied to the gel [8]. In a recent study, we showed that clonal heterogeneity in stem cell populations determines the rate at which this PCM forms, with some MSC clones rapidly establishing a dense PCM, while others fail to develop a robust PCM (and so continue to deform with gel deformation) through several weeks in culture [9]. To further this investigation, this study charted the culture time-dependent changes in ECM connectivity and MSC deformation under basal and chondrogenic conditions.
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Heo, Su-Jin, Nandan L. Nerurkar, Tristan P. Driscoll, and Robert L. Mauck. "Differentiation and Dynamic Tensile Loading Alter Nuclear Mechanics and Mechanoreception in Mesenchymal Stem Cells." In ASME 2011 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2011. http://dx.doi.org/10.1115/sbc2011-53432.
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Mesenchymal stem cells (MSCs) are a promising cell source for tissue engineering applications, given their ease of isolation and multi-potential differentiation capacity [1]. Passive and active mechanical signals can direct MSC lineage commitment [2], however, the subcellular machinery that translates physical cues to biologic response remains unclear. Direct deformation of the nucleus may influence differentiation by inducing mechanical reorganization of nuclear chromatin. Because the nuclei of differentiated cells are stiffer than progenitor cells [3], it is possible that such mechanoregulatory mechanisms vary with differentiation state. Lamin A/C is a filamentous protein that largely defines nuclear shape, size and stiffness [3]. Recent work suggests that Lamin A/C also regulates chromatin organization and transcriptional activity [4]. Recently, we have developed an in vitro system to direct the functional differentiation of MSCs into fibrochondrocytes, using electrospun polymeric nanofiber substrates [5]. Alignment of nanofibers directs cell alignment, allowing external forces to be applied uniformly along the long axes of cells, emulating the mechanical microenvironment experienced by embryonic progenitors during fibrous tissue morphogenesis [6]. We have noted, however, that as MSCs undergo fibrochondrogenesis, translation of scaffold deformation to nuclear deformation is attenuated [7]. From those studies, it was not clear whether this was due to changes in cellular mechanics or to accretion of extracellular matrix during differentiation. Thus the objective of the present work was to specifically identify how fibrochondrogenesis of MSCs on aligned nanofibrous scaffolds alters nuclear mechanics and mechanoreception, and further to ascertain whether mechanical stimulation alone can elicit similar mechanoregulatory changes.