A combination of shear and dynamic compression leads to mechanically induced chondrogenesis of human mesenchymal stem cells

Schätti, O.R.; Grad, Sibylle; Goldhahn, Jörg; Salzmann, Gian M.; Li, Z; Alini, Mauro; Stoddart, M J

doi:10.22203/ecm.v022a17

Cited by 164 publications

(178 citation statements)

References 25 publications

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“…Sliding will result in uneven and inconsistent shear loading of the specimen. Newer bioreactors, such as the unique "rolling ball" system 22,23 and a biaxial stimulation device 16 , create a much more realistic and consistent loading environment; however, they only allow one sample to be loaded at a time. Large sample sizes are essential for performing the necessary biochemical, mechanical, and histological analyses on the constructs with a high level of confidence.…”

Section: Discussionmentioning

confidence: 99%

Design of a Biaxial Mechanical Loading Bioreactor for Tissue Engineering

Bilgen

Chu

Stefani

et al. 2013

JoVE

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We designed a loading device that is capable of applying uniaxial or biaxial mechanical strain to a tissue engineered biocomposites fabricated for transplantation. While the device primarily functions as a bioreactor that mimics the native mechanical strains, it is also outfitted with a load cell for providing force feedback or mechanical testing of the constructs. The device subjects engineered cartilage constructs to biaxial mechanical loading with great precision of loading dose (amplitude and frequency) and is compact enough to fit inside a standard tissue culture incubator. It loads samples directly in a tissue culture plate, and multiple plate sizes are compatible with the system. The device has been designed using components manufactured for precision-guided laser applications. Bi-axial loading is accomplished by two orthogonal stages. The stages have a 50 mm travel range and are driven independently by stepper motor actuators, controlled by a closed-loop stepper motor driver that features micro-stepping capabilities, enabling step sizes of less than 50 nm. A polysulfone loading platen is coupled to the bi-axial moving platform. Movements of the stages are controlled by Thor-labs Advanced Positioning Technology (APT) software. The stepper motor driver is used with the software to adjust load parameters of frequency and amplitude of both shear and compression independently and simultaneously. Positional feedback is provided by linear optical encoders that have a bidirectional repeatability of 0.1 μm and a resolution of 20 nm, translating to a positional accuracy of less than 3 μm over the full 50 mm of travel. These encoders provide the necessary position feedback to the drive electronics to ensure true nanopositioning capabilities. In order to provide the force feedback to detect contact and evaluate loading responses, a precision miniature load cell is positioned between the loading platen and the moving platform. The load cell has high accuracies of 0.15% to 0.25% full scale. Video LinkThe video component of this article can be found at

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Section: Discussionmentioning

confidence: 99%

Design of a Biaxial Mechanical Loading Bioreactor for Tissue Engineering

Bilgen

Chu

Stefani

et al. 2013

JoVE

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“…We hypothesize that by quantifying various measures of mechanical stimuli within hMSCenriched fibrin-polyurethane composite scaffolds using the FE modeling and by correlating the quantitative FE results with the findings of dynamic in vitro experiments, previously published by Schätti et al, 35 it is possible to further elucidate the mechanoregulation of chondrogenesis in tissueengineered constructs.…”

Section: Introductionmentioning

confidence: 98%

“…33,34 In this context, Schätti et al further explored the influence of sliding contact on human MSC (hMSC)-enriched fibrinpolyurethane composite scaffolds by applying compression and interfacial shear loads separately and concluded that either compression or interfacial shear alone was insufficient for the chondrogenic induction of hMSCs. 35 However, the application of interfacial shear superimposed upon dynamic compression led to significant increases in chondrogenic gene expression and proteoglycan-rich extracellular matrix (ECM). 35 Nevertheless, despite the fact that these studies provide clear evidence on the important role of mechanical stimulation for chondrogenic induction of MSCs, discrepancies exist among the results of in vitro studies in terms of MSCs response to mechanical loading.…”

Section: Introductionmentioning

confidence: 99%

“…35 However, the application of interfacial shear superimposed upon dynamic compression led to significant increases in chondrogenic gene expression and proteoglycan-rich extracellular matrix (ECM). 35 Nevertheless, despite the fact that these studies provide clear evidence on the important role of mechanical stimulation for chondrogenic induction of MSCs, discrepancies exist among the results of in vitro studies in terms of MSCs response to mechanical loading. One of the reasons for these inconsistencies is the fact that the mechanical stimuli within the constructs have been rarely quantified in these studies, whereas cells within the constructs can experience significantly discrepant types and levels of mechanical signals arising from the disparity among the loading protocols, the type of biomaterials, the geometry of the constructs, and the bioreactor design.…”

Section: Introductionmentioning

confidence: 99%

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Deciphering Mechanical Regulation of Chondrogenesis in Fibrin–Polyurethane Composite Scaffolds Enriched with Human Mesenchymal Stem Cells: A Dual Computational and Experimental Approach

Zahedmanesh

Stoddart

Lezuo

et al. 2014

Tissue Engineering Part A

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Fibrin-polyurethane composite scaffolds support chondrogenesis of human mesenchymal stem cells (hMSCs) derived from bone marrow and due to their robust mechanical properties allow mechanical loading in dynamic bioreactors, which has been shown to increase the chondrogenic differentiation of MSCs through the transforming growth factor beta pathway. The aim of this study was to use the finite element method, mechanical testing, and dynamic in vitro cell culture experiments on hMSC-enriched fibrin-polyurethane composite scaffolds to quantitatively decipher the mechanoregulation of chondrogenesis within these constructs. The study identified compressive principal strains as the key regulator of chondrogenesis in the constructs. Although dynamic uniaxial compression did not induce chondrogenesis, multiaxial loading by combined application of dynamic compression and interfacial shear induced significant chondrogenesis at locations where all the three principal strains were compressive and had a minimum magnitude of 10%. In contrast, no direct correlation was identified between the level of pore fluid velocity and chondrogenesis. Due to the high permeability of the constructs, the pore fluid pressures could not be increased sufficiently by mechanical loading, and instead, chondrogenesis was induced by triaxial compressive deformations of the matrix with a minimum magnitude of 10%. Thus, it can be concluded that dynamic triaxial compressive deformations of the matrix is sufficient to induce chondrogenesis in a thresholddependent manner, even where the pore fluid pressure is negligible.

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“…17). 105 Their results showed a significant increase in GAG production over a 3-week period when samples experienced both compressive and shear forces. Other strategies used to exert mechanical forces on cells include dynamic stamp, centrifugal forces, 106 and the use of hydrostatic pressure to apply cyclic compressive forces on stem cells.…”

Section: Synthesis Of Magneto-responsive Biomaterialsmentioning

confidence: 95%

Development of injectable, stimuli-responsive biomaterials as active scaffolds for applications in advanced drug delivery and osteochondral tissue regeneration

Adedoyin¹

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AcknowledgmentsFirst and foremost, I would like to thank my parents, Dr. John Akintayo Adedoyin and Dr.Omobola Adedoyin for their unconditional love, support and prayers. To my brothers, Dr.Ayodeji Adedoyin, and Mr. Akinola Adedoyin, thank you for your constant encouragement and advice. I owe much appreciation to my current and past lab mates -Meryem, Nandita, Ninad, Wei, Ted, Yang, Yue and Cristian. It has been a pleasure to work alongside you.To all my friends and adopted family at Northeastern, thank you for making my time here enjoyable and filled with wonderful memories. I would like to thank members of the Sridhar lab, specifically Dr. Rajiv Kumar, Codi Gharagouzloo, Bryce Delgado and Muizz Zaman, for their work in helping me with the synthesis and functionalization of the magnetic nanoparticles, developing the mathematical model of the force distribution within the nanocomposite scaffold, and the in vitro sustained drug release studies from the hydrogel that was done in collaboration with their lab. To my advisor, Dr. Adam K.Ekenseair, thank you for your leadership, wisdom and support during the past four and a half years. I also would like to thank my committee members, namely, Dr. Arthur Coury, Dr. Abigail Koppes, and Dr. Srinivas Sridhar for their guidance and mentorship. Lastly, thanks to the Chemical Engineering Community at NEU, without your support, none of this work would be possible. 3 AbstractOsteoarthritis (OA) is a degenerative joint disease that occurs when the cartilage matrix begins to breakdown. Every year, over 3.1 million surgeries are performed in an effort to treat damaged cartilage tissue. 4 Current treatment options such as osteochondral tissue grafting, micro-fracturing, and total knee replacements (TKRs) are effective in alleviating symptoms associated with OA, but often fail to promote the regeneration of normal cartilage. Therefore, due to the limitations of the current treatment options available, it has become necessary to develop better medical solutions to restore or regenerate cartilage tissue previously damaged by OA.Stimuli-responsive hydrogels, capable of exhibiting dramatic changes in swelling behavior, network structure, permeability and mechanical strength in response to changes in their local environment, have emerged as potential candidates as active scaffolds for several tissue engineering applications. Magneto-responsive biomaterials have become a subject of interest in the field of tissue engineering as their physical and structural properties could be manipulated spatiotemporally by varying the magnetic field strength, making them useful for applications in advanced drug delivery and osteochondral tissue regeneration. Thus, the goal of this thesis was to investigate the feasibility of developing an injectable, magneto-responsive hydrogel scaffold capable of delivering viable stem cell populations to a cartilage defect, and to spatiotemporally control the regeneration of the cartilage tissue in vivo.A magneto-responsive biomaterial was made by adding functional pa...

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A combination of shear and dynamic compression leads to mechanically induced chondrogenesis of human mesenchymal stem cells

Cited by 164 publications

References 25 publications

Design of a Biaxial Mechanical Loading Bioreactor for Tissue Engineering

Design of a Biaxial Mechanical Loading Bioreactor for Tissue Engineering

Deciphering Mechanical Regulation of Chondrogenesis in Fibrin–Polyurethane Composite Scaffolds Enriched with Human Mesenchymal Stem Cells: A Dual Computational and Experimental Approach

Development of injectable, stimuli-responsive biomaterials as active scaffolds for applications in advanced drug delivery and osteochondral tissue regeneration

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