Creating stiffness gradient polyvinyl alcohol hydrogel using a simple gradual freezing–thawing method to investigate stem cell differentiation behaviors

Kim, Tae Ho; An, Dan Bi; Oh, Se Heang; Kang, Min Woo; Song, Hyun Hoon; Lee, Jin Ho

doi:10.1016/j.biomaterials.2014.11.017

Cited by 197 publications

(126 citation statements)

References 48 publications

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“…1c) have added further pieces to our most accurate models of in vivo stiffness conditions. Controlling stiffness gradients in spatial planes has been accomplished with a variety of methods, including repeated freeze-thaw cycles with liquid nitrogen and cylindrical polyvinyl alcohol columns [42], heat gradients within polymerizing polydimethylsiloxane [37], polyelectrolyte monolayers with patterned cross-linker [43], inclusion of rigid particles in a soft hydrogel [44], and microfluidic mixing of different polyacrylamide (PA) solutions. Still other methods have employed photo-initiators and a patterned [40, 45, 46] or moving [47–49] photomask overlying a polymerization chamber to create stiffness gradients.…”

Section: The Physical Worldmentioning

confidence: 99%

The extracellular microscape governs mesenchymal stem cell fate

Hadden

Choi

2016

J Biol Eng

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Each cell forever interacts with its extracellular matrix (ECM); a stem cell relies on this interaction to guide differentiation. The stiffness, nanotopography, protein composition, stress and strain inherent to any given ECM influences stem cell lineage commitment. This interaction is dynamic, multidimensional and reciprocally evolving through time, and from this concerted exchange the macroscopic tissues that comprise living organisms are formed. Mesenchymal stem cells can give rise to bone, cartilage, tendon and muscle; thus attempts to manipulate their differentiation must heed the physical properties of incredibly complex native microenvironments to realize regenerative goals.

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Section: The Physical Worldmentioning

confidence: 99%

The extracellular microscape governs mesenchymal stem cell fate

Hadden

Choi

2016

J Biol Eng

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“…To create stiffness gradients in vitro, a multitude of diverse methods have been proposed, including repeated freeze-thaw methods with liquid nitrogen and cylindrical polyvinyl alcohol columns (25), heat gradients within polymerizing polydimethylsiloxane (PDMS) (10), polyelectrolyte monolayers with a patterned crosslinker (26), inclusion of rigid particles in a soft hydrogel (27), and microfluidic mixing of different polyacrylamide (PA) solutions. However, all require significant technical background or equipment or are exceedingly expensive.…”

mentioning

confidence: 99%

Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels

Hadden

Young

Holle

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

410

323

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The spatial presentation of mechanical information is a key parameter for cell behavior. We have developed a method of polymerization control in which the differential diffusion distance of unreacted cross-linker and monomer into a prepolymerized hydrogel sink results in a tunable stiffness gradient at the cell-matrix interface. This simple, low-cost, robust method was used to produce polyacrylamide hydrogels with stiffness gradients of 0.5, 1.7, 2.9, 4.5, 6.8, and 8.2 kPa/mm, spanning the in vivo physiological and pathological mechanical landscape. Importantly, three of these gradients were found to be nondurotactic for human adipose-derived stem cells (hASCs), allowing the presentation of a continuous range of stiffnesses in a single well without the confounding effect of differential cell migration. Using these nondurotactic gradient gels, stiffness-dependent hASC morphology, migration, and differentiation were studied. Finally, the mechanosensitive proteins YAP, Lamin A/C, Lamin B, MRTF-A, and MRTF-B were analyzed on these gradients, providing higher-resolution data on stiffness-dependent expression and localization. mechanobiology | stem cell migration | stem cell differentiation | extracellular matrix | stiffness

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“…The seeded RAW 264.7 macrophages were preferentially located on stiffer regions of the hydrogel. Very recently, Lee et al [79] investigated the cell behavior on the stiffness gradient PVA hydrogel. In this work, the hydrogel region with low stiffness (~1 kPa) was favorable to TUJ1 expression (for neurogenesis), while the hydrogel region with high stiffness (~24 kPa) was favorable to osteopontin expression (for osteogenesis).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

“…Moreover, the toxicity is inevitably introduced during the fabrication process from the residual monomers, initiators and cross-linkers [77,78]. Recently, Lee and coworkers reported on the fabrication of cylindrical polyvinyl alcohol (PVA) hydrogel with a stiffness gradient by using liquid nitrogen contacting method from a gradual freezing and thawing process [79]. The as-prepared gradient PVA hydrogel remained nontoxic [80].…”

Section: A N U S C R I P Tmentioning

confidence: 99%

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Structural hydrogels

Pei

et al. 2016

Polymer

119

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Structural hydrogels by different methods with diversified geometric shapes and dimensions, have been of wide interest over few decades due to great potential applications in tissue engineering, drug release, actuation and sensation.Abstract: Research on hydrogel systems with structural features has aroused great interests due to its wide range of applications, including actuators, microfluidic units, synthetic adhesives, transplantable tissue organs, and cell scaffolds. This review article describes, with special emphasis, the design and fabrication of structural hydrogels with diversified geometric shapes and dimensions. These hydrogel structures include gradient gel, anisotropic gel, gel patterns, gel wrinkle, gel arrays and gel tubes. Several typical applications of such structural hydrogels are introduced, such as for controlling cell behavior, developing responsive actuators, and designing nature inspired bio-lubrication surface. Some perspectives on future development of structural hydrogel systems are provided.

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Creating stiffness gradient polyvinyl alcohol hydrogel using a simple gradual freezing–thawing method to investigate stem cell differentiation behaviors

Cited by 197 publications

References 48 publications

The extracellular microscape governs mesenchymal stem cell fate

The extracellular microscape governs mesenchymal stem cell fate

Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels

Structural hydrogels

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