Mechanical Properties of Cellularly Responsive Hydrogels and Their Experimental Determination

Kloxin, April M.; Kloxin, Christopher J.; Bowman, Christopher N.; Anseth, Kristi S.

doi:10.1002/adma.200904179

Cited by 428 publications

(381 citation statements)

References 116 publications

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“…Results shown in Figure 7 indicate that gelation begins immediately on exposure to light as seen in the rise in modulus. The cross over point of G 0 and G 00 , which is often used to estimate the gel point of the reaction, 41 occurred within the first few seconds of UV light exposure, which further emphasises …”

Section: Rheologymentioning

confidence: 99%

Poly(vinyl alcohol)-heparin biosynthetic microspheres produced by microfluidics and ultraviolet photopolymerisation

et al. 2013

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Biosynthetic microspheres have the potential to address some of the limitations in cell microencapsulation; however, the generation of biosynthetic hydrogel microspheres has not been investigated or applied to cell encapsulation. Droplet microfluidics has the potential to produce more uniform microspheres under conditions compatible with cell encapsulation. Therefore, the aim of this study was to understand the effect of process parameters on biosynthetic microsphere formation, size, and morphology with a co-flow microfluidic method. Poly(vinyl alcohol) (PVA), a synthetic hydrogel and heparin, a glycosaminoglycan were chosen as the hydrogels for this study. A capillary-based microfluidic droplet generation device was used, and by varying the flow rates of both the polymer and oil phases, the viscosity of the continuous oil phase, and the interfacial surface tension, monodisperse spheres were produced from $200 to 800 lm. The size and morphology were unaffected by the addition of heparin. The modulus of spheres was 397 and 335 kPa for PVA and PVA/heparin, respectively, and this was not different from the bulk gel modulus (312 and 365 for PVA and PVA/heparin, respectively). Mammalian cells encapsulated in the spheres had over 90% viability after 24 h in both PVA and PVA/heparin microspheres. After 28 days, viability was still over 90% for PVA-heparin spheres and was significantly higher than in PVA only spheres. The use of biosynthetic hydrogels with microfluidic and UV polymerisation methods offers an improved approach to long-term cell encapsulation. V C 2013 AIP Publishing LLC. [http://dx

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Section: Rheologymentioning

confidence: 99%

Poly(vinyl alcohol)-heparin biosynthetic microspheres produced by microfluidics and ultraviolet photopolymerisation

et al. 2013

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“…PEG-peptide hydrogels | human mesenchymal stem cells | cell migration | microrheology S ynthetic hydrogel scaffolds have been designed to serve as mimics of the native extracellular matrix (ECM) with the goal of promoting desired cell functions (e.g., proliferation, migration, differentiation), especially for applications in wound healing (1), tissue regeneration (2), and stem cell culture (3,4). For example, poly (ethylene glycol) (PEG) hydrogels can serve as blank slates in which peptide cues can be systematically introduced in the scaffold to allow integrin binding (5,6), proteolytic degradation (7,8), and even local sequestering of growth factors (9).…”

mentioning

confidence: 99%

Measuring dynamic cell–material interactions and remodeling during 3D human mesenchymal stem cell migration in hydrogels

Schultz

Kyburz

Anseth

2015

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

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165

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Biomaterials that mimic aspects of the extracellular matrix by presenting a 3D microenvironment that cells can locally degrade and remodel are finding increased applications as wound-healing matrices, tissue engineering scaffolds, and even substrates for stem cell expansion. In vivo, cells do not simply reside in a static microenvironment, but instead, they dynamically reengineer their surroundings. For example, cells secrete proteases that degrade extracellular components, attach to the matrix through adhesive sites, and can exert traction forces on the local matrix, causing its spatial reorganization. Although biomaterials scaffolds provide initially well-defined microenvironments for 3D culture of cells, less is known about the changes that occur over time, especially local matrix remodeling that can play an integral role in directing cell behavior. Here, we use microrheology as a quantitative tool to characterize dynamic cellular remodeling of peptide-functionalized poly(ethylene glycol) (PEG) hydrogels that degrade in response to cell-secreted matrix metalloproteinases (MMPs). This technique allows measurement of spatial changes in material properties during migration of encapsulated cells and has a sensitivity that identifies regions where cells simply adhere to the matrix, as well as the extent of local cell remodeling of the material through MMP-mediated degradation. Collectively, these microrheological measurements provide insight into microscopic, cellular manipulation of the pericellular region that gives rise to macroscopic tracks created in scaffolds by migrating cells. This quantitative and predictable information should benefit the design of improved biomaterial scaffolds for medically relevant applications.PEG-peptide hydrogels | human mesenchymal stem cells | cell migration | microrheology

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“…When the patterned attachable area becomes overloaded, the cells will expand to the hydrogel areas probably by expressing proteins and utilizing the growth force to damage the structure of the hydrogel. 36 As shown in Fig. 11, we find that for different PEGDA films that act as a block, and for different adhesive channels with different widths, the total elapsed time and ratio of cells displaying expansion behavior is different.…”

Section: Effects Of Geometry and Size Of Polymer Structures On Cellsmentioning

confidence: 77%

Extracellular-controlled breast cancer cell formation and growth using non-UV patterned hydrogels via optically-induced electrokinetics

et al. 2014

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The culturing of cancer cells on micropatterned substrates can provide insight into the factors of the extracellular environment that enable the control of cell growth. We report here a novel non-UV-based technique to quickly micropattern a poly-(ethylene) glycol diacrylate (PEGDA)-based hydrogel on top of modified glass substrates, which were then used to control the growth patterns of breast cancer cells. Previously, the fabrication of micropatterned substrates required relatively complicated steps, which made it impractical for researchers to rapidly and systematically investigate the effects of different cell growth patterns. The technique presented herein operates on the principle of optically-induced electrokinetics (OEKs) and uses computer-generated projection light patterns to dynamically pattern the hydrogel on a hydrogenated amorphous silicon (a-Si:H) thin-film, atop an indium tin oxide (ITO) glass substrate. This technique allows us to pattern lines, circles, pentagons, and more complex shapes in the hydrogel with line widths below 3 μm and thicknesses of up to 6 μm within 8 s by simply controlling the projected illumination pattern and applying an appropriate AC voltage between the two ITO glass substrates. After separating the glass substrates to expose the patterned hydrogel, we experimentally demonstrate that MCF-7 breast cancer cells will adhere to the bare a-Si:H surface, but not to the hydrogel patterned in various geometric shapes and sizes. Theoretical analysis and finite-element model simulations reveal that the dominant OEK forces in our technique are the dielectrophoresis (DEP) force and the electro-osmosis force, which enhance the photo-initiated cross-linking reaction in the hydrogel. Our preliminary cultures of breast cancer cells demonstrate that this reported technique could be applied to effectively confine the growth of cancer cells on a-Si:H surfaces and affect individual cell geometry during their growth.

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Mechanical Properties of Cellularly Responsive Hydrogels and Their Experimental Determination

Cited by 428 publications

References 116 publications

Poly(vinyl alcohol)-heparin biosynthetic microspheres produced by microfluidics and ultraviolet photopolymerisation

Poly(vinyl alcohol)-heparin biosynthetic microspheres produced by microfluidics and ultraviolet photopolymerisation

Measuring dynamic cell–material interactions and remodeling during 3D human mesenchymal stem cell migration in hydrogels

Extracellular-controlled breast cancer cell formation and growth using non-UV patterned hydrogels via optically-induced electrokinetics

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