Stem cells might be coaxed to develop into new bone or new cartilage better and faster when given the proper molecular cues and room inside a water-loving gel, researchers at Case Western Reserve University show.
By creating a three-dimensional checkerboard—one with alternating highly connected and less connected spaces from the hydrogel— the team found adjusting how big the micropattern could affect stem cell behaviors, for instance proliferation and differentiation.
Inducing where stem cells grow—and in the appropriate cell in three dimensions—has proven quite a job to making useful stem cell therapies. It holds promise for studying how physical, chemical and also other influences affect cell behavior in three-dimensions, and, ultimately, as being a strategy to grow tissues for regenerative medicine applications.
“The world thinks that control over local biomaterial properties may allow us move the formation of complex tissues,” said Eben Alsberg, an associate professor of Biomedical Engineering at Case Western Reserve. “Using this type of system, we are able to regulate cell proliferation and cell-specific differentiation into, e.g., bone-like or cartilage-like cells.”
Oju Jeon, PhD, a postdoctoral researcher in Biomedical Engineering, pursued this work with Alsberg. Their effort is described April 11, 2013 in the online edition of Advanced Functional Materials.
Hydrogels are hydrophilic three-dimensional networks of water-soluble polymers bonded, or crosslinked, to one another. Crosslinks increase rigidity and customize the porous structure from the gel.
Alsberg and Jeon used a hydrogel of oxidized methacrylated alginate and an 8-arm poly(ethanediol) amine. A chemical reaction between the alginate as well as the poly(ethanediol) creates crosslinks that provide structure from the gel.
They tweaked the mix to ensure an additional number of crosslinks forms when confronted with light. They used checkerboard masks to create patterns of alternating singly and doubly crosslinked spaces.
The spaces, which varied bigger at 25, 50, 100 and 200 micrometers across, were evenly singly and doubly crosslinked.
Human stem cells isolated from fat tissue were encapsulated inside the singly and doubly crosslinked regions. The doubly-crosslinked spaces are comparatively cluttered with structures. The cells grew into clusters inside singly-crosslinked regions, but remained mostly isolated within the doubly crosslinked regions.
The bigger the spaces in the checkerboard, the greater the clusters grew.
Cells were cultivated in media that promote differentiation into either bone or cartilage.
In both the singly and doubly crosslinked spaces, stem cells increasingly differentiated in line with the media composition because the space size increased. The outcome were more dramatic from the singly-crosslinked spaces.
“Potentially, what’s happening is the single-crosslinked regions allow better nutrient transport and supply more space for cells to interact and, because it’s less restrictive, there’s space for new cells and matrix production,” Alsberg said. “Cluster formation, therefore, may influence proliferation and differentiation. Differences in mechanical properties between regions likely also regulate the cell behaviors.”
The study are continuing to work with micropatterning to recognise the influences of biomaterials on stem cell fate decisions. This strategy may permit local control over cell behavior and, ultimately, encourage the engineering of complex tissues comprised of multiple cell types by using a single stem cell source.
Source: Case Western Reserve University
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