The effects of hyaluronic acid hydrogels with tunable mechanical properties on neural progenitor cell differentiation

Abstract We report the ability to direct the differentiation pathway of neural progenitor cells (NPCs) within hydrogels having tunable mechanical properties. By modifying the polymeric sugar hyaluronic acid (HA), a major extracellular matrix component in the fetal mammalian brain, with varying numbe...

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Bibliographic Details
Published in:Biomaterials 2010-05, Vol.31 (14), p.3930-3940
Main Authors: Seidlits, Stephanie K, Khaing, Zin Z, Petersen, Rebecca R, Nickels, Jonathan D, Vanscoy, Jennifer E, Shear, Jason B, Schmidt, Christine E
Format: Article
Language:English
Subjects:
Advanced Basic Science
Anhydrides - chemistry
Animals
Astrocyte
Astrocytes - cytology
Astrocytes - drug effects
Astrocytes - metabolism
Cell Differentiation - drug effects
Cells, Cultured
Dentistry
Hyaluronic Acid - chemistry
Hyaluronic Acid - pharmacology
Hyaluronic acid/hyaluronan
Hydrogel
Hydrogels - chemistry
Hydrogels - pharmacology
Materials Testing
Mechanical Phenomena - drug effects
Methacrylates - chemistry
Mice
Mice, Inbred C57BL
Neural cell
Neurons - cytology
Neurons - drug effects
Neurons - metabolism
Phenotype
Progenitor cell
Rats
Spinal Cord - cytology
Stem Cells - cytology
Stem Cells - drug effects
Stem Cells - metabolism
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Summary:Abstract We report the ability to direct the differentiation pathway of neural progenitor cells (NPCs) within hydrogels having tunable mechanical properties. By modifying the polymeric sugar hyaluronic acid (HA), a major extracellular matrix component in the fetal mammalian brain, with varying numbers of photocrosslinkable methacrylate groups, hydrogels could be prepared with bulk compressive moduli spanning the threefold range measured for neonatal brain and adult spinal cord. Ventral midbrain-derived NPCs were photoencapsulated into HA hydrogels and remained viable after encapsulation. After three weeks, the majority of NPCs cultured in hydrogels with mechanical properties comparable to those of neonatal brain had differentiated into neurons (ß-III tubulin-positive), many of which had extended long, branched processes, indicative of a relatively mature phenotype. In contrast, NPCs within stiffer hydrogels, with mechanical properties comparable to those of adult brain, had differentiated into mostly astrocytes (glial fibrillary acidic protein (GFAP)-positive). Primary spinal astrocytes cultured in the hydrogel variants for two weeks acquired a spread and elongated morphology only in the stiffest hydrogels evaluated, with mechanical properties similar to adult tissue. Results demonstrate that the mechanical properties of these scaffolds can assert a defining influence on the differentiation of ventral midbrain-derived NPCs, which have strong clinical relevance because of their ability to mature into dopaminergic neurons of the substantia nigra, cells that idiopathically degenerate in individuals suffering from Parkinson's disease.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2010.01.125