The effects of hyaluronic acid hydrogels with tunable mechanical properties on neural progenitor cell differentiation.
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.
Seidlits
Stephanie K
SK
Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
Khaing
Zin Z
ZZ
Petersen
Rebecca R
RR
Nickels
Jonathan D
JD
Vanscoy
Jennifer E
JE
Shear
Jason B
JB
Schmidt
Christine E
CE
D000812:Anhydrides / Q000737:chemistry; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology*; D008422:Materials Testing; D055595:Mechanical Phenomena / Q000187:drug effects*; D008689:Methacrylates / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D013116:Spinal Cord / Q000166:cytology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism
D000812:Anhydrides; D020100:Hydrogels; D008689:Methacrylates; D006820:Hyaluronic Acid