The effect of injectable gelatin-hydroxyphenylpropionic acid hydrogel matrices on the proliferation, migration, differentiation and oxidative stress resistance of adult neural stem cells

Biomaterials. 2012 Apr;33(12):3446-55. doi: 10.1016/j.biomaterials.2012.01.037. Epub 2012 Feb 4.


Transplanted or endogenous neural stem cells often lack appropriate matrix in cavitary lesions in the central nervous system. In this study, gelatin-hydroxyphenylpropionic acid (Gtn-HPA), which could be enzymatically crosslinked with independent tuning of crosslinking degree and gelation rate, was explored as an injectable hydrogel for adult neural stem cells (aNSCs). The storage modulus of Gtn-HPA could be tuned (449-1717 Pa) to approximate adult brain tissue. Gtn-HPA was cytocompatible with aNSCs (yielding high viability >93%) and promoted aNSC adhesion. Gtn-HPA demonstrated a crosslinking-based approach for preconditioning aNSCs and increased the resistance of aNSCs to oxidative stress, improving their viability from 8-15% to 84% when challenged with 500 μM H(2)O(2). In addition, Gtn-HPA was able to modulate proliferation and migration of aNSCs in relation to the crosslinking degree. Finally, Gtn-HPA exhibited bias for neuronal cells. In mixed differentiation conditions, Gtn-HPA increased the proportion of aNSCs expressing neuronal marker β-tubulin III to a greater extent than that for astrocytic marker glial fibrillary acidic protein, indicating an enhancement in differentiation towards neuronal lineage. Between neuronal and astrocytic differentiation conditions, Gtn-HPA also selected for higher survival in the former. Overall, Gtn-HPA hydrogels are promising injectable matrices for supporting and influencing aNSCs in ways that may be beneficial for brain tissue regeneration after injuries.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult Stem Cells / cytology*
  • Adult Stem Cells / metabolism
  • Animals
  • Biocompatible Materials / administration & dosage
  • Biocompatible Materials / metabolism*
  • Cell Differentiation
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Gelatin / administration & dosage
  • Gelatin / metabolism*
  • Hydrogel, Polyethylene Glycol Dimethacrylate / administration & dosage
  • Hydrogel, Polyethylene Glycol Dimethacrylate / metabolism
  • Injections
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism
  • Oxidative Stress
  • Phenylpropionates / administration & dosage
  • Phenylpropionates / metabolism*
  • Rats


  • Biocompatible Materials
  • Phenylpropionates
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Gelatin