Chemotactic recruitment of adult neural progenitor cells into multifunctional hydrogels providing sustained SDF-1α release and compatible structural support

FASEB J. 2013 Mar;27(3):1023-33. doi: 10.1096/fj.12-221515. Epub 2012 Nov 27.


Without chemotactic cues and structural support, cavitary brain lesions typically fail to recruit endogenous neural progenitor cells (NPCs). Toward resolving this, we engineered multifunctional biomaterials comprising injectable gelatin-hydroxyphenylpropionic acid (Gtn-HPA) hydrogels and dextran sulfate/chitosan polyelectrolyte complex nanoparticles (PCNs) that delivered stromal cell-derived factor-1α (SDF-1α). Over 7 d of interface with in vitro tissue simulant containing adult rat hippocampal NPCs (aNPCs) and their neuronal progeny, Gtn-HPA/SDF-1α-PCN hydrogels promoted chemotactic recruitment to enhance infiltration of aNPCs by 3- to 45-fold relative to hydrogels that lacked SDF-1α or vehicles to sustain SDF-1α release. When cross-linked with 0.85-0.95 mM HO, Gtn-HPA/SDF-1α-PCN hydrogels provided optimally permissive structural support for migration of aNPCs. Specific matrix metalloproteinase (MMP) inhibitors revealed that 42, 30, and 55% of cell migration into Gtn-HPA/SDF-1α-PCN hydrogels involved MMP-2, 3, and 9, respectively, demonstrating the hydrogels to be compatible toward homing endogenous NPCs, given their expression of similar MMPs. Interestingly, PCNs utilized FGF-2 found in situ to induce chemokinesis, potentiate SDF-1α chemotactic recruitment, and increase proliferation of recruited cells, which collectively orchestrated a higher number of migrated aNPCs. Overall, Gtn-HPA/SDF-1α-PCN hydrogels prove to be promising biomaterials for injection into cavitary brain lesions to recruit endogenous NPCs and enhance neural tissue repair/regeneration.

Publication types

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

MeSH terms

  • Adult Stem Cells / metabolism*
  • Adult Stem Cells / pathology
  • Animals
  • Brain Injuries / pathology
  • Brain Injuries / therapy
  • Chemokine CXCL12 / pharmacology*
  • Chemotaxis / drug effects*
  • Collagenases / pharmacology
  • Delayed-Action Preparations / pharmacology
  • Female
  • Fibroblast Growth Factor 2 / metabolism
  • Hydrogels / pharmacology*
  • Matrix Metalloproteinase Inhibitors / pharmacology
  • Nanoparticles*
  • Neural Stem Cells / metabolism*
  • Neural Stem Cells / pathology
  • Rats
  • Rats, Inbred F344


  • CXCL12 protein, rat
  • Chemokine CXCL12
  • Delayed-Action Preparations
  • Hydrogels
  • Matrix Metalloproteinase Inhibitors
  • Fibroblast Growth Factor 2
  • Collagenases