Get access

Peptide-modified alginate surfaces as a growth permissive substrate for neurite outgrowth

Authors

  • Nikhil O. Dhoot,

    1. School of Biomedical Engineering, Science and Health Systems, Drexel University, 32nd and Chestnut Streets, Philadelphia, Pennsylvania 19104-2875
    2. Department of Chemical Engineering, Drexel University, 32nd and Chestnut Streets, Philadelphia, Pennsylvania 19104-2875
    Search for more papers by this author
  • Chris A. Tobias,

    1. Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, Pennsylvania 19129
    Search for more papers by this author
  • Itzhak Fischer,

    1. Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, Pennsylvania 19129
    Search for more papers by this author
  • Margaret A. Wheatley

    Corresponding author
    1. School of Biomedical Engineering, Science and Health Systems, Drexel University, 32nd and Chestnut Streets, Philadelphia, Pennsylvania 19104-2875
    • School of Biomedical Engineering, Science and Health Systems, Drexel University, 32nd and Chestnut Streets, Philadelphia, Pennsylvania 19104-2875
    Search for more papers by this author

Abstract

Different strategies are being investigated for treatment of spinal cord injuries, one of the most promising being application of neurotrophic factors, which have been shown to prevent neuronal death and stimulate regeneration of injured axons. Ex vivo gene therapy has emerged as the leading delivery method at the site of the injury, and we have shown previously that encapsulating genetically engineered fibroblasts in an immunoprotective alginate capsule can permit implantation of the factor-secreting cells without need for immunosuppression. This strategy could be greatly enhanced by providing the sprouting neurons with a permissive substrate upon which to attach and grow. We report here studies on the modification of an alginate gel surface by either coating it with laminin or by covalent attachment of YIGSR peptide. Using NB2a neuroblastoma cells, we found that native alginate elicited minimal cell attachment (∼1.5%); however, YIGSR-alginate conjugate elicited a fivefold increase in numbers of cells attached using peptide ratios of 0.5 and 1 mg/g alginate, ranging from 9.5% of the cells at the lower ratio, to about 44% at the higher. Only a further 19% increase was obtained at an increased peptide density of 2 mg/g alginate (∼63% over control). Laminin-coated gels showed ∼60% cell attachment. However, laminin coating did not stimulate differentiation and neurite growth, whereas both numbers and lengths of outgrowths increased with increasing peptide density on peptide-modified alginate. We demonstrate here the ability of the peptide-modified alginate gels to allow adhesion of NB2a neuroblastoma cells and to promote neurite outgrowth from these cells when attached to the peptide-modified alginate surface. Also, we show that the adhesion of NB2a neuroblastoma cells and neurite outgrowth from the attached cells is a function of the peptide density on the gel surface. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 191–200, 2004

Get access to the full text of this article

Ancillary