Coiled polymeric growth factor gradients for multi-luminal neural chemotaxis

Journal Article


Abstract


  • In the injured adult nervous system, re-establishment of growth-promoting molecular gradients is known to entice and guide nerve repair. However, incorporation of three-dimensional chemotactic gradients in nerve repair scaffolds, particularly in those with multi-luminal architectures, remains extremely challenging. We developed a method that establishes highly tunable three-dimensional molecular gradients in multi-luminal nerve guides by anchoring growth-factor releasing coiled polymeric fibers onto the walls of collagen-filled hydrogel microchannels. Differential pitch in the coiling of neurotrophin-eluting fibers generated sustained chemotactic gradients that appropriately induced the differentiation of Pheochromocytoma (PC12) cells into neural-like cells along an increasing concentration of nerve growth factor (NGF). Computer modeling estimated the stability of the molecular gradient within the luminal collagen, which we confirmed by observing the significant effects of neurotrophin gradients on axonal growth from dorsal root ganglia (DRG). Neurons growing in microchannels exposed to a NGF gradient showed a 60% increase in axonal length compared to those treated with a linear growth factor concentration. In addition, a two-fold increment in the linearity of axonal growth within the microchannels was observed and confirmed by a significant reduction in the turning angle ratios of individual axons. These data demonstrate the ability of growth factor-loaded polymeric coiled fibers to establish three-dimensional chemotactic gradients to promote and direct nerve regeneration in the nervous system and provides a unique platform for molecularly guided tissue repair.

Authors


  •   Alsmadi, Nesreen Zoghoul (external author)
  •   Patil, Lokesh S. (external author)
  •   Hor, Elijah M. M. (external author)
  •   Lofti, Parisa (external author)
  •   Razal, Joselito M. (external author)
  •   Chuong, Cheng-Jen (external author)
  •   Wallace, Gordon G.
  •   Romero-Ortega, Mario I. (external author)

Publication Date


  • 2015

Citation


  • Alsmadi, N., Patil, L. S., Hor, E. M., Lofti, P., Razal, J. M., Chuong, C., Wallace, G. G. & Romero-Ortega, M. I. (2015). Coiled polymeric growth factor gradients for multi-luminal neural chemotaxis. Brain Research, 1619 72-83.

Scopus Eid


  • 2-s2.0-84928183039

Ro Metadata Url


  • http://ro.uow.edu.au/aiimpapers/1470

Has Global Citation Frequency


Number Of Pages


  • 11

Start Page


  • 72

End Page


  • 83

Volume


  • 1619

Place Of Publication


  • Netherlands

Abstract


  • In the injured adult nervous system, re-establishment of growth-promoting molecular gradients is known to entice and guide nerve repair. However, incorporation of three-dimensional chemotactic gradients in nerve repair scaffolds, particularly in those with multi-luminal architectures, remains extremely challenging. We developed a method that establishes highly tunable three-dimensional molecular gradients in multi-luminal nerve guides by anchoring growth-factor releasing coiled polymeric fibers onto the walls of collagen-filled hydrogel microchannels. Differential pitch in the coiling of neurotrophin-eluting fibers generated sustained chemotactic gradients that appropriately induced the differentiation of Pheochromocytoma (PC12) cells into neural-like cells along an increasing concentration of nerve growth factor (NGF). Computer modeling estimated the stability of the molecular gradient within the luminal collagen, which we confirmed by observing the significant effects of neurotrophin gradients on axonal growth from dorsal root ganglia (DRG). Neurons growing in microchannels exposed to a NGF gradient showed a 60% increase in axonal length compared to those treated with a linear growth factor concentration. In addition, a two-fold increment in the linearity of axonal growth within the microchannels was observed and confirmed by a significant reduction in the turning angle ratios of individual axons. These data demonstrate the ability of growth factor-loaded polymeric coiled fibers to establish three-dimensional chemotactic gradients to promote and direct nerve regeneration in the nervous system and provides a unique platform for molecularly guided tissue repair.

Authors


  •   Alsmadi, Nesreen Zoghoul (external author)
  •   Patil, Lokesh S. (external author)
  •   Hor, Elijah M. M. (external author)
  •   Lofti, Parisa (external author)
  •   Razal, Joselito M. (external author)
  •   Chuong, Cheng-Jen (external author)
  •   Wallace, Gordon G.
  •   Romero-Ortega, Mario I. (external author)

Publication Date


  • 2015

Citation


  • Alsmadi, N., Patil, L. S., Hor, E. M., Lofti, P., Razal, J. M., Chuong, C., Wallace, G. G. & Romero-Ortega, M. I. (2015). Coiled polymeric growth factor gradients for multi-luminal neural chemotaxis. Brain Research, 1619 72-83.

Scopus Eid


  • 2-s2.0-84928183039

Ro Metadata Url


  • http://ro.uow.edu.au/aiimpapers/1470

Has Global Citation Frequency


Number Of Pages


  • 11

Start Page


  • 72

End Page


  • 83

Volume


  • 1619

Place Of Publication


  • Netherlands