Coiled polymeric growth factor gradients for multi-luminal neural chemotaxis

Alsmadi, Nesreen Zoghoul, Patil, Lokesh S., Hor, Elijah M., Lofti, Parisa, Razal, Joselito M., Chuong, Cheng-Jen, Wallace, Gordon G. and Romero-Ortega, Mario I. 2015, Coiled polymeric growth factor gradients for multi-luminal neural chemotaxis, Brain research, vol. 1619, pp. 72-83, doi: 10.1016/j.brainres.2015.01.055.

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Title Coiled polymeric growth factor gradients for multi-luminal neural chemotaxis
Author(s) Alsmadi, Nesreen Zoghoul
Patil, Lokesh S.
Hor, Elijah M.
Lofti, Parisa
Razal, Joselito M.ORCID iD for Razal, Joselito M.
Chuong, Cheng-Jen
Wallace, Gordon G.
Romero-Ortega, Mario I.
Journal name Brain research
Volume number 1619
Start page 72
End page 83
Total pages 12
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2015-09
ISSN 1872-6240
Keyword(s) Axon guidance
Dorsal root ganglia
Nerve growth factor
Nerve scaffolds
Sensory neurons
Summary 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 collagen-filled 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 three-dimensional 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.
Language eng
DOI 10.1016/j.brainres.2015.01.055
Field of Research 060103 Cell Development, Proliferation and Death
Socio Economic Objective 920111 Nervous System and Disorders
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Elsevier
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