title: Coiled polymeric growth factor gradients for multi-luminal neural chemotaxis.
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: Department of Bioengineering, University of Texas at Dallas, 800 W. Campbell Rd., EC39, Richardson, 75080 TX, USA.
authors: Nesreen Zoghoul
authors: NZ
authors: Alsmadi
authors: Department of Bioengineering, University of Texas Arlington, Arlington, TX, USA.
authors: Lokesh S
authors: LS
authors: Patil
authors: Department of Bioengineering, University of Texas Arlington, Arlington, TX, USA.
authors: Elijah M
authors: EM
authors: Hor
authors: Department of Bioengineering, University of Texas Arlington, Arlington, TX, USA.
authors: Parisa
authors: P
authors: Lofti
authors: ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Wollongong, NSW 2522, Australia.
authors: Joselito M
authors: JM
authors: Razal
authors: Department of Bioengineering, University of Texas Arlington, Arlington, TX, USA.
authors: Cheng-Jen
authors: CJ
authors: Chuong
authors: ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Wollongong, NSW 2522, Australia.
authors: Gordon G
authors: GG
authors: Wallace
authors: Department of Bioengineering, University of Texas at Dallas, 800 W. Campbell Rd., EC39, Richardson, 75080 TX, USA. Electronic address: Mario.romero-ortega@utdalllas.edu.
authors: Mario I
authors: MI
authors: Romero-Ortega
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D002633:Chemotaxis / Q000187:drug effects*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects*; D016716:PC12 Cells; D011108:Polymers / Q000494:pharmacology; D051381:Rats
chemical_list: D011108:Polymers; D020932:Nerve Growth Factor
keywords: Axon guidance; Dorsal root ganglia; Nerve growth factor; Nerve scaffolds; Sensory neurons