Patterned PLG substrates for localized DNA delivery and directed neurite extension

Tiffany Houchin-Ray, Laura A. Swift, Jae-Hyung Jang, Lonnie D. Shea

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Tissue engineering strategies that enable nerve regeneration will require methods that can promote and direct neurite extension across the lesion. In this report, we investigate an in vitro combinatorial approach to directed neurite outgrowth using gene delivery from topographically patterned substrates, which can induce expression of neurotrophic factors to promote neurite extension and direct the extending neurites. Poly(lactide-co-glycolide) (PLG), which has been used to fabricate conduits or bridges for regeneration, was compression molded to create channels with 100, 150, and 250 μm widths. DNA complexes were immobilized to the PLG, and cells cultured on the substrate were transfected with efficiencies dependent on channel width and DNA amount. A co-culture model consisting of primary neurons and accessory cells was employed to investigate neurite outgrowth within the channels. Localized secretion of nerve growth factor (NGF) by the accessory cells promoted neuron survival and neurite extension. Neurons cultured in channels with NGF expression exhibited longer primary neurites than in the absence of channels. Neurons cultured in smaller width PLG microchannels exhibited a greater degree of directionality and less secondary sprouting than larger channels. Finally, surface immobilization allowed for the delivery of distinct plasmids from each channel, which may enable channels to be tailored for specific nerve tracts. This approach demonstrates the ability to combine gene delivery with physical guidance, and can be tailored to target specific axonal populations with varying neurotrophic factor requirements.

Original languageEnglish
Pages (from-to)2603-2611
Number of pages9
JournalBiomaterials
Volume28
Issue number16
DOIs
Publication statusPublished - 2007 Jun 1

Fingerprint

Neurites
Neurons
DNA
Nerve Growth Factors
Accessories
Nerve Growth Factor
Substrates
Genes
Polyglactin 910
Microchannels
Tissue engineering
Nerve Regeneration
Tissue Engineering
Coculture Techniques
Plasmids
Immobilization
Regeneration
Cultured Cells
Population
Intercellular Signaling Peptides and Proteins

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

Cite this

Houchin-Ray, Tiffany ; Swift, Laura A. ; Jang, Jae-Hyung ; Shea, Lonnie D. / Patterned PLG substrates for localized DNA delivery and directed neurite extension. In: Biomaterials. 2007 ; Vol. 28, No. 16. pp. 2603-2611.
@article{a880be38f502473cb613ea5af2e89a1c,
title = "Patterned PLG substrates for localized DNA delivery and directed neurite extension",
abstract = "Tissue engineering strategies that enable nerve regeneration will require methods that can promote and direct neurite extension across the lesion. In this report, we investigate an in vitro combinatorial approach to directed neurite outgrowth using gene delivery from topographically patterned substrates, which can induce expression of neurotrophic factors to promote neurite extension and direct the extending neurites. Poly(lactide-co-glycolide) (PLG), which has been used to fabricate conduits or bridges for regeneration, was compression molded to create channels with 100, 150, and 250 μm widths. DNA complexes were immobilized to the PLG, and cells cultured on the substrate were transfected with efficiencies dependent on channel width and DNA amount. A co-culture model consisting of primary neurons and accessory cells was employed to investigate neurite outgrowth within the channels. Localized secretion of nerve growth factor (NGF) by the accessory cells promoted neuron survival and neurite extension. Neurons cultured in channels with NGF expression exhibited longer primary neurites than in the absence of channels. Neurons cultured in smaller width PLG microchannels exhibited a greater degree of directionality and less secondary sprouting than larger channels. Finally, surface immobilization allowed for the delivery of distinct plasmids from each channel, which may enable channels to be tailored for specific nerve tracts. This approach demonstrates the ability to combine gene delivery with physical guidance, and can be tailored to target specific axonal populations with varying neurotrophic factor requirements.",
author = "Tiffany Houchin-Ray and Swift, {Laura A.} and Jae-Hyung Jang and Shea, {Lonnie D.}",
year = "2007",
month = "6",
day = "1",
doi = "10.1016/j.biomaterials.2007.01.042",
language = "English",
volume = "28",
pages = "2603--2611",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",
number = "16",

}

Patterned PLG substrates for localized DNA delivery and directed neurite extension. / Houchin-Ray, Tiffany; Swift, Laura A.; Jang, Jae-Hyung; Shea, Lonnie D.

In: Biomaterials, Vol. 28, No. 16, 01.06.2007, p. 2603-2611.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Patterned PLG substrates for localized DNA delivery and directed neurite extension

AU - Houchin-Ray, Tiffany

AU - Swift, Laura A.

AU - Jang, Jae-Hyung

AU - Shea, Lonnie D.

PY - 2007/6/1

Y1 - 2007/6/1

N2 - Tissue engineering strategies that enable nerve regeneration will require methods that can promote and direct neurite extension across the lesion. In this report, we investigate an in vitro combinatorial approach to directed neurite outgrowth using gene delivery from topographically patterned substrates, which can induce expression of neurotrophic factors to promote neurite extension and direct the extending neurites. Poly(lactide-co-glycolide) (PLG), which has been used to fabricate conduits or bridges for regeneration, was compression molded to create channels with 100, 150, and 250 μm widths. DNA complexes were immobilized to the PLG, and cells cultured on the substrate were transfected with efficiencies dependent on channel width and DNA amount. A co-culture model consisting of primary neurons and accessory cells was employed to investigate neurite outgrowth within the channels. Localized secretion of nerve growth factor (NGF) by the accessory cells promoted neuron survival and neurite extension. Neurons cultured in channels with NGF expression exhibited longer primary neurites than in the absence of channels. Neurons cultured in smaller width PLG microchannels exhibited a greater degree of directionality and less secondary sprouting than larger channels. Finally, surface immobilization allowed for the delivery of distinct plasmids from each channel, which may enable channels to be tailored for specific nerve tracts. This approach demonstrates the ability to combine gene delivery with physical guidance, and can be tailored to target specific axonal populations with varying neurotrophic factor requirements.

AB - Tissue engineering strategies that enable nerve regeneration will require methods that can promote and direct neurite extension across the lesion. In this report, we investigate an in vitro combinatorial approach to directed neurite outgrowth using gene delivery from topographically patterned substrates, which can induce expression of neurotrophic factors to promote neurite extension and direct the extending neurites. Poly(lactide-co-glycolide) (PLG), which has been used to fabricate conduits or bridges for regeneration, was compression molded to create channels with 100, 150, and 250 μm widths. DNA complexes were immobilized to the PLG, and cells cultured on the substrate were transfected with efficiencies dependent on channel width and DNA amount. A co-culture model consisting of primary neurons and accessory cells was employed to investigate neurite outgrowth within the channels. Localized secretion of nerve growth factor (NGF) by the accessory cells promoted neuron survival and neurite extension. Neurons cultured in channels with NGF expression exhibited longer primary neurites than in the absence of channels. Neurons cultured in smaller width PLG microchannels exhibited a greater degree of directionality and less secondary sprouting than larger channels. Finally, surface immobilization allowed for the delivery of distinct plasmids from each channel, which may enable channels to be tailored for specific nerve tracts. This approach demonstrates the ability to combine gene delivery with physical guidance, and can be tailored to target specific axonal populations with varying neurotrophic factor requirements.

UR - http://www.scopus.com/inward/record.url?scp=33847681043&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847681043&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2007.01.042

DO - 10.1016/j.biomaterials.2007.01.042

M3 - Article

VL - 28

SP - 2603

EP - 2611

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

IS - 16

ER -