Biomineralized composite substrates increase gene expression with nonviral delivery

Rameshwar R. Rao, Jiawei He, Jonathan K Leach

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Current strategies to enhance gene transfer have focused on the development of vectors to increase the efficiency of DNA delivery. However, the extracellular matrix and microenvironment have a profound impact on numerous cellular activities including spreading and proliferation; two processes that have been associated with gene transfer efficiency. This study was designed to test the hypothesis that the presence of a biomineralized coating on biodegradable substrates would affect transgene expression following nonviral gene delivery. Thin films were prepared from polymeric microspheres, while biomineralized films were fabricated from microspheres previously soaked in modified simulated body fluid. Mineralized films were significantly more rigid and had widespread mineral coverage compared with nonmineralized substrates. Human mesenchymal stem cells (MSCs) were cultured on biomineralized or nonmineralized films and transfected with plasmid DNA condensed with linear polyethyleneimine (PEI). Compared with cells transfected on nonmineralized films, increases in gene expression were detected in the presence of biomineral at all charge ratios examined. We observed increased uptake of both PEI and DNA by cells on mineralized films. The results of these studies offer an approach to modulate gene delivery and improve the potential benefit of nonviral gene delivery approaches.

Original languageEnglish (US)
Pages (from-to)344-354
Number of pages11
JournalJournal of Biomedical Materials Research - Part A
Volume94
Issue number2
DOIs
StatePublished - Aug 2010

Fingerprint

Gene expression
Composite materials
Gene transfer
Substrates
Polyethyleneimine
DNA
Genes
Microspheres
Body fluids
Stem cells
Minerals
Plasmids
Thin films
Coatings

Keywords

  • Biomineralization
  • Gene expression
  • Mesenchymal stem cells
  • Nonviral gene therapy
  • SBF

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials
  • Ceramics and Composites
  • Metals and Alloys

Cite this

Biomineralized composite substrates increase gene expression with nonviral delivery. / Rao, Rameshwar R.; He, Jiawei; Leach, Jonathan K.

In: Journal of Biomedical Materials Research - Part A, Vol. 94, No. 2, 08.2010, p. 344-354.

Research output: Contribution to journalArticle

Rao, Rameshwar R. ; He, Jiawei ; Leach, Jonathan K. / Biomineralized composite substrates increase gene expression with nonviral delivery. In: Journal of Biomedical Materials Research - Part A. 2010 ; Vol. 94, No. 2. pp. 344-354.
@article{10988120f1a44df0b8c8d1993ffcc1bc,
title = "Biomineralized composite substrates increase gene expression with nonviral delivery",
abstract = "Current strategies to enhance gene transfer have focused on the development of vectors to increase the efficiency of DNA delivery. However, the extracellular matrix and microenvironment have a profound impact on numerous cellular activities including spreading and proliferation; two processes that have been associated with gene transfer efficiency. This study was designed to test the hypothesis that the presence of a biomineralized coating on biodegradable substrates would affect transgene expression following nonviral gene delivery. Thin films were prepared from polymeric microspheres, while biomineralized films were fabricated from microspheres previously soaked in modified simulated body fluid. Mineralized films were significantly more rigid and had widespread mineral coverage compared with nonmineralized substrates. Human mesenchymal stem cells (MSCs) were cultured on biomineralized or nonmineralized films and transfected with plasmid DNA condensed with linear polyethyleneimine (PEI). Compared with cells transfected on nonmineralized films, increases in gene expression were detected in the presence of biomineral at all charge ratios examined. We observed increased uptake of both PEI and DNA by cells on mineralized films. The results of these studies offer an approach to modulate gene delivery and improve the potential benefit of nonviral gene delivery approaches.",
keywords = "Biomineralization, Gene expression, Mesenchymal stem cells, Nonviral gene therapy, SBF",
author = "Rao, {Rameshwar R.} and Jiawei He and Leach, {Jonathan K}",
year = "2010",
month = "8",
doi = "10.1002/jbm.a.32690",
language = "English (US)",
volume = "94",
pages = "344--354",
journal = "Journal of Biomedical Materials Research - Part A",
issn = "1549-3296",
publisher = "Heterocorporation",
number = "2",

}

TY - JOUR

T1 - Biomineralized composite substrates increase gene expression with nonviral delivery

AU - Rao, Rameshwar R.

AU - He, Jiawei

AU - Leach, Jonathan K

PY - 2010/8

Y1 - 2010/8

N2 - Current strategies to enhance gene transfer have focused on the development of vectors to increase the efficiency of DNA delivery. However, the extracellular matrix and microenvironment have a profound impact on numerous cellular activities including spreading and proliferation; two processes that have been associated with gene transfer efficiency. This study was designed to test the hypothesis that the presence of a biomineralized coating on biodegradable substrates would affect transgene expression following nonviral gene delivery. Thin films were prepared from polymeric microspheres, while biomineralized films were fabricated from microspheres previously soaked in modified simulated body fluid. Mineralized films were significantly more rigid and had widespread mineral coverage compared with nonmineralized substrates. Human mesenchymal stem cells (MSCs) were cultured on biomineralized or nonmineralized films and transfected with plasmid DNA condensed with linear polyethyleneimine (PEI). Compared with cells transfected on nonmineralized films, increases in gene expression were detected in the presence of biomineral at all charge ratios examined. We observed increased uptake of both PEI and DNA by cells on mineralized films. The results of these studies offer an approach to modulate gene delivery and improve the potential benefit of nonviral gene delivery approaches.

AB - Current strategies to enhance gene transfer have focused on the development of vectors to increase the efficiency of DNA delivery. However, the extracellular matrix and microenvironment have a profound impact on numerous cellular activities including spreading and proliferation; two processes that have been associated with gene transfer efficiency. This study was designed to test the hypothesis that the presence of a biomineralized coating on biodegradable substrates would affect transgene expression following nonviral gene delivery. Thin films were prepared from polymeric microspheres, while biomineralized films were fabricated from microspheres previously soaked in modified simulated body fluid. Mineralized films were significantly more rigid and had widespread mineral coverage compared with nonmineralized substrates. Human mesenchymal stem cells (MSCs) were cultured on biomineralized or nonmineralized films and transfected with plasmid DNA condensed with linear polyethyleneimine (PEI). Compared with cells transfected on nonmineralized films, increases in gene expression were detected in the presence of biomineral at all charge ratios examined. We observed increased uptake of both PEI and DNA by cells on mineralized films. The results of these studies offer an approach to modulate gene delivery and improve the potential benefit of nonviral gene delivery approaches.

KW - Biomineralization

KW - Gene expression

KW - Mesenchymal stem cells

KW - Nonviral gene therapy

KW - SBF

UR - http://www.scopus.com/inward/record.url?scp=77953861193&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953861193&partnerID=8YFLogxK

U2 - 10.1002/jbm.a.32690

DO - 10.1002/jbm.a.32690

M3 - Article

C2 - 20186740

AN - SCOPUS:77953861193

VL - 94

SP - 344

EP - 354

JO - Journal of Biomedical Materials Research - Part A

JF - Journal of Biomedical Materials Research - Part A

SN - 1549-3296

IS - 2

ER -