Photoactivated miR-148b-nanoparticle conjugates improve closure of critical size mouse calvarial defects

Ammar T. Qureshi, Andrew Doyle, Cong Chen, Diana Coulon, Vinod Dasa, Fabio DelPiero, Benjamin Levi, W. Todd Monroe, Jeffrey M. Gimble, Daniel J. Hayes

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Inducible systems providing temporal control of differentiation have the potential to improve outcomes in surgical reconstruction and regenerative medicine by precise modulation of wound healing and tissue repair processes. The aim of this study was to demonstrate that nanoformulated microRNA (miRNA) conjugates activated via photo exposure can lead to the induced osteogenic differentiation of human adipose-derived stromal/stem cells (hASCs) in vivo. The conjugate PC-miR-148b-SNP, a mimic of miRNA-148b tethered to silver nanoparticles (SNPs) via a photolabile linker, was used to modulate gene expression for improved closure of a critical size defect drilled on the right parietal bone of male CD-1 nude homozygous mice. The PC-miR-148b-SNP conjugates added to hASCs and loaded to either Matrigel or polycaprolactone (PCL) scaffolds resulted in different levels of healing of the defect. After 4 and 12 weeks, 3-D micro-computed tomography reconstructed images indicate statistically significant defect closure from 3.83 ± 1.19% to 5.46 ± 2.01% and 6.54 ± 4.28% to 32.53 ± 8.3% for non-photoactivated and photoactivated conjugates, respectively, in the PCL scaffolds. The results were confirmed with H&E and Masson's Trichrome stains in the transverse sections of photoactivated conjugates. Collagen fiber staining was greatest at 12 weeks when it reached approximately the same density and thickness as the native calvarium. This technology provides a platform that can be used with other miRNAs that actively govern the pathways responsible for regenerative and wound healing processes.

Original languageEnglish (US)
Pages (from-to)166-173
Number of pages8
JournalActa Biomaterialia
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

MicroRNAs
Silver
Nanoparticles
Polycaprolactone
Stromal Cells
Stem cells
Scaffolds
Wound Healing
Defects
Stem Cells
Parietal Bone
Regenerative Medicine
Collagen
Skull
Gene expression
Nude Mice
Tomography
Bone
Repair
Modulation

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

Cite this

Qureshi, Ammar T. ; Doyle, Andrew ; Chen, Cong ; Coulon, Diana ; Dasa, Vinod ; DelPiero, Fabio ; Levi, Benjamin ; Monroe, W. Todd ; Gimble, Jeffrey M. ; Hayes, Daniel J. / Photoactivated miR-148b-nanoparticle conjugates improve closure of critical size mouse calvarial defects. In: Acta Biomaterialia. 2015 ; Vol. 12, No. 1. pp. 166-173.
@article{23fae2532b004cb5a83ec3a4fa5a476a,
title = "Photoactivated miR-148b-nanoparticle conjugates improve closure of critical size mouse calvarial defects",
abstract = "Inducible systems providing temporal control of differentiation have the potential to improve outcomes in surgical reconstruction and regenerative medicine by precise modulation of wound healing and tissue repair processes. The aim of this study was to demonstrate that nanoformulated microRNA (miRNA) conjugates activated via photo exposure can lead to the induced osteogenic differentiation of human adipose-derived stromal/stem cells (hASCs) in vivo. The conjugate PC-miR-148b-SNP, a mimic of miRNA-148b tethered to silver nanoparticles (SNPs) via a photolabile linker, was used to modulate gene expression for improved closure of a critical size defect drilled on the right parietal bone of male CD-1 nude homozygous mice. The PC-miR-148b-SNP conjugates added to hASCs and loaded to either Matrigel or polycaprolactone (PCL) scaffolds resulted in different levels of healing of the defect. After 4 and 12 weeks, 3-D micro-computed tomography reconstructed images indicate statistically significant defect closure from 3.83 ± 1.19{\%} to 5.46 ± 2.01{\%} and 6.54 ± 4.28{\%} to 32.53 ± 8.3{\%} for non-photoactivated and photoactivated conjugates, respectively, in the PCL scaffolds. The results were confirmed with H&E and Masson's Trichrome stains in the transverse sections of photoactivated conjugates. Collagen fiber staining was greatest at 12 weeks when it reached approximately the same density and thickness as the native calvarium. This technology provides a platform that can be used with other miRNAs that actively govern the pathways responsible for regenerative and wound healing processes.",
author = "Qureshi, {Ammar T.} and Andrew Doyle and Cong Chen and Diana Coulon and Vinod Dasa and Fabio DelPiero and Benjamin Levi and Monroe, {W. Todd} and Gimble, {Jeffrey M.} and Hayes, {Daniel J.}",
year = "2015",
month = "1",
day = "1",
doi = "10.1016/j.actbio.2014.10.010",
language = "English (US)",
volume = "12",
pages = "166--173",
journal = "Acta Biomaterialia",
issn = "1742-7061",
publisher = "Elsevier BV",
number = "1",

}

Qureshi, AT, Doyle, A, Chen, C, Coulon, D, Dasa, V, DelPiero, F, Levi, B, Monroe, WT, Gimble, JM & Hayes, DJ 2015, 'Photoactivated miR-148b-nanoparticle conjugates improve closure of critical size mouse calvarial defects', Acta Biomaterialia, vol. 12, no. 1, pp. 166-173. https://doi.org/10.1016/j.actbio.2014.10.010

Photoactivated miR-148b-nanoparticle conjugates improve closure of critical size mouse calvarial defects. / Qureshi, Ammar T.; Doyle, Andrew; Chen, Cong; Coulon, Diana; Dasa, Vinod; DelPiero, Fabio; Levi, Benjamin; Monroe, W. Todd; Gimble, Jeffrey M.; Hayes, Daniel J.

In: Acta Biomaterialia, Vol. 12, No. 1, 01.01.2015, p. 166-173.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Photoactivated miR-148b-nanoparticle conjugates improve closure of critical size mouse calvarial defects

AU - Qureshi, Ammar T.

AU - Doyle, Andrew

AU - Chen, Cong

AU - Coulon, Diana

AU - Dasa, Vinod

AU - DelPiero, Fabio

AU - Levi, Benjamin

AU - Monroe, W. Todd

AU - Gimble, Jeffrey M.

AU - Hayes, Daniel J.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Inducible systems providing temporal control of differentiation have the potential to improve outcomes in surgical reconstruction and regenerative medicine by precise modulation of wound healing and tissue repair processes. The aim of this study was to demonstrate that nanoformulated microRNA (miRNA) conjugates activated via photo exposure can lead to the induced osteogenic differentiation of human adipose-derived stromal/stem cells (hASCs) in vivo. The conjugate PC-miR-148b-SNP, a mimic of miRNA-148b tethered to silver nanoparticles (SNPs) via a photolabile linker, was used to modulate gene expression for improved closure of a critical size defect drilled on the right parietal bone of male CD-1 nude homozygous mice. The PC-miR-148b-SNP conjugates added to hASCs and loaded to either Matrigel or polycaprolactone (PCL) scaffolds resulted in different levels of healing of the defect. After 4 and 12 weeks, 3-D micro-computed tomography reconstructed images indicate statistically significant defect closure from 3.83 ± 1.19% to 5.46 ± 2.01% and 6.54 ± 4.28% to 32.53 ± 8.3% for non-photoactivated and photoactivated conjugates, respectively, in the PCL scaffolds. The results were confirmed with H&E and Masson's Trichrome stains in the transverse sections of photoactivated conjugates. Collagen fiber staining was greatest at 12 weeks when it reached approximately the same density and thickness as the native calvarium. This technology provides a platform that can be used with other miRNAs that actively govern the pathways responsible for regenerative and wound healing processes.

AB - Inducible systems providing temporal control of differentiation have the potential to improve outcomes in surgical reconstruction and regenerative medicine by precise modulation of wound healing and tissue repair processes. The aim of this study was to demonstrate that nanoformulated microRNA (miRNA) conjugates activated via photo exposure can lead to the induced osteogenic differentiation of human adipose-derived stromal/stem cells (hASCs) in vivo. The conjugate PC-miR-148b-SNP, a mimic of miRNA-148b tethered to silver nanoparticles (SNPs) via a photolabile linker, was used to modulate gene expression for improved closure of a critical size defect drilled on the right parietal bone of male CD-1 nude homozygous mice. The PC-miR-148b-SNP conjugates added to hASCs and loaded to either Matrigel or polycaprolactone (PCL) scaffolds resulted in different levels of healing of the defect. After 4 and 12 weeks, 3-D micro-computed tomography reconstructed images indicate statistically significant defect closure from 3.83 ± 1.19% to 5.46 ± 2.01% and 6.54 ± 4.28% to 32.53 ± 8.3% for non-photoactivated and photoactivated conjugates, respectively, in the PCL scaffolds. The results were confirmed with H&E and Masson's Trichrome stains in the transverse sections of photoactivated conjugates. Collagen fiber staining was greatest at 12 weeks when it reached approximately the same density and thickness as the native calvarium. This technology provides a platform that can be used with other miRNAs that actively govern the pathways responsible for regenerative and wound healing processes.

UR - http://www.scopus.com/inward/record.url?scp=84925161375&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925161375&partnerID=8YFLogxK

U2 - 10.1016/j.actbio.2014.10.010

DO - 10.1016/j.actbio.2014.10.010

M3 - Article

C2 - 25462528

AN - SCOPUS:84925161375

VL - 12

SP - 166

EP - 173

JO - Acta Biomaterialia

JF - Acta Biomaterialia

SN - 1742-7061

IS - 1

ER -