Mineralization of peptide amphiphile nanofibers and its effect on the differentiation of human mesenchymal stem cells

Timothy D. Sargeant, Conrado Aparicio, Joshua E. Goldberger, Honggang Cui, Samuel I Stupp

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

One of the important targets in regenerative medicine is to design resorbable materials that can promote formation of new bone in large skeletal defects. One approach to this challenge is to use a bioactive and biodegradable organic matrix that can promote cellular adhesion and direct differentiation. We have here studied matrices composed of peptide amphiphiles (PAs) that self-assemble into nanofibers and create self-supporting gels under cell culture conditions. The bioactivity of PAs was designed by incorporating in their peptide sequences phosphoserine residues, to promote hydroxyapatite formation in the culture medium, and the cell adhesion epitope RGDS. In osteogenic medium supplemented with calcium the PA nanofibers were found to nucleate spheroidal nanoparticles of crystalline carbonated hydroxyapatite approximately 100 nm in diameter. This mineralization mode is not epitaxial relative to the long axis of the nanofibers and occurs in the presence of serine or phosphoserine residues in the peptide sequence of the amphiphiles. Mixing of the phosphoserine- containing PAs with 5 wt.% RGDS-containing PA molecules does not inhibit formation of the mineral nanoparticles. Quantitative real time reverse transcription polymerase chain reaction and immunohistochemistry analysis for alkaline phosphatase (ALP) and osteopontin expression suggest that these mineralized matrices promote osteogenic differentiation of human mesenchymal stem cells. Based on ALP expression, the presence of phosphoserine residues in PA nanofibers seems to favor osteogenic differentiation.

Original languageEnglish
Pages (from-to)2456-2465
Number of pages10
JournalActa Biomaterialia
Volume8
Issue number7
DOIs
Publication statusPublished - Jul 2012

Fingerprint

Nanofibers
Amphiphiles
Stem cells
Mesenchymal Stromal Cells
Peptides
Phosphoserine
Durapatite
Phosphatases
Nanoparticles
Alkaline Phosphatase
Hydroxyapatite
Cell culture
arginyl-glycyl-aspartyl-serine
Osteopontin
Regenerative Medicine
Epitopes
Polymerase chain reaction
Cell adhesion
Osteogenesis
Cell Adhesion

Keywords

  • Bone
  • Phosphoserine
  • Regenerative medicine
  • Self-assembly
  • Tissue engineering

ASJC Scopus subject areas

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

Cite this

Mineralization of peptide amphiphile nanofibers and its effect on the differentiation of human mesenchymal stem cells. / Sargeant, Timothy D.; Aparicio, Conrado; Goldberger, Joshua E.; Cui, Honggang; Stupp, Samuel I.

In: Acta Biomaterialia, Vol. 8, No. 7, 07.2012, p. 2456-2465.

Research output: Contribution to journalArticle

Sargeant, Timothy D. ; Aparicio, Conrado ; Goldberger, Joshua E. ; Cui, Honggang ; Stupp, Samuel I. / Mineralization of peptide amphiphile nanofibers and its effect on the differentiation of human mesenchymal stem cells. In: Acta Biomaterialia. 2012 ; Vol. 8, No. 7. pp. 2456-2465.
@article{71e69d376f9c4fbb814ef5a08dd3fc7e,
title = "Mineralization of peptide amphiphile nanofibers and its effect on the differentiation of human mesenchymal stem cells",
abstract = "One of the important targets in regenerative medicine is to design resorbable materials that can promote formation of new bone in large skeletal defects. One approach to this challenge is to use a bioactive and biodegradable organic matrix that can promote cellular adhesion and direct differentiation. We have here studied matrices composed of peptide amphiphiles (PAs) that self-assemble into nanofibers and create self-supporting gels under cell culture conditions. The bioactivity of PAs was designed by incorporating in their peptide sequences phosphoserine residues, to promote hydroxyapatite formation in the culture medium, and the cell adhesion epitope RGDS. In osteogenic medium supplemented with calcium the PA nanofibers were found to nucleate spheroidal nanoparticles of crystalline carbonated hydroxyapatite approximately 100 nm in diameter. This mineralization mode is not epitaxial relative to the long axis of the nanofibers and occurs in the presence of serine or phosphoserine residues in the peptide sequence of the amphiphiles. Mixing of the phosphoserine- containing PAs with 5 wt.{\%} RGDS-containing PA molecules does not inhibit formation of the mineral nanoparticles. Quantitative real time reverse transcription polymerase chain reaction and immunohistochemistry analysis for alkaline phosphatase (ALP) and osteopontin expression suggest that these mineralized matrices promote osteogenic differentiation of human mesenchymal stem cells. Based on ALP expression, the presence of phosphoserine residues in PA nanofibers seems to favor osteogenic differentiation.",
keywords = "Bone, Phosphoserine, Regenerative medicine, Self-assembly, Tissue engineering",
author = "Sargeant, {Timothy D.} and Conrado Aparicio and Goldberger, {Joshua E.} and Honggang Cui and Stupp, {Samuel I}",
year = "2012",
month = "7",
doi = "10.1016/j.actbio.2012.03.026",
language = "English",
volume = "8",
pages = "2456--2465",
journal = "Acta Biomaterialia",
issn = "1742-7061",
publisher = "Elsevier BV",
number = "7",

}

TY - JOUR

T1 - Mineralization of peptide amphiphile nanofibers and its effect on the differentiation of human mesenchymal stem cells

AU - Sargeant, Timothy D.

AU - Aparicio, Conrado

AU - Goldberger, Joshua E.

AU - Cui, Honggang

AU - Stupp, Samuel I

PY - 2012/7

Y1 - 2012/7

N2 - One of the important targets in regenerative medicine is to design resorbable materials that can promote formation of new bone in large skeletal defects. One approach to this challenge is to use a bioactive and biodegradable organic matrix that can promote cellular adhesion and direct differentiation. We have here studied matrices composed of peptide amphiphiles (PAs) that self-assemble into nanofibers and create self-supporting gels under cell culture conditions. The bioactivity of PAs was designed by incorporating in their peptide sequences phosphoserine residues, to promote hydroxyapatite formation in the culture medium, and the cell adhesion epitope RGDS. In osteogenic medium supplemented with calcium the PA nanofibers were found to nucleate spheroidal nanoparticles of crystalline carbonated hydroxyapatite approximately 100 nm in diameter. This mineralization mode is not epitaxial relative to the long axis of the nanofibers and occurs in the presence of serine or phosphoserine residues in the peptide sequence of the amphiphiles. Mixing of the phosphoserine- containing PAs with 5 wt.% RGDS-containing PA molecules does not inhibit formation of the mineral nanoparticles. Quantitative real time reverse transcription polymerase chain reaction and immunohistochemistry analysis for alkaline phosphatase (ALP) and osteopontin expression suggest that these mineralized matrices promote osteogenic differentiation of human mesenchymal stem cells. Based on ALP expression, the presence of phosphoserine residues in PA nanofibers seems to favor osteogenic differentiation.

AB - One of the important targets in regenerative medicine is to design resorbable materials that can promote formation of new bone in large skeletal defects. One approach to this challenge is to use a bioactive and biodegradable organic matrix that can promote cellular adhesion and direct differentiation. We have here studied matrices composed of peptide amphiphiles (PAs) that self-assemble into nanofibers and create self-supporting gels under cell culture conditions. The bioactivity of PAs was designed by incorporating in their peptide sequences phosphoserine residues, to promote hydroxyapatite formation in the culture medium, and the cell adhesion epitope RGDS. In osteogenic medium supplemented with calcium the PA nanofibers were found to nucleate spheroidal nanoparticles of crystalline carbonated hydroxyapatite approximately 100 nm in diameter. This mineralization mode is not epitaxial relative to the long axis of the nanofibers and occurs in the presence of serine or phosphoserine residues in the peptide sequence of the amphiphiles. Mixing of the phosphoserine- containing PAs with 5 wt.% RGDS-containing PA molecules does not inhibit formation of the mineral nanoparticles. Quantitative real time reverse transcription polymerase chain reaction and immunohistochemistry analysis for alkaline phosphatase (ALP) and osteopontin expression suggest that these mineralized matrices promote osteogenic differentiation of human mesenchymal stem cells. Based on ALP expression, the presence of phosphoserine residues in PA nanofibers seems to favor osteogenic differentiation.

KW - Bone

KW - Phosphoserine

KW - Regenerative medicine

KW - Self-assembly

KW - Tissue engineering

UR - http://www.scopus.com/inward/record.url?scp=84861629589&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84861629589&partnerID=8YFLogxK

U2 - 10.1016/j.actbio.2012.03.026

DO - 10.1016/j.actbio.2012.03.026

M3 - Article

VL - 8

SP - 2456

EP - 2465

JO - Acta Biomaterialia

JF - Acta Biomaterialia

SN - 1742-7061

IS - 7

ER -