Heterobifunctional poly(ethylene glycol)-tethered bone morphogenetic protein-2-stimulated bone marrow mesenchymal stromal cell differentiation and osteogenesis

Hsia W. Liu, Chih H. Chen, Ching L. Tsai, I. Hsuan Lin, Ging H. Hsiue

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

We describe a biomimetic mode of insoluble signaling stimulation to provide target delivery of bone morphogenetic protein-2 (BMP-2), with the aim of prolonging the retention of BMP-2 use in bone tissue engineering and to enable its localized release in response to cellular activity. In our novel localization process, we used heterobifunctional acrylate-N-hydroxysuccinimide poly(ethylcne glycol) (PEG) as a spacer to tether BMP-2 onto a poly(lactide-co-glycolide) scaffold. Use of PEG-tethered BMP-2 was feasible because BMP-2 retained its activity after covalent conjugation. The PEG-tethered BMP-2 conjugate sustained stimulation and retained its mitogenic activity, notably affecting pluripotent stem cell proliferation and differentiation. We seeded the scaffolds with bone marrow-derived mesenchymal stromal cells as progenitor cells to evaluate their morphology and phenotypic expression. We also created bilateral, full-thickness cranial defects in rabbits to investigate the osteogenic effect of cultured mesenchymal stromal cells on bone regeneration in vivo. Histomorphometry and histology demonstrated that the PEG-tethered BMP-2 conjugate enhanced de novo bone formation after surgery. Our work revealed the potential for biomimetic surface engineering by entrapping signaling growth factor to stimulate osteogenesis. Our technique may provide a new platform for bone-engineered stem cell therapies.

Original languageEnglish
Pages (from-to)1113-1124
Number of pages12
JournalTissue Engineering
Volume13
Issue number5
DOIs
Publication statusPublished - May 2007
Externally publishedYes

Fingerprint

Bone Morphogenetic Protein 2
Ethylene Glycol
Mesenchymal Stromal Cells
Osteogenesis
Polyethylene glycols
Cell Differentiation
Bone
Proteins
Biomimetics
Stem Cells
Polyglactin 910
Bone and Bones
Pluripotent Stem Cells
Scaffolds (biology)
Bone Regeneration
Glycols
Stem cells
Tissue Engineering
Cell- and Tissue-Based Therapy
Intercellular Signaling Peptides and Proteins

ASJC Scopus subject areas

  • Biophysics
  • Biotechnology
  • Cell Biology

Cite this

Heterobifunctional poly(ethylene glycol)-tethered bone morphogenetic protein-2-stimulated bone marrow mesenchymal stromal cell differentiation and osteogenesis. / Liu, Hsia W.; Chen, Chih H.; Tsai, Ching L.; Lin, I. Hsuan; Hsiue, Ging H.

In: Tissue Engineering, Vol. 13, No. 5, 05.2007, p. 1113-1124.

Research output: Contribution to journalArticle

@article{b7bc1bef38a84cdc8a2a3414710406a3,
title = "Heterobifunctional poly(ethylene glycol)-tethered bone morphogenetic protein-2-stimulated bone marrow mesenchymal stromal cell differentiation and osteogenesis",
abstract = "We describe a biomimetic mode of insoluble signaling stimulation to provide target delivery of bone morphogenetic protein-2 (BMP-2), with the aim of prolonging the retention of BMP-2 use in bone tissue engineering and to enable its localized release in response to cellular activity. In our novel localization process, we used heterobifunctional acrylate-N-hydroxysuccinimide poly(ethylcne glycol) (PEG) as a spacer to tether BMP-2 onto a poly(lactide-co-glycolide) scaffold. Use of PEG-tethered BMP-2 was feasible because BMP-2 retained its activity after covalent conjugation. The PEG-tethered BMP-2 conjugate sustained stimulation and retained its mitogenic activity, notably affecting pluripotent stem cell proliferation and differentiation. We seeded the scaffolds with bone marrow-derived mesenchymal stromal cells as progenitor cells to evaluate their morphology and phenotypic expression. We also created bilateral, full-thickness cranial defects in rabbits to investigate the osteogenic effect of cultured mesenchymal stromal cells on bone regeneration in vivo. Histomorphometry and histology demonstrated that the PEG-tethered BMP-2 conjugate enhanced de novo bone formation after surgery. Our work revealed the potential for biomimetic surface engineering by entrapping signaling growth factor to stimulate osteogenesis. Our technique may provide a new platform for bone-engineered stem cell therapies.",
author = "Liu, {Hsia W.} and Chen, {Chih H.} and Tsai, {Ching L.} and Lin, {I. Hsuan} and Hsiue, {Ging H.}",
year = "2007",
month = "5",
doi = "10.1089/ten.2006.0209",
language = "English",
volume = "13",
pages = "1113--1124",
journal = "Tissue Engineering",
issn = "1076-3279",
publisher = "Mary Ann Liebert Inc.",
number = "5",

}

TY - JOUR

T1 - Heterobifunctional poly(ethylene glycol)-tethered bone morphogenetic protein-2-stimulated bone marrow mesenchymal stromal cell differentiation and osteogenesis

AU - Liu, Hsia W.

AU - Chen, Chih H.

AU - Tsai, Ching L.

AU - Lin, I. Hsuan

AU - Hsiue, Ging H.

PY - 2007/5

Y1 - 2007/5

N2 - We describe a biomimetic mode of insoluble signaling stimulation to provide target delivery of bone morphogenetic protein-2 (BMP-2), with the aim of prolonging the retention of BMP-2 use in bone tissue engineering and to enable its localized release in response to cellular activity. In our novel localization process, we used heterobifunctional acrylate-N-hydroxysuccinimide poly(ethylcne glycol) (PEG) as a spacer to tether BMP-2 onto a poly(lactide-co-glycolide) scaffold. Use of PEG-tethered BMP-2 was feasible because BMP-2 retained its activity after covalent conjugation. The PEG-tethered BMP-2 conjugate sustained stimulation and retained its mitogenic activity, notably affecting pluripotent stem cell proliferation and differentiation. We seeded the scaffolds with bone marrow-derived mesenchymal stromal cells as progenitor cells to evaluate their morphology and phenotypic expression. We also created bilateral, full-thickness cranial defects in rabbits to investigate the osteogenic effect of cultured mesenchymal stromal cells on bone regeneration in vivo. Histomorphometry and histology demonstrated that the PEG-tethered BMP-2 conjugate enhanced de novo bone formation after surgery. Our work revealed the potential for biomimetic surface engineering by entrapping signaling growth factor to stimulate osteogenesis. Our technique may provide a new platform for bone-engineered stem cell therapies.

AB - We describe a biomimetic mode of insoluble signaling stimulation to provide target delivery of bone morphogenetic protein-2 (BMP-2), with the aim of prolonging the retention of BMP-2 use in bone tissue engineering and to enable its localized release in response to cellular activity. In our novel localization process, we used heterobifunctional acrylate-N-hydroxysuccinimide poly(ethylcne glycol) (PEG) as a spacer to tether BMP-2 onto a poly(lactide-co-glycolide) scaffold. Use of PEG-tethered BMP-2 was feasible because BMP-2 retained its activity after covalent conjugation. The PEG-tethered BMP-2 conjugate sustained stimulation and retained its mitogenic activity, notably affecting pluripotent stem cell proliferation and differentiation. We seeded the scaffolds with bone marrow-derived mesenchymal stromal cells as progenitor cells to evaluate their morphology and phenotypic expression. We also created bilateral, full-thickness cranial defects in rabbits to investigate the osteogenic effect of cultured mesenchymal stromal cells on bone regeneration in vivo. Histomorphometry and histology demonstrated that the PEG-tethered BMP-2 conjugate enhanced de novo bone formation after surgery. Our work revealed the potential for biomimetic surface engineering by entrapping signaling growth factor to stimulate osteogenesis. Our technique may provide a new platform for bone-engineered stem cell therapies.

UR - http://www.scopus.com/inward/record.url?scp=34249894420&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34249894420&partnerID=8YFLogxK

U2 - 10.1089/ten.2006.0209

DO - 10.1089/ten.2006.0209

M3 - Article

VL - 13

SP - 1113

EP - 1124

JO - Tissue Engineering

JF - Tissue Engineering

SN - 1076-3279

IS - 5

ER -