BMP-2 peptide-functionalized nanopatterned substrates for enhanced osteogenic differentiation of human mesenchymal stem cells

Mun Jung Kim; Bora Lee; Kisuk Yang; Junyong Park; Seokwoo Jeon; Soong Ho Um; Dong Ik Kim; Sung Gap Im; Seung Woo Cho

doi:10.1016/j.biomaterials.2013.06.019

BMP-2 peptide-functionalized nanopatterned substrates for enhanced osteogenic differentiation of human mesenchymal stem cells

Mun Jung Kim, Bora Lee, Kisuk Yang, Junyong Park, Seokwoo Jeon, Soong Ho Um, Dong Ik Kim, Sung Gap Im, Seung Woo Cho

Research output: Contribution to journal › Article › peer-review

101 Citations (Scopus)

Abstract

A variety of biophysical and biochemical factors control stem cell differentiation. In this study, we developed a nanopatterned substrate platform to surface immobilize osteoinductive bone morphogenetic protein-2 (BMP-2) peptides. Specifically, polyurethane acrylate (PUA) substrates with nanometer-scale groove- and dot-shaped topography were fabricated. The nanopatterned PUA surface was uniformly coated with poly(glycidyl methacrylate) (pGMA) by initiated chemical vapor deposition (iCVD) followed by covalent immobilization of BMP-2 peptides. This approach resulted in much more efficient BMP-2 peptide immobilization than physical adsorption. The combined effects of biochemical signals from BMP-2 peptides and nanotopographical stimulation on osteogenic differentiation of hMSCs were examined in culture with and without soluble osteogenic factors. Results of Alizarin Red S staining, immunostaining, and quantitative real-time polymerase chain reaction revealed that hMSCs cultured on nanopatterned surfaces with immobilized BMP-2 peptides exhibited greater potential for osteogenic differentiation than hMSCs on a flat surface. Furthermore, the nanopatterned substrates with BMP-2 peptides directed osteogenic differentiation of hMSCs even without osteogenesis soluble inducing factors. Substrates with nanotopography and bioactive signals that induce differentiation of stem cells towards specific lineages could be used to develop functional stem cell culture substrates and tissue engineered scaffolds for therapeutic applications.

Original language	English
Pages (from-to)	7236-7246
Number of pages	11
Journal	Biomaterials
Volume	34
Issue number	30
DOIs	https://doi.org/10.1016/j.biomaterials.2013.06.019
Publication status	Published - 2013 Oct

Bibliographical note

Funding Information:
This work was supported by a grant ( 2010-0022037 ) funded by the National Research Foundation of Korea , the Ministry of Education, Science and Technology, Republic of Korea. This work was also supported by a grant ( A110552 ) from the Korea Health Technology R&D Project of the Ministry of Health & Welfare of the Republic of Korea. This work was supported by the Advanced Biomass R&D Center (ABC) of the Global Frontier Project funded by the Ministry of Education, Science and Technology ( ABC-2011-0031356 ), and by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology ( 2012-0003282 ).

All Science Journal Classification (ASJC) codes

Biophysics
Bioengineering
Ceramics and Composites
Biomaterials
Mechanics of Materials

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10.1016/j.biomaterials.2013.06.019

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title = "BMP-2 peptide-functionalized nanopatterned substrates for enhanced osteogenic differentiation of human mesenchymal stem cells",

abstract = "A variety of biophysical and biochemical factors control stem cell differentiation. In this study, we developed a nanopatterned substrate platform to surface immobilize osteoinductive bone morphogenetic protein-2 (BMP-2) peptides. Specifically, polyurethane acrylate (PUA) substrates with nanometer-scale groove- and dot-shaped topography were fabricated. The nanopatterned PUA surface was uniformly coated with poly(glycidyl methacrylate) (pGMA) by initiated chemical vapor deposition (iCVD) followed by covalent immobilization of BMP-2 peptides. This approach resulted in much more efficient BMP-2 peptide immobilization than physical adsorption. The combined effects of biochemical signals from BMP-2 peptides and nanotopographical stimulation on osteogenic differentiation of hMSCs were examined in culture with and without soluble osteogenic factors. Results of Alizarin Red S staining, immunostaining, and quantitative real-time polymerase chain reaction revealed that hMSCs cultured on nanopatterned surfaces with immobilized BMP-2 peptides exhibited greater potential for osteogenic differentiation than hMSCs on a flat surface. Furthermore, the nanopatterned substrates with BMP-2 peptides directed osteogenic differentiation of hMSCs even without osteogenesis soluble inducing factors. Substrates with nanotopography and bioactive signals that induce differentiation of stem cells towards specific lineages could be used to develop functional stem cell culture substrates and tissue engineered scaffolds for therapeutic applications.",

author = "Kim, {Mun Jung} and Bora Lee and Kisuk Yang and Junyong Park and Seokwoo Jeon and Um, {Soong Ho} and Kim, {Dong Ik} and Im, {Sung Gap} and Cho, {Seung Woo}",

note = "Funding Information: This work was supported by a grant ( 2010-0022037 ) funded by the National Research Foundation of Korea , the Ministry of Education, Science and Technology, Republic of Korea. This work was also supported by a grant ( A110552 ) from the Korea Health Technology R&D Project of the Ministry of Health & Welfare of the Republic of Korea. This work was supported by the Advanced Biomass R&D Center (ABC) of the Global Frontier Project funded by the Ministry of Education, Science and Technology ( ABC-2011-0031356 ), and by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology ( 2012-0003282 ).",

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T1 - BMP-2 peptide-functionalized nanopatterned substrates for enhanced osteogenic differentiation of human mesenchymal stem cells

AU - Kim, Mun Jung

AU - Lee, Bora

AU - Yang, Kisuk

AU - Park, Junyong

AU - Jeon, Seokwoo

AU - Um, Soong Ho

AU - Kim, Dong Ik

AU - Im, Sung Gap

AU - Cho, Seung Woo

N1 - Funding Information: This work was supported by a grant ( 2010-0022037 ) funded by the National Research Foundation of Korea , the Ministry of Education, Science and Technology, Republic of Korea. This work was also supported by a grant ( A110552 ) from the Korea Health Technology R&D Project of the Ministry of Health & Welfare of the Republic of Korea. This work was supported by the Advanced Biomass R&D Center (ABC) of the Global Frontier Project funded by the Ministry of Education, Science and Technology ( ABC-2011-0031356 ), and by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology ( 2012-0003282 ).

PY - 2013/10

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N2 - A variety of biophysical and biochemical factors control stem cell differentiation. In this study, we developed a nanopatterned substrate platform to surface immobilize osteoinductive bone morphogenetic protein-2 (BMP-2) peptides. Specifically, polyurethane acrylate (PUA) substrates with nanometer-scale groove- and dot-shaped topography were fabricated. The nanopatterned PUA surface was uniformly coated with poly(glycidyl methacrylate) (pGMA) by initiated chemical vapor deposition (iCVD) followed by covalent immobilization of BMP-2 peptides. This approach resulted in much more efficient BMP-2 peptide immobilization than physical adsorption. The combined effects of biochemical signals from BMP-2 peptides and nanotopographical stimulation on osteogenic differentiation of hMSCs were examined in culture with and without soluble osteogenic factors. Results of Alizarin Red S staining, immunostaining, and quantitative real-time polymerase chain reaction revealed that hMSCs cultured on nanopatterned surfaces with immobilized BMP-2 peptides exhibited greater potential for osteogenic differentiation than hMSCs on a flat surface. Furthermore, the nanopatterned substrates with BMP-2 peptides directed osteogenic differentiation of hMSCs even without osteogenesis soluble inducing factors. Substrates with nanotopography and bioactive signals that induce differentiation of stem cells towards specific lineages could be used to develop functional stem cell culture substrates and tissue engineered scaffolds for therapeutic applications.

AB - A variety of biophysical and biochemical factors control stem cell differentiation. In this study, we developed a nanopatterned substrate platform to surface immobilize osteoinductive bone morphogenetic protein-2 (BMP-2) peptides. Specifically, polyurethane acrylate (PUA) substrates with nanometer-scale groove- and dot-shaped topography were fabricated. The nanopatterned PUA surface was uniformly coated with poly(glycidyl methacrylate) (pGMA) by initiated chemical vapor deposition (iCVD) followed by covalent immobilization of BMP-2 peptides. This approach resulted in much more efficient BMP-2 peptide immobilization than physical adsorption. The combined effects of biochemical signals from BMP-2 peptides and nanotopographical stimulation on osteogenic differentiation of hMSCs were examined in culture with and without soluble osteogenic factors. Results of Alizarin Red S staining, immunostaining, and quantitative real-time polymerase chain reaction revealed that hMSCs cultured on nanopatterned surfaces with immobilized BMP-2 peptides exhibited greater potential for osteogenic differentiation than hMSCs on a flat surface. Furthermore, the nanopatterned substrates with BMP-2 peptides directed osteogenic differentiation of hMSCs even without osteogenesis soluble inducing factors. Substrates with nanotopography and bioactive signals that induce differentiation of stem cells towards specific lineages could be used to develop functional stem cell culture substrates and tissue engineered scaffolds for therapeutic applications.

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BMP-2 peptide-functionalized nanopatterned substrates for enhanced osteogenic differentiation of human mesenchymal stem cells

Abstract

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