Polydopamine-assisted osteoinductive peptide immobilization of polymer scaffolds for enhanced bone regeneration by human adipose-derived stem cells

Eunkyung Ko, Kisuk Yang, Jisoo Shin, Seung-Woo Cho

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

Immobilization of osteoinductive molecules, including growth factors or peptides, on polymer scaffolds is critical for improving stem cell-mediated bone tissue engineering. Such molecules provide osteogenesis-stimulating signals for stem cells. Typical methods used for polymeric scaffold modification (e.g., chemical conjugation or physical adsorption), however, have limitations (e.g., multistep, complicated procedures, material denaturation, batch-to-batch inconsistency, and inadequate conjugation) that diminish the overall efficiency of the process. Therefore, in this study, we report a biologically inspired strategy to prepare functional polymer scaffolds that efficiently regulate the osteogenic differentiation of human adipose-derived stem cells (hADSCs). Polymerization of dopamine (DA), a repeated motif observed in mussel adhesive protein, under alkaline pH conditions, allows for coating of a polydopamine (pDA) layer onto polymer scaffolds. Our study demonstrates that predeposition of a pDA layer facilitates highly efficient, simple immobilization of peptides derived from osteogenic growth factor (bone morphogenetic protein-2; BMP-2) on poly(lactic-co-glycolic acid) (PLGA) scaffolds via catechol chemistry. The BMP-2 peptide-immobilized PLGA scaffolds greatly enhanced in vitro osteogenic differentiation and calcium mineralization of hADSCs using either osteogenic medium or nonosteogenic medium. Furthermore, transplantation of hADSCs using pDA-BMP-2-PLGA scaffolds significantly promoted in vivo bone formation in critical-sized calvarial bone defects. Therefore, pDA-mediated catechol functionalization would be a simple and effective method for developing tissue engineering scaffolds exhibiting enhanced osteoinductivity. To the best of our knowledge, this is the first study demonstrating that pDA-mediated surface modification of polymer scaffolds potentiates the regenerative capacity of human stem cells for healing tissue defect in vivo.

Original languageEnglish
Pages (from-to)3202-3213
Number of pages12
JournalBiomacromolecules
Volume14
Issue number9
DOIs
Publication statusPublished - 2013 Sep 9

Fingerprint

Scaffolds (biology)
Stem cells
Scaffolds
Peptides
Polymers
Bone
Tissue engineering
Acids
Proteins
Functional polymers
Intercellular Signaling Peptides and Proteins
Defects
Denaturation
Molecules
Chemical modification
Tissue Scaffolds
Bone Morphogenetic Protein 2
Surface treatment
polydopamine
Calcium

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Materials Chemistry
  • Polymers and Plastics
  • Biomaterials

Cite this

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abstract = "Immobilization of osteoinductive molecules, including growth factors or peptides, on polymer scaffolds is critical for improving stem cell-mediated bone tissue engineering. Such molecules provide osteogenesis-stimulating signals for stem cells. Typical methods used for polymeric scaffold modification (e.g., chemical conjugation or physical adsorption), however, have limitations (e.g., multistep, complicated procedures, material denaturation, batch-to-batch inconsistency, and inadequate conjugation) that diminish the overall efficiency of the process. Therefore, in this study, we report a biologically inspired strategy to prepare functional polymer scaffolds that efficiently regulate the osteogenic differentiation of human adipose-derived stem cells (hADSCs). Polymerization of dopamine (DA), a repeated motif observed in mussel adhesive protein, under alkaline pH conditions, allows for coating of a polydopamine (pDA) layer onto polymer scaffolds. Our study demonstrates that predeposition of a pDA layer facilitates highly efficient, simple immobilization of peptides derived from osteogenic growth factor (bone morphogenetic protein-2; BMP-2) on poly(lactic-co-glycolic acid) (PLGA) scaffolds via catechol chemistry. The BMP-2 peptide-immobilized PLGA scaffolds greatly enhanced in vitro osteogenic differentiation and calcium mineralization of hADSCs using either osteogenic medium or nonosteogenic medium. Furthermore, transplantation of hADSCs using pDA-BMP-2-PLGA scaffolds significantly promoted in vivo bone formation in critical-sized calvarial bone defects. Therefore, pDA-mediated catechol functionalization would be a simple and effective method for developing tissue engineering scaffolds exhibiting enhanced osteoinductivity. To the best of our knowledge, this is the first study demonstrating that pDA-mediated surface modification of polymer scaffolds potentiates the regenerative capacity of human stem cells for healing tissue defect in vivo.",
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Polydopamine-assisted osteoinductive peptide immobilization of polymer scaffolds for enhanced bone regeneration by human adipose-derived stem cells. / Ko, Eunkyung; Yang, Kisuk; Shin, Jisoo; Cho, Seung-Woo.

In: Biomacromolecules, Vol. 14, No. 9, 09.09.2013, p. 3202-3213.

Research output: Contribution to journalArticle

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AU - Yang, Kisuk

AU - Shin, Jisoo

AU - Cho, Seung-Woo

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