Osteoblastic differentiation of human bone marrow stromal cells in self-assembled BMP-2 receptor-binding peptide-amphiphiles

Jue Yeon Lee, Jung Eun Choo, Young Suk Choi, Jin Sook Suh, Seung Jin Lee, Chong Pyoung Chung, Yoon Jeong Park

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Self-assembled nanostructures consisting of BMP receptor-binding peptides, termed osteopromotive domains (OPDs), and hydrophobic alkyl chains were fabricated with the aim of developing three-dimensional scaffolding materials for osteoblastic differentiation. OPD peptide was identified from BMP-2 and had an affinity for BMP receptors thereby inducing differentiation of human bone marrow stromal cells into osteoblastic cells. The peptide-hydrophobic alkyl chain amphiphiles were designed to mimic nanofibrous extracellular structures and to add osteogenic ligands to enhance osteoblastic cell function. The OPD peptide-amphiphiles (OPDAs) that end with the alkylation of the N-terminus of the OPD peptide were synthesized by standard solid phase chemistry. The self-assembly was triggered by mixing OPDA solution with calcium ions. Observation using scanning electron microscopy (SEM) revealed the formation of nanofibrous structures with extremely high aspect ratios and high surface areas. The FT-IR and circular dichroism (CD) spectrophotometry demonstrated that self-assembled nanofibers have a β-sheet structure. The activation of Smad, an osteoblastic differentiation marker, was obtained in the cell culture gel of self-assembled OPDA; therefore, the intracellular signal transduction for osteogenesis was performed like an OPD peptide. Cell survival was supported in the OPDA gel for 10 days, and osteoblastic differentiation of human bone marrow stromal cells (hBMSCs) was evident as demonstrated by calcein staining and ALP activity measurement. These results revealed that self-assembled OPDA maintained osteogenic activity by the surface-exposed OPD peptide. Taken together, the self-assembled OPDA nanofibrous gel can be utilized as a cell culture scaffold in bone regeneration.

Original languageEnglish
Pages (from-to)3532-3541
Number of pages10
JournalBiomaterials
Volume30
Issue number21
DOIs
StatePublished - Jul 2009

Keywords

  • BMP-2
  • Nanofibers
  • Osteoblastic differentiation
  • Osteopromotive domain (OPD)
  • Peptide-amphiphiles
  • Scaffold

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