Osteoinductive Effects of Free and Immobilized Bone Forming Peptide-1 on Human Adipose-Derived Stem Cells

PLoS One. 2016 Mar 1;11(3):e0150294. doi: 10.1371/journal.pone.0150294. eCollection 2016.

Abstract

Most synthetic polymeric materials currently used for bone tissue engineering lack specific signals through which cells can identify and interact with the surface, resulting in incompatibility and compromised osteogenic activity. Soluble inductive factors also have issues including a short half-live in vivo. Bone forming peptide-1 is a truncated peptide from the immature form of bone morphogenetic protein-7 (BMP-7) that displays higher osteogenic activity than full-length, mature BMP-7. In this study, we used a mussel-inspired immobilization strategy mediated by polymerization of dopamine to introduce recently discovered stimulators of bone forming peptide-1 (BFP-1) onto the surface of poly-lactic-co-glycolic acid (PLGA) substrate to form a biomaterial that overcomes these challenges. Human adipose-derived stem cells (hASCs), being abundant and easy accessible, were used to test the osteogenic activity of BFP-1 and the novel biomaterial. Under osteoinductive conditions, cells treated with both BFP-1 alone and BFP-1-coated biomaterials displayed elevated expression of the osteogenic markers alkaline phosphatase (ALP), osteocalcin (OC), and RUNX2. Furthermore, hASCs associated with poly-dopamine-assisted BFP-1-immobilized PLGA (pDA-BFP-1-PLGA) scaffolds promoted in vivo bone formation in nude mice. Our novel materials may hold great promise for future bone tissue engineering applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Morphogenetic Protein 7 / chemistry
  • Bone Morphogenetic Protein 7 / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Adhesion / genetics
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Humans
  • Immunohistochemistry
  • Lactic Acid / chemistry
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Models, Animal
  • Osteocalcin / genetics
  • Osteocalcin / metabolism
  • Osteogenesis / drug effects*
  • Osteogenesis / genetics
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / cytology
  • Stem Cells / drug effects*
  • Stem Cells / metabolism
  • Tissue Engineering / methods
  • Tissue Scaffolds / chemistry

Substances

  • Bone Morphogenetic Protein 7
  • Core Binding Factor Alpha 1 Subunit
  • Peptide Fragments
  • bone forming peptide-1
  • Osteocalcin
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Alkaline Phosphatase

Grants and funding

This work was supported by the National Natural Science Foundation of China (2011/81170937 to YZhou, 2013/81400484 to YG), (http://www.nsfc.gov.cn/Portal0/default152.htm) and the Program for New Century Excellent Talents in University from Ministry of Education of China (NCET-11-0026 to YZhou), (http://www.moe.edu.cn/publicfiles/business/htmlfiles/moe/A16/index.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.