Sustained presentation of BMP-2 enhances osteogenic differentiation of human adipose-derived stem cells in gelatin hydrogels

J Biomed Mater Res A. 2016 Jun;104(6):1387-97. doi: 10.1002/jbm.a.35668. Epub 2016 Feb 18.

Abstract

Human adipose-derived stem cells (hASCs) show great potential for healing bone defects. Bone morphogenetic protein-2 (BMP-2) has been reported to stimulate their osteogenic differentiation both in vitro and in vivo. Here, methacrylated gelatin (GelMA) hydrogels were evaluated as a system to deliver BMP-2 to encapsulated hASCs from two different donors, and BMP-2 delivered from the hydrogels was compared to BMP-2 presented exogenously in culture media. GelMA hydrogels were shown to provide sustained, localized presentation of BMP-2 due to electrostatic interactions between the growth factor and biomaterial after an initial burst release. Both donors exhibited similar responses to the loaded and exogenous growth factor; BMP-2 from the hydrogels had a statistically significant effect on hASC osteogenic differentiation compared to exogenous BMP-2. Expression of alkaline phosphatase was accelerated, and cells in hydrogels with loaded BMP-2 deposited more calcium at one, two, and four weeks than cells without BMP-2 or with the growth factor presented in the media. There were no statistically significant differences in calcium content between groups with 25, 50, or 100 µg/mL loaded BMP-2, suggesting that using a lower growth factor dose may be as effective as a higher loading amount in this system. Taken together, these findings suggest that controlled delivery of BMP-2 from the GelMA enhances its osteogenic bioactivity compared to free growth factor presented in the media. Thus, the GelMA system is a promising biomaterial for BMP-2-mediated hASC osteogenesis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1387-1397, 2016.

Keywords: biomaterials; bone tissue engineering; drug delivery; gelatin methacrylate; growth factor.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adipose Tissue / cytology*
  • Alkaline Phosphatase / metabolism
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Calcium / analysis
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • DNA / analysis
  • Gelatin / pharmacology*
  • Humans
  • Hydrogels / pharmacology*
  • Osteogenesis / drug effects*
  • Recombinant Proteins / pharmacology
  • Staining and Labeling
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Bone Morphogenetic Protein 2
  • Hydrogels
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • Gelatin
  • DNA
  • Alkaline Phosphatase
  • Calcium