Linking the Transcriptional Landscape of Bone Induction to Biomaterial Design Parameters

Nathalie Groen, Huipin Yuan, Dennie G. A. J. Hebels, Gulistan Kocer, Faustin Mbuyi, Vanessa LaPointe, Roman Truckenmuller, Clemens A. van Blitterswijk, Pamela Habibovic, Jan de Boer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

New engineering possibilities allow biomaterials to serve as active orchestrators of the molecular and cellular events of tissue regeneration. Here, the molecular control of tissue regeneration for calcium phosphate (CaP)-based materials is established by defining the parameters critical for tissue induction and those are linked to the molecular circuitry controlling cell physiology. The material properties (microporosity, ion composition, protein adsorption) of a set of synthesized osteoinductive and noninductive CaP ceramics are parameterized and these properties are correlated to a transcriptomics profile of osteogenic cells grown on the materials in vitro. Using these data, a genetic network controlling biomaterial-induced bone formation is built. By isolating the complex material properties into single-parameter test conditions, it is verified that a subset of these genes is indeed controlled by surface topography and ions released from the ceramics, respectively. The gene network points to a decisive role for extracellular matrix deposition in osteoinduction by genes such as tenascin C and hyaluronic acid synthase 2, which are controlled by calcium and phosphate ions as well as surface topography. This work provides insight into the biomaterial composition and material engineering aspects of bone void filling and can be used as a strategy to explore the interface between biomaterials and tissue regeneration.

Original languageEnglish
Article number1603259
Number of pages14
JournalAdvanced Materials
Volume29
Issue number10
DOIs
Publication statusPublished - 14 Mar 2017

Keywords

  • CALCIUM-PHOSPHATE CERAMICS
  • MESENCHYMAL STROMAL CELLS
  • OSTEOGENIC DIFFERENTIATION
  • MORPHOGENETIC PROTEIN-2
  • STEM-CELLS
  • PHASE-COMPOSITION
  • TISSUE
  • OSTEOINDUCTION
  • DISCOVERY
  • PATHWAY

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