Comprehensive genetic analysis of early host body reactions to the bioactive and bio-inert porous scaffolds

PLoS One. 2014 Jan 14;9(1):e85132. doi: 10.1371/journal.pone.0085132. eCollection 2014.

Abstract

To design scaffolds for tissue regeneration, details of the host body reaction to the scaffolds must be studied. Host body reactions have been investigated mainly by immunohistological observations for a long time. Despite of recent dramatic development in genetic analysis technologies, genetically comprehensive changes in host body reactions are hardly studied. There is no information about host body reactions that can predict successful tissue regeneration in the future. In the present study, porous polyethylene scaffolds were coated with bioactive collagen or bio-inert poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB) and were implanted subcutaneously and compared the host body reaction to those substrates by normalizing the result using control non-coat polyethylene scaffold. The comprehensive analyses of early host body reactions to the scaffolds were carried out using a DNA microarray assay. Within numerous genes which were expressed differently among these scaffolds, particular genes related to inflammation, wound healing, and angiogenesis were focused upon. Interleukin (IL)-1β and IL-10 are important cytokines in tissue responses to biomaterials because IL-1β promotes both inflammation and wound healing and IL-10 suppresses both of them. IL-1β was up-regulated in the collagen-coated scaffold. Collagen-specifically up-regulated genes contained both M1- and M2-macrophage-related genes. Marked vessel formation in the collagen-coated scaffold was occurred in accordance with the up-regulation of many angiogenesis-inducible factors. The DNA microarray assay provided global information regarding the host body reaction. Interestingly, several up-regulated genes were detected even on the very bio-inert PMB-coated surfaces and those genes include inflammation-suppressive and wound healing-suppressive IL-10, suggesting that not only active tissue response but also the inert response may relates to these genetic regulations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / adverse effects*
  • Biocompatible Materials / chemistry
  • Cell Movement / drug effects
  • Collagen / adverse effects*
  • Collagen / chemistry
  • Gene Expression Regulation / drug effects*
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Materials Testing / methods*
  • Methacrylates / adverse effects*
  • Methacrylates / chemistry
  • Mice
  • Mice, Inbred C57BL
  • Phosphorylcholine / adverse effects
  • Phosphorylcholine / analogs & derivatives*
  • Phosphorylcholine / chemistry
  • Polyethylene / chemistry
  • Porosity
  • Surface Properties
  • Time Factors
  • Tissue Engineering
  • Tissue Scaffolds / adverse effects*
  • Tissue Scaffolds / chemistry

Substances

  • Biocompatible Materials
  • Methacrylates
  • Phosphorylcholine
  • poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate)
  • Polyethylene
  • Collagen

Grants and funding

This work was supported by Core Research Evolutional Science and Technology (CREST; http://www.jst.go.jp/crest/nanoif/english/index.html) and Grant-in-Aid for Scientific Research on Innovation Areas (20106014; http://www.jsps.go.jp/english/e-grants/index.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.