Size matters: Effect of granule size of the bone graft substitute (Herafill®) on bone healing using Masquelet's induced membrane in a critical size defect model in the rat's femur

J Biomed Mater Res B Appl Biomater. 2020 May;108(4):1469-1482. doi: 10.1002/jbm.b.34495. Epub 2019 Nov 13.

Abstract

The Masquelet technique for the treatment of large bone defects is a two-stage procedure based on an induced membrane. The size of a scaffold is reported to be a critical factor for bone healing response. We therefore aimed to investigate the influence of the granule size of a bone graft substitute on bone marrow derived mononuclear cells (BMC) supported bone healing in combination with the induced membrane. We compared three different sizes of Herafill® granules (Heraeus Medical GmbH, Wehrheim) with or without BMC in vivo in a rat femoral critical size defect. A 10 mm defect was made in 126 rats and a membrane induced by a PMMA-spacer. After 3 weeks, the spacer was taken out and membrane filled with different granule sizes. After 8 weeks femurs were taken for radiological, biomechanical, histological, and immunohistochemical analysis. Further, whole blood of the rat was incubated with granules and expression of 29 peptide mediators was assessed. Smallest granules showed significantly improved bone healing compared to larger granules, which however did not lead to an increased biomechanical stability in the defect zone. Small granules lead to an increased accumulation of macrophages in situ which could be assigned to the inflammatory subtype M1 by majority. Increased release of chemotactic respectively proangiogenic active factors in vitro compared to syngenic bone and beta-TCP was observed. Granule size of the bone graft substitute Herafill® has significant impact on bone healing of a critical size defect in combination with Masquelet's technique in terms of bone formation and inflammatory potential.

Keywords: Masquelet technique; bone marrow derived mononuclear cells; critical size defect; induced membrane; scaffold size.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells* / metabolism
  • Bone Marrow Cells* / pathology
  • Bone Substitutes* / chemistry
  • Bone Substitutes* / pharmacology
  • Femur* / injuries
  • Femur* / metabolism
  • Femur* / pathology
  • Male
  • Osteogenesis / drug effects*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Bone Substitutes