LOCAL INDUCTION OF INFLAMMATION AFFECTS BONE FORMATION

M. Croes, M. C. Kruyt, L. Loozen, A. H. M. Kragten, H. Yuan, W. J. Dhert, F. C. Oner, J. Alblas*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Web of Science)

Abstract

To explore the influence of inflammatory processes on bone formation, we applied a new in vivo screening model. Confined biological pockets were first created in rabbits as a response to implanted bone cement discs. These biomembrane pockets were subsequently used to study the effects of inflammatory stimuli on ectopic bone formation within biphasic calcium phosphate (BCP) constructs loaded with TNF-alpha, lipopolysaccharide (LPS) or lipoteichoic acid (LTA), all with or without bone morphogenetic protein (BMP)-2. Analysis of bone formation after 12 weeks demonstrated that the inflammatory mediators were not bone-inductive in combination with the BCP alone, but inhibited or enhanced BMP-induced bone formation. LPS was associated with a strong inhibition of bone formation by BMP-2, while LTA and TNF-alpha showed a positive interaction with BMP-2. Since the biomembrane pockets did not interfere with bone formation and prevented the leakage of pro-inflammatory compounds to the surrounding tissue, the biomembrane model can be used for in vivo approaches to study local inflammation in conjunction with new bone formation. Using this model, it was shown that the modulation of the inflammatory response could be beneficial or detrimental to the subsequent bone formation process. The co-delivery of inflammatory factors and bone-related growth factors should be further explored as a strategy to enhance the bone-forming efficacy of bone substitutes.

Original languageEnglish
Pages (from-to)211-226
Number of pages16
JournalEuropean Cells & Materials
Volume33
DOIs
Publication statusPublished - 2017

Keywords

  • osteoimmunology
  • bone regeneration
  • inflammation
  • bone morphogenetic protein
  • tumour necrosis factor alpha
  • lipopolysaccharide
  • lipoteichoic acid
  • rabbit
  • MESENCHYMAL STEM-CELLS
  • NECROSIS-FACTOR-ALPHA
  • ILIAC CREST AUTOGRAFT
  • TOLL-LIKE RECEPTORS
  • OSTEOGENIC DIFFERENTIATION
  • GROWTH-FACTORS
  • TNF-ALPHA
  • HETEROTOPIC OSSIFICATION
  • TISSUE REGENERATION
  • INDUCED MEMBRANES

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