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Related Experiment Video

Updated: Jun 11, 2025

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Incorporating Microbial Stimuli for Osteogenesis in a Rabbit Posterolateral Spinal Fusion Model.

Nada Ristya Rahmani1,2, Anneli Duits1, Michiel Croes1

  • 1Department of Orthopedics, University Medical Centre Utrecht, Utrecht, The Netherlands.

Tissue Engineering. Part A
|September 30, 2024
PubMed
Summary

Bacille Calmette-Guérin (BCG) incorporated into biphasic calcium phosphate (BCP) ceramics showed potential for stimulating bone formation in spinal fusion models. This suggests carefully selected microbial stimuli can enhance synthetic bone graft alternatives.

Keywords:
bacteriabone regenerative medicineceramicfungimycobacteriumosteoimmunomodulation

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Area of Science:

  • Biomaterials Science
  • Immunology
  • Orthopedic Surgery

Background:

  • Autologous bone grafts are limited in supply, creating a need for effective bone graft substitutes.
  • Synthetic ceramics lack inherent biological activity for bone regeneration.
  • Incorporating immunomodulatory agents into ceramics is a strategy to enhance bone formation.

Purpose of the Study:

  • To investigate the potential of microbial stimuli to enhance bone formation in synthetic bone graft materials.
  • To evaluate the efficacy of three microbial stimuli (BCG, gamma-irradiated *Staphylococcus aureus*, gamma-irradiated *Candida albicans*) integrated into biphasic calcium phosphate (BCP) ceramics.

Main Methods:

  • BCP ceramic constructs were prepared with three different microbial stimuli: Bacille Calmette-Guérin (BCG), gamma-irradiated *Staphylococcus aureus* (γi-*S. aureus*), and gamma-irradiated *Candida albicans* (γi-*C. Albicans*).
  • Constructs were implanted in rabbit posterolateral spinal fusion (PLF) and intramuscular models for 10 weeks.
  • Bone formation was assessed using manual palpation, micro computed tomography, and histology.

Main Results:

  • The BCG-loaded BCP showed the most promise in the PLF model, with increased manual stiffness and nearly double the bone volume compared to controls (9% vs. 4.6%).
  • Gamma-irradiated *S. aureus* and *C. albicans* appeared to inhibit bone formation in the PLF model (1.4% and 1.2% bone area, respectively).
  • No significant bone induction was observed in any of the intramuscular implants across all groups.

Conclusions:

  • Incorporating specific immunomodulatory agents into ceramic bone substitutes can modulate bone formation.
  • The clinically approved BCG demonstrated promising results for enhancing bone regeneration in a spinal fusion model.
  • Further research is warranted to explore the clinical translation of BCG-enhanced ceramic bone grafts.