Microbiological and pharmacological tests on new antibiotic-loaded PMMA-based composites for the treatment of

Gianluca Giavaresi1, Elisa Bertazzoni Minelli, Maria Sartori

  • 1Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute IRCCS, via di Barbiano 1/10, 40136, Bologna, Italy. gianluca.giavaresi@ior.it

Insights

New antibiotic-eluting polymethyl methacrylate (PMMA) composite nails effectively treated osteomyelitis in rabbits. The gentamicin and vancomycin combination demonstrated synergistic effects, clearing infection and showing sustained antibiotic release in bone.

Area of Science:

  • Biomaterials Science
  • Orthopedic Surgery
  • Infectious Diseases

Background:

  • Osteomyelitis is a challenging bone infection requiring effective treatment strategies.
  • Local antibiotic delivery systems aim to achieve high drug concentrations at the infection site while minimizing systemic toxicity.
  • Polymethyl methacrylate (PMMA)-based composites offer potential for controlled antibiotic release in orthopedic applications.

Purpose of the Study:

  • To evaluate the local antibiotic diffusion and efficacy of novel PMMA-based nail-shaped composites loaded with gentamicin and vancomycin for treating osteomyelitis.
  • To compare the performance of two composite formulations: one enriched with β-tricalcium phosphate (P-TCP) and BaSO(4), and another with only BaSO(4) (P-BaSO(4)).
  • To assess the resolution of infection and quantify antibiotic penetration into bone tissue in a rabbit femur model.

Main Methods:

  • Two types of PMMA composite nails (P-TCP and P-BaSO(4)) were prepared and soaked in a gentamicin (G) and vancomycin (V) solution.
  • Nails were implanted into the intramedullary cavity of healthy and Staphylococcus aureus-infected rabbit femurs.
  • Infection resolution was assessed using microbiological, pharmacological, and histological analyses (including Smeltzer score).

Main Results:

  • A significant progression of osteomyelitis was observed in untreated infected femurs.
  • Animals treated with antibiotic-loaded nails showed complete resolution of infection, with no bacteria detected via microbiology and histology.
  • Both gentamicin and vancomycin were released promptly and sustained for at least 3 weeks in bone tissue.
  • The P-TCP composite demonstrated higher antibiotic release compared to the P-BaSO(4) composite.
  • The combination of gentamicin and vancomycin exhibited a synergistic bactericidal effect in vivo.

Conclusions:

  • Porous PMMA composite nails loaded with gentamicin and vancomycin are effective drug delivery systems for treating osteomyelitis.
  • The P-TCP composite formulation facilitates superior antibiotic release compared to the P-BaSO(4) formulation.
  • The in vivo synergistic action of gentamicin and vancomycin provides a potent therapeutic strategy against bone infections.

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