Chitosan and chitosan oligosaccharides in antibiotic-loaded bone cement

Orthopedic infections can be treated with antibiotic-loaded bone cements. However, due to the growing number of resistances, new formulations are needed to e.g. improve the drug release. For this reason, dual-antibiotic bone cement containing chitosan and chitosan oligosaccharide was prepared in the presented study.

INFLUENCE OF CHITOSAN AND CHITOSAN OLIGOSACCHARIDES ON DUAL-ANTIBIOTIC-LOADED BONE CEMENT: IN VITRO EVALUATION

Tantavisut S, Leanpolchareanchai J, Wongrakpanich A (2022) Influence of chitosan and chitosan oligosaccharide on dual antibiotic-loaded bone cement: In vitro evaluations. PLoS ONE 17(11): e0276604. https://doi.org/10.1371/journal.pone.0276604

Bone cements made from materials such as polymethaacrylate (PMMA) play an important role in the treatment of orthopedic infections such as joint prosthesis infections or chronic osteomyelitis. Here, bone cements are loaded with antibiotics and inserted into the infected area in the form of beads or as spacers. To enhance the effect of these, more than one antibiotic is often used to achieve a synergistic effect. In addition, the larger amount of antibiotic causes a more porous surface, increasing the contact surface between body fluid and bone cement and further increasing the effect.

However, due to the growing number of antibiotic resistances, alternatives are needed to maintain efficacy. Besides antimicrobial substances e.g. silver nanoparticles, pyrogens like glucose, xylitol or lactose are of great interest to improve the effect by increasing the porosity. In particular, chitosan (CS) and its derivatives, such as chitosan oligosaccharide (CSO) show great potential. They are biodegradable and biocompatible. Due to their biodegradation, they increase the porosity of the bone cement. In addition, both CS and CSO have antibacterial and antifungal effects. However, no studies on the pharmaceutical and mechanical effects of chitosans in bone cement have been made so far.

Therefore, in the presented paper, the effect of CS (DDA: 97.46 %, MW: ∼25 kDa) and CSO (DDA: 87.79 %, MW: ≤ 5 kDa) in premixed dual-antibiotic bone cement was investigated (Copal1 G+V). The antibiotic release profiles, bacterial activity and mechanical properties of different antibiotic-loaded bone cements (ALBC) were compared.

RESULTS

• Successful fabrication of bone cements, no significant differences in diameter, thickness and weight of control (bone cement only), CS and CSO bone cements
• Comparing 10 % CS and 10 % CSO, the bone cements with CSO had higher porosity, however, there was no significant change in weight after immersion in PBS
• Increased release of vancomycin after 48 h with 10 % CS and 10 % CSO compared to control
• No significant difference between the gentamicin release profiles of the control group and that of the CS group (CS 1 %, CS 5 %, and CS 10 %), but significantly increased release for CSO between 72 h and 7 days compared to the control group
• There was a lower release of gentamicin in all bone cement samples compared to vancomycin
• All bone cement samples were able to inhibit the growth of aureus and methicillin-resistant S. aureus
• No evidence of cytotoxicity on Saos-2 cells after 24 h incubation
• Surface roughness of bone cement increased with increasing amount of CS, no differences between CSO and control group

Conclusions: In the presented study, it was shown that the addition of CS and CSO can improve the drug release of e.g. antibiotics in bone cement. ChO 10% was the best bone cement formulation with high drug release, good biocompatibility and acceptable mechanical properties, showing good efficacy against orthopedic pathogens such as S. aureus. However, overall, further in vitro and in vivo experiments are required before it can be used in the clinic.

Link to article: Influence of chitosan and chitosan oligosaccharide on dual antibiotic-loaded bone cement: In vitro evaluations | PLOS ONE