Modification of the Polymer of a Bone Cement with Biodegradable Microspheres of PLGA and Loading with Daptomycin and Vancomycin Improve the Response to Bone Tissue Infection.

Joaquin García-García,Sara Ruíz-Díez,Cielo García-Montero,Basilio De La Torre,Oscar Fraile-Martinez,Melchor Álvarez-Mon,Miguel A Ortega,Natalio García-Honduvilla,Miguel Angel Álvarez-Mon,Galo Azuara,Julia Buján

doi:10.3390/polym14050888

Abstract

Chronic infections are one of the most serious adverse outcomes of prosthetic surgery. Prosthetic revision surgery using a bone cement loaded with antibiotics between the two stages of the surgery is commonly performed. However, this method often fails to reach the minimum inhibitory concentration and promotes antibiotic resistance, thus emphasizing the need for improving the current available therapies. Materials and methods: In this study, we performed a study of the in vivo response of a polymer-based construct of poly (lactic-co-glycolic acid) (PLGA) in the solid phase of Palacos R® in combination with vancomycin, daptomycin, and/or linezolid. To test its effectiveness, we applied an in vivo model, using both histological and immunohistochemical analyses to study the bone tissue. Results: The presence of PLGA in the combination of vancomycin with daptomycin showed the most promising results regarding the preservation of bone cytoarchitecture and S. aureus elimination. Conversely, the combination of vancomycin plus linezolid was associated with a loss of bone cytoarchitecture, probably related to an increased macrophage response and inefficient antimicrobial activity. Conclusions: The modification of Palacos R® bone cement with PLGA microspheres and its doping with the antibiotic daptomycin in combination with vancomycin improve the tissue response to bone infection.

Highlights

The presence of many cocci adhering to the rod after extraction from the suspension was observed by scanning electron microscopy [16]. This rod became the implant contaminated with methicillinresistant S. aureus (MRSA) that we introduced into the bone tissue of the rabbit [16,17]
In the comparative analysis between groups with Palacos R® cement and with Palacos R cement + poly(lactic-co-glycolic acid) (PLGA), the presence of PLGA significantly improved the preservation of bone architecture when the combination of antibiotics used was vancomycin with daptomycin (Group 5)
Palacos R + PLGA bone cement loaded with vancomycin and linezolid (Group 6) induced severe destruction of the bone architecture, so treatment with linezolid in combination with vancomycin did not preserve the bone histoarchitecture (Figures 1 and 2)

Summary

Introduction

Prosthetic revision surgery performed in two stages has been the most commonly used method, using a bone cement spacer between the first and second stages [4,5]. This bone cement spacer is loaded with antibiotics, whose release results in much higher local concentrations than can be achieved through intravenous injection. This release is higher in the first few days but persists up to several weeks, in many cases at concentrations below the minimum inhibitory concentration (MIC) of the microbe, which has been associated with the development of antibiotic resistance, the colonization of spacers, and, therapeutic failure [6,7]

Methods

Results

Discussion

Conclusion