In vivo tissue response and antibacterial efficacy of minocycline delivery system based on polymethylmethacrylate bone cement

Abstract

This study aims the in vivo biological characterization of an innovative minocycline delivery system, based on polymethylmethacrylate bone cement. Bone cements containing 1% or 2.5% (w/w) minocycline were formulated and evaluated through solid-state characterization. Biological evaluation was conducted in vivo, within a rat model, following the subcutaneous and bone tissue implantation, and tissue implantation associated with Staphylococcus aureus is challenging. The assessment of the tissue/biomaterial interaction was conducted by histologic, histomorphometric and microtomographic techniques. Minocycline addition to the composition of the polymethylmethacrylate bone cement did not modify significantly the cement properties. Drug release profile was marked by an initial burst release followed by a low-dosage sustained release. Following the subcutaneous tissue implantation, a reduced immune-inflammatory reaction was verified, with diminished cell recruitment and a thinner fibro-connective capsule formation. Minocycline-releasing cements were found to enhance the bone-to-implant contact and bone tissue formation, following the tibial implantation. Lastly, an effective antibacterial activity was mediated by the implanted cement following the tissue challenging with S. aureus. Kinetic minocycline release profile, attained with the developed polymethylmethacrylate system, modulated adequately the in vivo biological response, lessening the immune-inflammatory activation and enhancing bone tissue formation. Also, an effective in vivo antibacterial activity was established. These findings highlight the adequacy and putative application of the developed system for orthopedic applications.

Encapsulated bacteriophages in alginate-nanohydroxyapatite hydrogel as a novel delivery system to prevent orthopedic implant-associated infections

“…9,29 However, limited antimicrobial diffusion, sub-therapeutic levels of antimicrobial agent, dose-dependent antimicrobial activity, antimicrobials' toxicity, and the spread of antibiotic-resistant bacteria, underscore the need for new approaches to control these bacterial infections. 6,7,9,30 In this study, a new drug-delivery system based on encapsulated phages on Alg-nanoHA hydrogels was assessed as a multifunctional approach. This system has three components with specific and complementary functionalities: 1) Alg hydrogel is responsible for transporting and delivering the therapeutic agents to the local target, 2) osteo-regeneration stimulation is endorsed by the presence of bioactive and osteoconductive nanoHA, and, 3) prevention of bacterial colonization and proliferation is addressed by the local delivery of phages.…”

“…The experiment was approved by the Local Ethics Committee and the national regulatory entity -Direção Geral de Alimentação e Veterinária (DGAV), observing the technical standards of protection for experimental animals, according to both policies and principles of laboratory animal care and with the European Union guidelines (European Directive 2010/63/EU and National Decree-Law 113/2013). Housing, anesthesia, and post-operative care were performed according to Silva et al 7 Sixteen New Zealand white rabbits, 18 weeks old and weighing between 3700-3900 g, were used for the subcutaneous implantation of the phages-loaded hydrogels. Briefly, a cutaneous incision (about 3 cm long) was performed in the dorsal region for the implantation of hydrogels following blunt subcutaneous dissection.…”

“…[3][4][5] Local strategies as vehicles for antimicrobial agents delivery has emerged as an adjunct in the prevention and treatment of bone graft-related infections. 3,[6][7][8] Local delivery systems show advantages over systemic approaches, such as drug delivery at or close to the infection site, increased efficacy and bioavailability of the antimicrobial agent, dose reduction and decreased systemic toxicity risks. 8 However, some limitations are associated to these systems, namely delivery of sub-therapeutic antimicrobial levels, favoring bacterial resistance development; limited antimicrobial diffusion into the peri-implant tissues; dose-dependent antimicrobial activity, and potential cytotoxicity of the antimicrobial agents.…”

Assessment of the Bone Healing Process Mediated by Periosteum-Derived Mesenchymal Stem Cells’ Secretome and a Xenogenic Bioceramic—An In Vivo Study in the Rabbit Critical Size Calvarial Defect Model

“…For reducing noise smoothing, ring artifacts and beam hardening tools were used and set at 2, 8, and 40%, respectively. Reconstructed images were evaluated with DataViewer software (version 1.5.6.2; Bruker, Bruker microCT NV, Kontig, Belgium) to place the cortical surface of the calvaria perpendicular to the long axis of the ROI to allow the analysis of the bone volume (BV) and graft volume (GV) ratios within the total volume (TV), defined within the margins of the defect, as previously described [29]. Images were loaded in CTAn software (version 1.17.7.2; Bruker microCT NV, Kontig, Belgium) for subsequent evaluation.…”

Suppressing Antibacterial Resistance: Chemical Binding of Monolayer Quaternary Ammonium Salts to Polymethyl Methacrylate in an Aqueous Solution and Its Clinical Efficacy

“…Polymethyl methacrylate (PMMA) and its composites are the predominant biomaterials used for indwelling devices, which are loaded with antibiotics or disinfectants as a standard procedure for antibacterial treatment [11,12]. Like other biomaterials, PMMA carries the risk of microbial colonization and infection.…”