Abstract

Prophylactic antibiotic bone cements are extensively used in orthopaedics. However, the development of antimicrobial resistance to antibiotics, demonstrates a need to find alternative treatments. Herein, an antimicrobial honey (SurgihoneyRO-SHRO) has been successfully incorporated into a calcium sulphate (CS) based cement to produce a hard tissue scaffold with the ability to inhibit bacterial growth. Antimicrobial properties elicited from SHRO are predominantly owed to the water-initiated production of reactive oxygen species (ROS). As an alternative to initially loading CS cement with SHRO, in order to prevent premature activation, SHRO was added into the already developing cement matrix, locking available water into the CS crystal structure before SHRO addition. Promisingly, this methodology produced > 2.5 times (715.0 ± 147.3 μM/mL/g) more ROS over 24 h and exhibited a compressive strength (32.2 ± 5.8 MPa) comparable to trabecular bone after 3 weeks of immersion. In-vitro the SHRO loaded CS scaffolds were shown to inhibit growth of clinically relevant organisms, Staphylococcus aureus and Pseudomonas aeruginosa, with comparable potency to equivalent doses of gentamicin. Encouragingly, formulations did not inhibit wound healing or induce an inflammatory response from osteoblasts. Overall this study highlights the prophylactic potential of CS-SHRO cements as an alternative to traditional antibiotics.

Highlights

  • Prophylactic antibiotic bone cements are extensively used in orthopaedics

  • Production of CS_Control, CS_SHRO1 and CS_SHRO2 cements with a L:P ratio of 0.2 mL/g resulted in workable pastes that could be transferred to a split mould and produce cylindrical test specimens

  • If the calcium sulphate hemihydrate ­(CaSO4·0.5H2O) cement was left to harden for 4 min prior to the addition of SHRO (CS_SHRO2), initial (20 min) and final (30 min) setting times were extended to a lesser extent than for CS_SHRO1

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Summary

Introduction

Prophylactic antibiotic bone cements are extensively used in orthopaedics. the development of antimicrobial resistance to antibiotics, demonstrates a need to find alternative treatments. As an alternative to initially loading CS cement with SHRO, in order to prevent premature activation, SHRO was added into the already developing cement matrix, locking available water into the CS crystal structure before SHRO addition This methodology produced > 2.5 times (715.0 ± 147.3 μM/mL/g) more ROS over 24 h and exhibited a compressive strength (32.2 ± 5.8 MPa) comparable to trabecular bone after 3 weeks of immersion. It is essential that these materials are well tolerated by the body (i.e. biocompatible), resorbed at a rate that matches bone formation, cost-effective, stored and easy to apply within the clinical setting To this end, there has been a vast emergence of calcium-salt based cement systems in recent ­decades[1]. The development of novel antimicrobials that provide a viable alternative to commonly used prophylactics, as well as systems by which to enable efficacious delivery, are a healthcare p­ riority[9,12]

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