Radical scavenging of poly(methyl methacrylate) bone cement by rifampin and clinically relevant properties of the rifampin-loaded cement

Abstract

Objectives The objective of this study was to characterize the effect of rifampin incorporation into poly(methyl methacrylate) (PMMA) bone cement. While incompatibilities between the two materials have been previously noted, we sought to identify and quantify the cause of rifampin’s effects, including alterations in curing properties, mechanical strength, and residual monomer content. Methods Four cement groups were prepared using commercial PMMA bone cement: a control; one with 1 g of rifampin; and one each with equimolar amounts of ascorbic acid or hydroquinone relative to the amount of rifampin added. The handling properties, setting time, exothermic output, and monomer loss were measured throughout curing. The mechanical strength of each group was tested over 14 days. A radical scavenging assay was used to assess the scavenging abilities of rifampin and its individual moieties. Results Compared with control, the rifampin-incorporated cement had a prolonged setting time and a reduction in exothermic output during polymerization. The rifampin cement showed significantly reduced strength and was below the orthopaedic weight-bearing threshold of 70 MPa. Based on the radical scavenging assay and strength tests, the hydroquinone structure within rifampin was identified as the polymerization inhibitor. Conclusion The incorporation of rifampin into PMMA bone cement interferes with the cement’s radical polymerization. This interference is due to the hydroquinone moiety within rifampin. This combination alters the cement’s handling and curing properties, and lowers the strength below the threshold for weight-bearing applications. Additionally, the incomplete polymerization leads to increased toxic monomer output, which discourages its use even in non-weight-bearing applications. Cite this article : G. A. Funk, E. M. Menuey, K. A. Cole, T. P. Schuman, K. V. Kilway, T. E. McIff. Radical scavenging of poly(methyl methacrylate) bone cement by rifampin and clinically relevant properties of the rifampin-loaded cement. Bone Joint Res 2019;8:81–89. DOI: 10.1302/2046-3758.82.BJR-2018-0170.R2.

Elution of rifampin and vancomycin from a weight-bearing silorane-based bone cement

“…In fact, the incorporation of rifampin into PMMA cement leads to a 500% increase in leaching of MMA over 24 hours, potentially further exacerbating these effects. 12 Due to the aforementioned limitations, alternatives to PMMA, such as calcium-based ceramics, have been evaluated for use in spine and other orthopaedic applications. While these alternative cements avoid the cytotoxicity associated with PMMA and offer other benefits such as bioabsorbability and osteoconductive properties, they are associated with other disadvantages including decreased biomechanical strength, poor handling characteristics, and prolonged curing times.…”

“…The mechanism for rifampin inhibition of PMMA polymerization has been proposed, but the mechanism leading to attenuated elution is not yet defined. 12 We have previously speculated that rifampin may become chemically bound to polymerizing PMMA during its radical scavenging process, leading to low elution. Therefore, much of the incorporated drug would be bound to the PMMA matrix and unable to escape.…”

“… 10 , 11 A recent study found that rifampin acts as a radical scavenger during PMMA’s radical polymerization. 12 The hydroquinone moiety behaves as a radical trap and inhibits cement polymerization, resulting in the cement having a prolonged curing time, reduced mechanical strength, and increased release of unreacted MMA monomer.…”

Adjuvant antibiotic‐loaded bone cement: Concerns with current use and research to make it work

“…Liposome‐formulated antifungals have been shown to increase the elution compared to formulation with a solubilizing agent, without some of the reported compromises in mechanical properties that other antibiotic formulations are known to induce 48 . Antibiotic loading through liposomes theoretically could enable the delivery of lipophilic drugs that are currently considered incompatible with PMMA, such as the radical‐scavenging rifampin 49 …”

Progress of antibiotic-loaded bone cement in joint arthroplasty

“…When rifampin is added, PMMA showed a serious reduction in compressive strength, with a prolonged setting time, decreased exothermic output in the curing process, and an increase in toxicity due to MMA monomer release, indicating incomplete polymerization. [ 44 ]…”