title: The effect of the antimicrobial peptide, Dhvar-5, on gentamicin release from a polymethyl methacrylate bone cement.
abstract: The objective of this study was to investigate the release mechanism and kinetics of the antimicrobial peptide, Dhvar-5, both alone and in combination with gentamicin, from a standard commercial polymethyl methacrylate (PMMA) bone cement. Different amounts of Dhvar-5 were mixed with the bone cement powders of Osteopal and the gentamicin-containing Osteopal G bone cement and their release kinetics from the polymerized cement were investigated. Additionally, the internal structure of the bone cements were analysed by scanning electron microscopy (SEM) of the fracture surfaces. Secondly, porosity was investigated with the mercury intrusion method and related to the observed release profiles. In order to obtain an insight into the mechanical characteristics of the bone cement mixtures, the compressive strength of Osteopal and Osteopal G with Dhvar-5 was also investigated. The total Dhvar-5 release reached 96% in the 100 mg Dhvar-5/g Osteopal cement, whereas total gentamicin release from Osteopal G reached only 18%. Total gentamicin release increased significantly to 67% with the addition of 50mg Dhvar-5/g, but the Dhvar-5 release was not influenced. SEM showed an increase of dissolved gentamicin crystals with the addition of Dhvar-5. The mercury intrusion results suggested an increase of small pores (< 0.1 microm) with the addition of Dhvar-5. Compressive strength of Osteopal was reduced by the addition of Dhvar-5 and gentamicin, but still remained above the limit prescribed by the ISO standard for clinical bone cements. We therefore conclude that the antimicrobial peptide, Dhvar-5, was released in high amounts from PMMA bone cement. When used together with gentamicin sulphate, Dhvar-5 made the gentamicin crystals accessible for the release medium presumably through increased micro-porosity (< 0.1 microm) resulting in a fourfold increase of gentamicin release.
authors.affiliation: Department of Orthopaedic Surgery, VU University Medical Center (VUmc),Vrije Universiteit, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Faber
authors.forename: R J W
authors.initials: RJ
authors.lastname: Hoogendoorn
authors.forename: D M
authors.initials: DM
authors.lastname: Lyaruu
authors.forename: H P
authors.initials: HP
authors.lastname: Stallmann
authors.forename: J
authors.initials: J
authors.lastname: van Marle
authors.forename: A
authors.initials: A
authors.lastname: van Nieuw Amerongen
authors.forename: T H
authors.initials: TH
authors.lastname: Smit
authors.forename: P I J M
authors.initials: PI
authors.lastname: Wuisman
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry; D001843:Bone Cements / Q000032:analysis / Q000737:chemistry*; D020099:Coated Materials, Biocompatible; D019245:Compressive Strength; D003692:Delayed-Action Preparations / Q000032:analysis / Q000737:chemistry*; D004058:Diffusion; D005839:Gentamicins / Q000008:administration & dosage / Q000737:chemistry*; D054808:Histatins; D008422:Materials Testing; D019904:Polymethyl Methacrylate / Q000008:administration & dosage / Q000737:chemistry*; D012471:Salivary Proteins and Peptides / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry*
chemical_list: D023181:Antimicrobial Cationic Peptides; D001843:Bone Cements; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; C504850:Dhvar-5; D005839:Gentamicins; D054808:Histatins; D012471:Salivary Proteins and Peptides; D019904:Polymethyl Methacrylate