Antibacterial active open-porous hydroxyapatite/lysozyme scaffolds suitable as bone graft and depot for localised drug delivery

Abstract

An engineered synthetic scaffold for bone regeneration should provide temporary structural support and a medium for controlled and localised release of bioavailable medical drugs. In this work, a method is proposed to incorporate biologically active agents without impairing agent activity into open-porous resorbable hydroxyapatite scaffolds. Scaffolds are obtained by a one-pot freeze gelation process and loaded with different amounts of lysozyme, a model macromolecular drug with antibacterial activity. The antibacterial activity is tested by submerging hydroxyapatite scaffolds with 0.5 to 2.5 wt.% lysozyme into two different bacteria stock solutions. A complete dieback of M. luteus bacteria when in contact with the scaffolds is observed. Higher lysozyme amount in the scaffold leads to faster dieback. In contact with scaffolds containing 2.5 wt.% lysozyme after 30 min, no viable bacteria can be observed. An amount of 0.5 wt.% lysozyme in the scaffolds is sufficient to kill all bacteria after a contact time of 24 h. For L. innocua, a bacteriostatic effect is observed. The scaffolds have spongiosa-like stability and are suitable bone implant substitutes. As agents are released from the scaffolds by degrees over a time period of at least 9 days, they are particularly attractive as depot for localised drug delivery of bioactive macromolecular drugs.

Keywords: Antibacterial activity; bioresorption; drug delivery system; hydroxyapatite; lysozyme.