Vancomycin Containing PLLA/β-TCP Controls MRSA In Vitro

Abstract

Osteomyelitis caused by Methicillin-resistant Staphylococcus aureus (MRSA) often requires surgery and prolonged systemic antibiotic treatment. Local antibiotic delivery systems of bioceramics or polymers have been developed to treat osteomyelitis. A disadvantage of biodegradable polymers is the initial burst of antibiotics into the environment; one advantage of bioceramics is its osteoconductivity. We therefore developed a vancomycin-containing poly-l-lactic acid/β-tricalcium phosphate (PLLA/β-TCP) composite to control antibiotic release and stimulate bone formation. We (1) characterized these composites, (2) assessed vancomycin release in inhibitory doses, and (3) determined whether they would permit cell adhesion, proliferation, and mineralization in vitro. We molded 250 vancomycin-containing (VC) and 125 vancomycin-free (VUC) composites using PLLA, β-TCP, and chloroform. One hundred twenty-five VC composites were further dip-coated with PLLA (CVC) to delay antibiotic release. Composites were characterized according to their pore structure, size, volume, density, and surface area. Vancomycin release and bioactivity were determined. Adhesion, proliferation, and mineralization were assessed for two and three replicates on Days 3 and 7 with mesenchymal stem (MSC) and Saos type 2 cells. Pore size, volume, apparent density, and surface area of the CVC were 3.5 ± 1.9 μm, 0.005 ± 0.002 cm(3)/g, 1.18 g/cm(3) and 3.68 m(2)/g, respectively. CVC released 1.71 ± 0.13 mg (63.1%) and 2.49 ± 0.64 mg (91.9%) of its vancomycin on Day 1 and Week 6, respectively. MSC and Saos type 2 cells attached and proliferated on composites on Days 3 and 7. Vancomycin-containing PLLA/β-TCP composites release antibiotics in inhibitory doses after dip coating and appeared biocompatible based on adhesion, proliferation, and mineralization. Vancomycin-containing PLLA/β-TCP composites may be useful for controlling MRSA but will require in vivo confirmation.