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Published on: January 2, 2014
Vancomycin containing PLLA/β-TCP controls MRSA in vitro
Berna Kankilic1, Erdal Bayramli, Emine Kilic
1Department of Biotechnology, Middle East Technical University, Medical Center, 100 Yil, Ankara 06531, Turkey.
Background:
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.
Questions/Purposes:
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.
Methods:
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.
Results:
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.
Conclusions:
Vancomycin-containing PLLA/β-TCP composites release antibiotics in inhibitory doses after dip coating and appeared biocompatible based on adhesion, proliferation, and mineralization.
Clinical Relevance:
Vancomycin-containing PLLA/β-TCP composites may be useful for controlling MRSA but will require in vivo confirmation.
Insights
This study developed a vancomycin-infused composite material for treating bone infections. The material effectively released antibiotics and supported cell growth, showing promise for future clinical applications.
Area of Science:
- Biomaterials Science
- Orthopedic Surgery
- Infectious Diseases
Background:
- Osteomyelitis caused by Methicillin-resistant Staphylococcus aureus (MRSA) presents significant treatment challenges, often necessitating surgical intervention and extended antibiotic therapy.
- Current local antibiotic delivery systems utilize bioceramics or polymers, each with distinct advantages and disadvantages regarding antibiotic release and bone integration.
- A novel vancomycin-loaded poly-l-lactic acid/β-tricalcium phosphate (PLLA/β-TCP) composite was engineered to optimize antibiotic elution and promote bone regeneration.
Purpose of the Study:
- To characterize the physical properties and antibiotic release profile of the developed vancomycin-containing PLLA/β-TCP composite.
- To evaluate the in vitro biocompatibility of the composite, specifically its capacity to support cell adhesion, proliferation, and mineralization.
- To assess the efficacy of the composite in delivering vancomycin at inhibitory concentrations against MRSA.
Main Methods:
- Vancomycin-containing (VC) and vancomycin-free (VUC) composites were fabricated using PLLA, β-TCP, and chloroform, with some VC composites further dip-coated with PLLA (CVC) to modulate release.
- Composite characteristics including pore structure, size, volume, density, and surface area were meticulously analyzed.
- In vitro assessments included vancomycin release kinetics, bioactivity assays, and evaluation of mesenchymal stem cell (MSC) and Saos type 2 cell adhesion, proliferation, and mineralization.
Main Results:
- The dip-coated CVC composites exhibited specific pore characteristics (3.5 ± 1.9 μm), volume, density, and surface area.
- Controlled vancomycin release was observed, with 63.1% released on Day 1 and 91.9% by Week 6.
- Mesenchymal stem cells and Saos type 2 cells demonstrated successful adhesion and proliferation on the composite materials within 3 and 7 days.
Conclusions:
- The vancomycin-containing PLLA/β-TCP composites, particularly after dip-coating, effectively release antibiotics in inhibitory concentrations.
- The composite materials demonstrated biocompatibility, supporting crucial cellular functions like adhesion, proliferation, and mineralization in vitro.
- These findings suggest that vancomycin-loaded PLLA/β-TCP composites hold potential for managing MRSA osteomyelitis, warranting further in vivo validation.
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