In vitro and in vivo drug release and antibacterial properties of the novel vancomycin-loaded bone-like hydroxyapatite/poly amino acid scaffold

Abstract

Antibiotic-loaded carriers were developed to fill cavities and locally deliver antibiotics following implantation. However, the most commonly used antibiotic carrier, polymethyl methacrylate (PMMA), has many disadvantages including that it does not promote bone regeneration or conduction. Vancomycin-loaded bone-like hydroxyapatite/poly amino acid (V-BHA/PAA) was successfully fabricated by a homogeneous method, certified as biosafe and known to promote osteogenesis. To evaluate its drug-release features, the quantity of the vancomycin in the elution was obtained every 2 days after in vitro simulated body fluid immersion. The drug concentration in the elution was determined to obtain the drug-release curve. The in vitro drug release was a three-phase process with two release peaks. Its antibacterial activity was evaluated in vitro using an antibacterial zone assay, antibacterial inhibition, and scanning electron microscopy (SEM) observation. Scaffolds of V-BHA/PAA were implanted into a rabbit model of chronic osteomyelitis. The antibacterial activity of the material was evaluated in vivo by gross observations, X-ray, and histological and ultrastructural observations. During the first 48 h, the vancomycin release was more rapid, followed by a period of sustained slow release. Use of V-BHA/PAA could achieve relatively long-term vancomycin delivery of 38 days in vitro and 42 days in vivo. V-BHA/PAA showed a significant and consistent bactericidal effect toward both Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) in vitro and in vivo. Moreover, the bactericidal effect was stronger than that of vancomycin-loaded polymethyl meth acrylate (V-PMMA). The duration of the antibacterial effect of V-BHA/PAA toward both S. aureus and MRSA exceeded 28 days in vitro, while that of V-PMMA lasted only 14 days. The curative rate for V-BHA/PAA in the chronic osteomyelitis model was 75% for regular S. aureus and 66.67% for MRSA infection, which significantly exceeded that of V-PMMA (50% and 41.67%, respectively). Vancomycin released from the V-BHA/PAA scaffold was significantly superior to that delivered by V-PMMA.

Developments in Antibiotic-Eluting Scaffolds for the Treatment of Osteomyelitis

“…The choice of drug is also guided by the clinical context. For example, in cases of osteomyelitis that are culture positive for methicillin-resistant Staphylococcus aureus (MRSA), a vancomycin-eluting scaffold should be used [6,47]. If the organism is unknown or the treatment is prophylactic, one may instead opt for a broader-spectrum drug such as tobramycin which is effective against both gram-positive and gram-negative bacteria [48].…”

Antibacterial Composite Materials Based on the Combination of Polyhydroxyalkanoates With Selenium and Strontium Co-substituted Hydroxyapatite for Bone Regeneration

“…Antibacterial ion release studies were performed on composite films against S. aureus 6538P or E. coli 8739, following an adapted method described by Cao et al (2017) . Samples of 6 mm in diameter were incubated in 1 mL of Mueller Hinton broth at 37°C for 1, 3, 6, and 24 h. After each time point, the media with the eluted ions were collected and replaced with fresh media.…”

Vancomycin Loaded Alginate/Cockle Shell Powder Nanobiocomposite Bone Scaffold for Antibacterial and Drug Release Evaluation

“…(1) DRUG RELEASE STUDY Drug release study was conducted based on modified methods of Cao et al (2017) and Zhang et al (2012). Scaffolds were immersed in 10 mL of simulated body fluid (SBF) and incubated at 37 °C.…”