title: Evaluation of antibacterial activity and cytocompatibility of ciprofloxacin loaded gelatin-hydroxyapatite scaffolds as a local drug delivery system for osteomyelitis treatment.
abstract: Surgical debridement of the dead bone and subsequent systemic antibiotic therapy is often ineffective in eliminating Staphylococcus aureus infections in osteomyelitic patients. The recurrence of S. aureus infection is mainly due to the intracellular growth of bacterial colonies within osteoblast cells that protect the organism from extracellular host defences and/or antibiotic therapy. In this study, porous gelatin-hydroxyapatite (HAP) scaffolds with various amounts of ciprofloxacin (1, 2, 5, and 10 wt%) were fabricated by freeze-drying technique and the release of the antibiotic was characterized, as was the efficacy of the released antibiotic against methicillin-sensitive and methicillin-resistant S. aureus. Furthermore, the impact of the released antibiotic on the viability and osteogenic differentiation of human adipose-derived mesenchymal stem cells (ADMSCs) cultured on the scaffolds were assessed. Finally, the efficacy of the released ciprofloxacin to enter the cells and abate intracellularly located S. aureus was evaluated. All the groups of CGHA scaffolds displayed sustained release of ciprofloxacin against S. aureus for 60 days above the minimum inhibitory concentration for the target species with zero-order kinetics and Korsmeyer-Peppas models. While comparing, the released antibiotic from CGHA5 scaffolds was found to be effective at reducing S. aureus through the study period, without detrimental effects on human ADMSC viability or osteogenic potential. When stem cells internalized with S. aureus were cultured onto the drug-loaded scaffolds, a significant reduction in the colony count of internalized bacteria was observed, resulting in the osteogenic differentiation capability of those cells. Our results clearly demonstrate that the ciprofloxacin incorporated gelatin-HAP scaffolds, which were cytocompatible and could target both intracellular and extracellular S. aureus, defining its potential to be used as local drug delivery system.
authors.affiliation: Amrita Center for Nanosciences and Molecular Medicine, Amrita Institute of Medical Science and Research Center Campus, Amrita Vishwa Vidyapeetham University , Cochin, Kerala, India .
authors.forename: Amit G
authors.initials: AG
authors.lastname: Krishnan
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Jayaram
authors.forename: Raja
authors.initials: R
authors.lastname: Biswas
authors.forename: Manitha
authors.initials: M
authors.lastname: Nair
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D002939:Ciprofloxacin / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D017886:Durapatite / Q000737:chemistry*; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D010019:Osteomyelitis / Q000188:drug therapy*; D017550:Spectroscopy, Fourier Transform Infrared; D054457:Tissue Scaffolds / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin; D005780:Gelatin; D017886:Durapatite