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.

Evaluation of sustained ciprofloxacin release of biodegradable electrospun gelatin/poly(glycerol sebacate) mat membranes for wound dressing applications

“…This can be explained with release of CIP over time, and its antibacterial action covers fibroblasts by creating a three‐dimensional complex, which prevents access to suitable nutrition from culture media to the cells. This effect reduces metabolic activity of cells by preventing the transportation of essential molecules to cells at all time points …”

Stem Cell-Friendly Scaffold Biomaterials: Applications for Bone Tissue Engineering and Regenerative Medicine

“…Furthermore, gelatin-calcium phosphate nanofibers, composed of β-TCP nanoparticles incorporated into electropunk gelatin nanofibers, improved proliferation and osteogenic differentiation of rat MSCs compared to pure calcium phosphate nanofibers (Kuttappan et al, 2016). Lastly, gelatin is also an ideal carrier for proteins and various growth factors (Krishnan et al, 2015;Anjana et al, 2016). For example, Gelatin/HA fibrous scaffold with platelet-rich plasma gel was able to induce the differentiation of MSCs into an osteogenic cell line (Anjana et al, 2016).…”

Application of Collagen Implants in Achilles Tendon Injuries

“…Some researchers have cross-linked the collagen fibers with other biomaterials to enhance their biomechanical properties [35,36]. Others have incorporated some compounds to biomaterials and loaded in scaffolds to immobilize growth factors and prolong their retention at the defect site [37,38].…”