ABSTRACT
Avascularity and hypoxia result in avascular necrosis and play a negative role in fracture healing. The FDA-approved iron chelating agent, desferoxamine (DFO) in a liquid form, has been shown to induce angiogenesis and improve fracture healing through upregulation of the vascular endothelial growth factor. We were concerned that local injection of DFO would either fail to adequately deliver sufficient drug to the desired site or lead to undesired delivery to adjacent sites. Therefore, a sustained release delivery system was desirable to direct DFO to the intended site. Calcium sulfate pellets, collagen sponges, and demineralized cortical bone matrix were all evaluated as potentially controlled release systems for DFO using a fetal mouse metatarsal angiogenesis assay. Angiogenesis was analyzed using a vascularity grading scale, by measuring the mean vessel length of the 5 longest vessels, and by counting the mean number of vessels per metatarsal. Although there was some evidence of angiogenesis with all three carriers, DFO loaded CaSO4 pellets increased vascularity grading, the mean length of the five longest vessels, and the mean number of vessels, all by statistically significant margins versus the control. These results suggest that CaSO4 pellets could be used as a viable, nontoxic, controlled release system for DFO in clinical situations where increased angiogenesis and bone growth are desirable.
Subject(s)
Deferoxamine/administration & dosage , Drug Carriers/chemistry , Vascular Endothelial Growth Factor A/biosynthesis , Animals , Biocompatible Materials/chemistry , Bone Matrix/chemistry , Calcium Sulfate/chemistry , Collagen/chemistry , Drug Delivery Systems , Female , Fracture Healing/drug effects , Humans , Hypoxia-Inducible Factor 1/metabolism , Materials Testing , Mice , Mice, Inbred C57BL , Neovascularization, Physiologic/drug effects , Osteonecrosis/drug therapy , Osteonecrosis/therapy , Pregnancy , Up-Regulation/drug effectsABSTRACT
OBJECTIVE: Bacterial infection of the pin tract represents the most common complication associated with external fixation. This study was designed to evaluate the antibacterial activity of nitric oxide (NO)-releasing xerogel films applied to commercially pure titanium pins in a rat model. METHODS: Pins were coated with xerogel solution through a dip-coating procedure. Half of the xerogel-coated implant pins were modified into NO donors and served as the NO-releasing group, whereas the remaining pins were left unmodified to serve as non-NO-releasing xerogel-coated controls. Acid-etched pins served as uncoated controls. Animal selection was randomized and every rat had one pin from each of the three groups randomly allocated to the third, fourth, or fifth tail vertebrae. Quantification of bacterial infection was performed 48 days postoperatively and the tissue-implant interface was inspected for clinical signs of infection on Days 14 and 28 postimplantation. RESULTS: Pin tract bacterial colony counts of the NO-releasing group (170,000 ± 181,000) were significantly lower than both the xerogel-coated group (677,000 ± 675,000) and the control group (1,181,000 ± 2,717,000) 48 days postoperatively (P < 0.05). No significant difference in colony counts was observed between the xerogel-coated group and the control group. The NO-releasing group also had significantly fewer clinical signs of infection than both the coated and the control groups on postoperative Day 28 (P < 0.05). CONCLUSION: The application of NO-releasing xerogel coatings can inhibit bacterial colonization of external fixation pins both during the initial postsurgical period and up to 48 days postimplantation.
