Project description:ObjectiveLocal antibiotic delivery systems with differing chemical and mechanical properties have been developed to assist in the management of osteomyelitis. We investigated the bone conductive and resorptive capabilities of a calcium phosphate-calcium sulfate (CaP/CaS) composite compared with commercially available polymethylmethacrylate (PMMA). In addition, we compared the in vivo preventative and treatment efficacies of both biomaterials in a proven osteomyelitis model.MethodsSixty-four, male Sprague-Dawley rats were inoculated with 10 μl of 1.5 x 108 CFU/ml of Staphylococcus aureus in a surgically drilled defect in the right proximal tibia. Infected animals were randomly allocated into prevention and treatment groups with 32 rats each. In the prevention group, the defect was filled with a plug containing either PMMA or CaP/CaS immediately after the inoculation. In the treatment group, the infected defects were irrigated, debrided, and filled with either a PMMA or CaP/CaS plug. Both CaP/CaS and PMMA were impregnated with 10% weight of vancomycin. Rats were sacrificed 6 weeks after cement insertion. Infection was detected by bacterial culture and histological analysis. Bone formation in the defect was assessed with micro-computed tomography and histology.ResultsNo bacteria were detected in any group. Both the prevention and treatment groups using CaP/CaS had significantly more bone volume fraction, bone area, and cartilage area than the PMMA groups.ConclusionsWhen loaded with 10% of vancomycin, CaP/CaS and PMMA have the same efficacy for treatment and prevention of osteomyelitis. CaP/CaS enhances bone defect healing through improved bone remodeling in our osteomyelitis rat model.
Project description:Bone graft substitute such as calcium sulfate are frequently used as carrier material for local antimicrobial therapy in orthopedic surgery. This study aimed to assess the systemic absorption and disposition of tobramycin in patients treated with a tobramycin-laden bone graft substitute (Osteoset® T).Nine blood samples were taken from 12 patients over 10 days after Osteoset® T surgical implantation. Tobramycin concentration was measured by fluorescence polarization. Population pharmacokinetic analysis was performed using NONMEM to assess the average value and variability (CV) of pharmacokinetic parameters. Bioavailability (F) was assessed by equating clearance (CL) with creatinine clearance (Cockcroft CLCr). Based on the final model, simulations with various doses and renal function levels were performed. (ClinicalTrials.gov number, NCT01938417).The patients were 52 +/- 20 years old, their mean body weight was 73 +/- 17 kg and their mean CLCr was 119 +/- 55 mL/min. Either 10 g or 20 g Osteoset® T with 4% tobramycin sulfate was implanted in various sites. Concentration profiles remained low and consistent with absorption rate-limited first-order release, while showing important variability. With CL equated to CLCr, mean absorption rate constant (ka) was 0.06 h-1, F was 63% or 32% (CV 74%) for 10 and 20 g Osteoset® T respectively, and volume of distribution (V) was 16.6 L (CV 89%). Simulations predicted sustained high, potentially toxic concentrations with 10 g, 30 g and 50 g Osteoset® T for CLCr values below 10, 20 and 30 mL/min, respectively.Osteoset® T does not raise toxicity concerns in subjects without significant renal failure. The risk/benefit ratio might turn unfavorable in case of severe renal failure, even after standard dose implantation.
Project description:Antibiotic-loaded bone cement (ALBC) has become an indispensable material in orthopedic surgery in recent decades, owing to the possibility of drugs delivery to the surgical site. It is applied for both infection prophylaxis (e.g., in primary joint arthroplasty) and infection treatment (e.g., in periprosthetic infection). However, the introduction of antibiotic to the polymer matrix diminishes the mechanical strength of the latter. Moreover, the majority of the loaded antibiotic remains embedded in polymer and does not participate in drug elution. Incorporation of the various additives to ALBC can help to overcome these issues. In this paper, four different natural micro/nanoscale materials (halloysite, nanocrystalline cellulose, micro- and nanofibrillated cellulose) were tested as additives to commercial Simplex P bone cement preloaded with vancomycin. The influence of all four materials on the polymerization process was comprehensively studied, including the investigation of the maximum temperature of polymerization, setting time, and monomer leaching. The introduction of the natural additives led to a considerable enhancement of drug elution and microhardness in the composite bone cements compared to ALBC. The best combination of the polymerization rate, monomer leaching, antibiotic release, and microhardness was observed for the sample containing nanofibrillated cellulose (NFC).
Project description:In Response To: Walker RH. Reply to: Tardive dyskinesia-like syndrome due to drugs that do not block dopamine receptors: rare or non-existent: literature review. Tremor Other Hyperkinet Mov. 2019; 9. doi: 10.7916/3rez-p096 Original Article: D'Abreu A, Friedman JH. Tardive dyskinesia-like syndrome due to drugs that do not block dopamine receptors: rare or non-existent: literature review. Tremor Other Hyperkinet Mov. 2018; 8. doi: 10.7916/D8FF58Z9.
Project description:The purpose of this study was to compare bone regeneration and space maintaining ability of three-dimensional (3D) printed bone grafts with conventional biphasic calcium phosphate (BCP). After mixing polycaprolactone (PCL), poly (lactic-co-glycolic acid) (PLGA), and β-tricalcium phosphate (β-TCP) in a 4:4:2 ratio, PCL/PLGA/β-TCP particulate bone grafts were fabricated using 3D printing technology. Fabricated particulate bone grafts were mixed with atelocollagen to produce collagen-based PCL/PLGA/β-TCP composite block bone grafts. After formation of calvarial defects 8 mm in diameter, PCL/PLGA/β-TCP composite block bone grafts and BCP were implanted into bone defects of 32 rats. Although PCL/PLGA/β-TCP composite block bone grafts were not superior in bone regeneration ability compared to BCP, the results showed relatively similar performance. Furthermore, PCL/PLGA/β-TCP composite block bone grafts showed better ability to maintain bone defects and to support barrier membranes than BCP. Therefore, within the limitations of this study, PCL/PLGA/β-TCP composite block bone grafts could be considered as an alternative to synthetic bone grafts available for clinical use.
Project description:Acetabular bone loss is not uncommon when performing revision total hip arthroplasty. This can create a challenge, especially on the acetabular side. In the present report, our patient presented with aseptic loosening of the acetabular component. The patient had a Paprosky IIIA acetabular defect that was reconstructed with stacked acetabular augments in addition to a highly porous acetabular cup. The remaining bone defects were addressed through the use of a calcium sulfate/hydroxyapatite bone graft substitute. We set out to describe how to reconstruct severe acetabular bone loss with a combination of acetabular augments in addition to an injectable bone graft substitute as a novel method to address a complex clinical scenario.
Project description:BackgroundManagement of large infected bone defects is a major clinical and socioeconomic problem. The induced membrane technique has been widely used as a solution. However, it has apparent disadvantages such as limited autologous bone graft supply and lack of continuous infection control. Meanwhile, calcium sulfate/calcium phosphate composites have efficacious osteogenesis and antibiotic delivery capacity. For the first time, we analyzed the efficiency of calcium sulfate/calcium phosphate composites as a bone graft expander in the induced membrane technique to treat large infected bone defects.MethodsWe retrospectively analyzed the clinical data of 12 patients with large infected bone defects of 6.1-17.2 cm treated with the induced membrane technique from November 2016 to July 2019. In the second reconstruction stage, the bone defect was filled with a mixture of the autogenous iliac bone and vancomycin-impregnated calcium sulfate/calcium phosphate composites at a ratio of 3:1. We assessed the bony union by Samantha X-ray score and recorded infection recurrence and complications. Paley scale and SF-36 score were used to evaluate the function of adjacent joint and quality of life pre and postoperatively. Pearson's correlation coefficients were calculated for union time and other clinical scores.ResultsThe mean follow-up was 69 weeks (ranging from 30 to 142) after the second stage of the operation. The mean Samantha X-ray score was 5.1 [3-6], preoperative and postoperative SF-36 scores showed that there were statistical differences in all the nine aspects, and the excellent rate of adjacent joint function was 75% (Paley). All cases were radiologically healed, and none of the 12 patients had infection recurrence or failure of fixation at the last follow-up. Two cases had delayed wound healing and were cured after dress changing. There was a significant correlation between union time and Samantha X-ray score (r =‒0.887; P=0.000), while there was no correlation between filling dose, size of the defect, and other outcomes.ConclusionsThis study provided evidence supporting calcium sulfate/calcium phosphate composites as an effective and safe bone graft expander in the induced membrane technique to treat large infected bone defect. This technique may help decrease the use of autologous bone graft and enhance the anti-infection effect of the induced membrane technique.