Dave W. Chen

Sustainable release of vancomycin, gentamicin and lidocaine from novel electrospun sandwich-structured PLGA/collagen nanofibrous membranes.

This study investigated the in vitro release of vancomycin, gentamicin, and lidocaine from novel electrospun sandwich-structured polylactide-polyglycolide (PLGA)/collagen nanofibrous membranes. For the electrospinning of biodegradable membranes, PLGA/collagen and PLGA/vancomycin/gentamicin/lidocaine were separately dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). They were then electrospun into sandwich structured membranes, with PLGA/collagen for the surface layers and PLGA/drugs for the core layer. After electrospinning, an elution method and HPLC assay were employed to characterize the in vitro release rates of the pharmaceutics over a 30-day period. The experiment showed that biodegradable nanofibrous membranes released high concentrations of vancomycin and gentamicin (well above the minimum inhibition concentration) for 4 and 3 weeks, respectively, and lidocaine for 2 weeks. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity of vancomycin and gentamicin ranged from 30% to 100% and 37% to 100%, respectively. In addition, results indicated that the nanofibrous membranes were functionally active in responses in human fibroblasts. By adopting the electrospinning technique, we will be able to manufacture biodegradable biomimetic nanofibrous extracellular membranes for long-term drug delivery of various pharmaceuticals.

Novel biodegradable sandwich-structured nanofibrous drug-eluting membranes for repair of infected wounds: an in vitro and in vivo study

Background The purpose of this study was to develop novel sandwich-structured nanofibrous membranes to provide sustained-release delivery of vancomycin, gentamicin, and lidocaine for repair of infected wounds. Methods To prepare the biodegradable membranes, poly(D, L)-lactide-co-glycolide (PLGA), collagen, and various pharmaceuticals, including vancomycin, gentamicin, and lidocaine, were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into sandwich-structured membranes with PLGA/collagen as the surface layers and PLGA/drugs as the core. An elution method and a high-pressure liquid chromatography assay were used to characterize in vivo and in vitro drug release from the membranes. In addition, repair of infected wounds in rats was studied. Histological examination of epithelialization and granulation at the wound site was also performed. Results The biodegradable nanofibrous membranes released large amounts of vancomycin and gentamicin (well above the minimum inhibition concentration) and lidocaine in vivo for more than 3 weeks. A bacterial inhibition test was carried out to determine the relative activity of the antibiotics released. The bioactivity ranged from 40% to 100%. The nanofibrous membranes were functionally active in treating infected wounds, and were very effective as accelerators in early-stage wound healing. Conclusion Using the electrospinning technique, we will be able to manufacture biodegradable, biomimetic, nanofibrous, extracellular membranes for long-term delivery of various drugs.

In Vitro Activities of Daptomycin-, Vancomycin-, and Teicoplanin-Loaded Polymethylmethacrylate against Methicillin-Susceptible, Methicillin-Resistant, and Vancomycin-Intermediate Strains of Staphylococcus aureus

ABSTRACT The objective of this study was to evaluate the antibacterial effects of polymethylmethacrylate (PMMA) bone cements loaded with daptomycin, vancomycin, and teicoplanin against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-intermediate Staphylococcus aureus (VISA) strains. Standardized cement specimens made from 40 g PMMA loaded with 1 g (low-dose), 4 g (middle-dose) or 8 g (high-dose) antibiotics were tested for elution characteristics and antibacterial activities. The patterns of release of antibiotics from the cement specimens were evaluated using in vitro broth elution assay with high-performance liquid chromatography. The activities of broth elution fluid against different Staphylococcus aureus strains (MSSA, MRSA, and VISA) were then determined. The antibacterial activities of all the tested antibiotics were maintained after being mixed with PMMA. The cements loaded with higher dosages of antibiotics showed longer elution periods. Regardless of the antibiotic loading dose, the teicoplanin-loaded cements showed better elution efficacy and provided longer inhibitory periods against MSSA, MRSA, and VISA than cements loaded with the same dose of vancomycin or daptomycin. Regarding the choice of antibiotics for cement loading in the treatment of Staphylococcus aureus infection, teicoplanin was superior in terms of antibacterial effects.

Comparison of Clinical Outcome in Primary Total Hip Arthroplasty by Conventional Anterolateral Transgluteal or 2-Incision Approach

Studies comparing the minimally invasive surgery with 2-incision technique (MIS-2) technique with the conventional transgluteal technique are lacking in the literatures. We compared the clinical outcomes in a series of 166 hips, including 83 MIS-2 total hip arthroplsty (THA) (group I) and another 83 matched-pair series (group II) using conventional transgluteal approach. Demographic data, hospital course, radiographic data, and functional outcome (Western Ontario and McMaster University Osteoarthritis Index and Harris hip score [HHS]) were investigated. The 2 groups significantly differed in 3 and 6-month HHS with a higher HHS in MIS-2 group. But the MIS-2 group had longer operation time, increased blood loss, and more complications. The current study indicates that the benefit of MIS-2 technique was only short-term with quicker functional recovery and shorter duration use of nonsteroid antiinflammatory drugs postoperatively.

Continuous intra-articular infusion of bupivacaine for post-operative pain relief after total hip arthroplasty: A randomized, placebo-controlled, double-blind study

Background: Instillation of local anesthetics into a surgical site has been gaining popularity in post‐operative pain management.

Local Cancellous Bone Grafting for Osteonecrosis of the Femoral Head

Objective. This study reports a novel local bone graft technique for the treatment of osteonecrosis of femoral head (ONFH). Materials and methods. From 1998 to 2005, a procedure using local bone grafting was performed for the treatment of ONFH in 11 patients. The local bone grafts were obtained from the intertrochanteric region and then impacted into the necrotic lesion. A wire coil was inserted into the remaining space after the grafting. Results. At a mean follow-up of 61 months (range, 30 to 103 months), all 5 ARCO stage IIC hips survived but 3 of the 6 ARCO stage IIIA hips failed. The overall clinical success rate was 73%. Conclusions. This study demonstrates that local cancellous bone grafting combined with a space-filling device implanted into the ONFH is a promising procedure and the wire coil showed no interference to the remodeling of the femoral head after grafting.

Biodegradable drug-eluting nanofiber-enveloped implants for sustained release of high bactericidal concentrations of vancomycin and ceftazidime: in vitro and in vivo studies

We developed biodegradable drug-eluting nanofiber-enveloped implants that provided sustained release of vancomycin and ceftazidime. To prepare the biodegradable nanofibrous membranes, poly(D,L)-lactide-co-glycolide and the antibiotics were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into biodegradable drug-eluting membranes, which were then enveloped on the surface of stainless plates. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vivo and in vitro release rates of the antibiotics from the nanofiber-enveloped plates. The results showed that the biodegradable nanofiber-enveloped plates released high concentrations of vancomycin and ceftazidime (well above the minimum inhibitory concentration) for more than 3 and 8 weeks in vitro and in vivo, respectively. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity ranged from 25% to 100%. In addition, the serum creatinine level remained within the normal range, suggesting that the high vancomycin concentration did not affect renal function. By adopting the electrospinning technique, we will be able to manufacture biodegradable drug-eluting implants for the long-term drug delivery of different antibiotics.

Preclinical Experiments on the Release Behavior of Biodegradable Nanofibrous Multipharmaceutical Membranes in a Model of Four-Wall Intrabony Defect

ABSTRACT Guided tissue regeneration (GTR) therapy has been widely used to regenerate lost periodontium from periodontal disease. However, in terms of regenerative periodontal therapy, a multidrug-loaded biodegradable carrier can be even more promising in dealing with periodontal disease. In the current study, we fabricated biodegradable nanofibrous collagen membranes that were loaded with amoxicillin, metronidazole, and lidocaine by an electrospinning technique. The in vitro release behavior and the cytotoxicity of the membranes were investigated. A four-wall intrabony defect was created in rabbits for in vivo release analysis. The bioactivity of the released antibiotics was also examined. The experimental results showed that the drug-loaded collagen membranes could provide sustainable release of effective amoxicillin, metronidazole, and lidocaine for 28, 56, and 8 days, respectively, in vivo. Furthermore, the bioactivity of the released antibiotics remained high, with average bioactivities of 50.5% for amoxicillin against Staphylococcus aureus and 58.6% for metronidazole against Escherichia coli. The biodegradable nanofibrous multipharmaceutical membranes developed in this study may provide a promising solution for regenerative periodontal therapy.

Finite element analysis of different repair methods of Vancouver B1 periprosthetic fractures after total hip arthroplasty.

OBJECTIVE To use finite element analysis to study the stability of different fixation methods used to repair Vancouver type B1 periprosthetic fractures occurring after total hip arthroplasty (THA). METHODS An artificial femur was used as the basis for the solid model; U2 series femoral stem (United Orthopedic Corporation, Hsinchu, Taiwan) was used for modelling of the prosthesis; and the modelling of the cable plate, wires and screws was based on information given in the manufacturers catalogue (Zimmer, Warsaw, IN, USA). The analysis model was constructed using the ANSYS software, and all material settings were based on literature values. A six-orifice cable plate, unicortical screws (20mm long and 4.5mm in diameter) and bicortical screws (50mm long and 4.5mm in diameter) were constructed. Four analysis models were defined. The basic model had a plate and three cable wires above the fracture line and two bicortical screws below the fracture line. In the second model, two unicortical screws were added above the fracture line. In the third model, three wires were added below the fracture line. In the fourth model, both the proximal screws of the second model and the distal wires of the third model were added to the basic model. To ensure that the numerical values produced by analysis reached convergence, mesh convergence was tested. RESULTS Adding two proximal unicortical screws to the basic Ogden construct (plate, proximal wires and distal screws) lessened displacement of the fracture and decreased the von Mises stress on the repair. Adding three distal wires to the basic construct had no noticeable effect. CONCLUSION Better fixation power is achieved by using both proximal and distal screws (the locking-plate concept) in treating Vancouver type B1 periprosthetic fracture after THA.

Intra-Articular Bupivacaine Reduces Postoperative Pain and Meperidine Use After Total Hip Arthroplasty: A Randomized, Double-Blind Study

One hundred patients receiving unilateral total hip arthroplasty (THA) were randomized to receive an intra-articular injection of 300mg bupivacaine or normal saline after completion of surgery. Pain scores of the bupivacaine group were significantly lower than those of the control group the first 12hours postoperatively (all, P<0.001). A significantly lower dose of meperidine was used in the study group than in the control group the first 24hours postoperatively (median, 25 vs. 45mg, P<0.001). Nineteen patients in the study group required meperidine the first day after surgery, as compared to 45 patients in the control group. We conclude that intra-articular injection of bupivacaine after THA reduces pain and meperidine use in the first 12hours after surgery.