Antibacterial poly(D,L-lactic acid) coating of medical implants using a biodegradable drug delivery technology.
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OBJECTIVES: Biomaterial-associated bacterial infections present common and challenging complications with medical implants. The purpose of this study was to determine the antibacterial properties of a low molecular weight biodegradable poly(D,L-lactic acid) coating with integrated antibiotics gentamicin and teicoplanin. METHODS: Coating of Kirschner-wires was carried out by a solvent casting technique under aseptic conditions with and without incorporated antibiotics. Release kinetics of gentamicin and teicoplanin were studied in phosphate-buffered saline. Initial bacterial adhesion of Staphylococcus epidermidis on coated and bare implants was determined by radiolabelling and counts of detached viable organisms. RESULTS: The incorporated antibiotics showed a continuous release over a period of at least 96 h with an initial peak of release in the first 6 h. Attachment of non-viable microorganisms, detected by radiolabelled bacteria, was increased significantly by the polymer coatings (P < 0.05). In contrast, the number of viable bacteria was reduced by the pure polymer (P < 0.01) and further by the polymer-antibiotic combinations (P < 0.05). CONCLUSIONS: Poly(D,L-lactic acid) coating of implants could offer new perspectives in preventing biomaterial-associated infections. Combinations with other drugs to formulate custom-tailored implant surfaces are feasible. (+info)
Biodegradable gelatin hydrogel potentiates the angiogenic effect of fibroblast growth factor 4 plasmid in rabbit hindlimb ischemia.
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OBJECTIVES: We investigated the potentiation of gene therapy using fibroblast growth factor 4 (FGF4)-gene by combining plasmid deoxyribonucleic acid (DNA) with biodegradable gelatin hydrogel (GHG). BACKGROUND: Virus vectors transfer genes efficiently but are biohazardous, whereas naked DNA is safer but less efficient. Deoxyribonucleic acid charges negatively; GHG has a positively charged structure and is biodegradable and implantable; FGF4 has an angiogenic ability. METHODS: The GHG-DNA complex was injected into the hindlimb muscle (63 mice and 55 rabbits). Gene degradation was evaluated by using (125)I-labeled GHG-DNA complex in mice. Transfection efficiency was evaluated with reverse-transcription nested polymerase chain reaction and X-Gal histostaining. The therapeutic effects of GHG-FGF4-gene complex (GHG-FGF4) were evaluated in rabbits with hindlimb ischemia. RESULTS: Gelatin hydrogel maintained plasmid in its structure, extending gene degradation temporally until 28 days after intramuscular delivery, and improving transfection efficiency. Four weeks after gene transfer, hindlimb muscle necrosis was ameliorated more markedly in the GHG-FGF4 group than in the naked FGF4-gene and GHG-beta-galactosidase (control) groups (p < 0.05, Kruskal-Wallis test). Synchrotron radiation microangiography (spatial resolution, 20 microm) and flow determination with microspheres confirmed significant vascular responsiveness to adenosine administration in the GHG-FGF4 group, but not in the naked FGF4-gene and the control. CONCLUSIONS: The GHG-FGF4 complex promoted angiogenesis and blood flow regulation of the newly developed vessels possibly by extending gene degradation and improving transfection efficiency without the biohazard associated with viral vectors. (+info)
Dose escalation of carmustine in surgically implanted polymers in patients with recurrent malignant glioma: a New Approaches to Brain Tumor Therapy CNS Consortium trial.
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PURPOSE: This New Approaches to Brain Tumor Therapy CNS Consortium study sought to determine the maximum-tolerated dose (MTD) of carmustine (BCNU) that can be implanted in biodegradable polymers following resection of recurrent high-grade gliomas and the systemic BCNU exposure with increasing doses of interstitial BCNU. PATIENTS AND METHODS: Forty-four adults underwent tumor debulking and polymer placement. Six patients per dose level were studied using polymers with 6.5%, 10%, 14.5%, 20%, and 28% BCNU by weight. Toxicities were assessed 1 month after implantation by a safety monitoring committee to determine whether subsequent escalations should occur. Nine additional patients were studied at the MTD to confirm safety. BCNU blood levels were obtained before and after polymer implantation. RESULTS: No dose-limiting toxicities were identified at the 6.5%, 10%, or 14.5% dose levels, although difficulties with wound healing, seizures, and brain edema were noted. At the 20% dose, these effects seemed more prominent, and six additional patients were treated at this dose and tolerated treatment well. Three of four patients receiving the 28% polymers developed severe brain edema and seizures, and accrual to this cohort was stopped. Nine additional patients received 20% polymer, confirming this as the MTD. Maximum BCNU plasma concentrations with the 20% loaded polymers were 27 ng/mL. Overall median survival was 251 days. CONCLUSION: The MTD of BCNU delivered in polymer to the surgical cavity is 20%. This polymer provides five times more BCNU than standard commercially available BCNU polymers and results in minimal systemic BCNU exposure. Additional studies are needed to establish the efficacy of high-dose BCNU polymers. (+info)
Biocorrosion of magnesium alloys: a new principle in cardiovascular implant technology?
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OBJECTIVES: To develop and test a new concept of the degradation kinetics of newly developed coronary stents consisting of magnesium alloys. METHODS: Design of a coronary stent prototype consisting of the non-commercial magnesium based alloy AE21 (containing 2% aluminium and 1% rare earths) with an expected 50% loss of mass within six months. Eleven domestic pigs underwent coronary implantation of 20 stents (overstretch injury). RESULTS: No stent caused major problems during implantation or showed signs of initial breakage in the histological evaluation. There were no thromboembolic events. Quantitative angiography at follow up showed a significant (p < 0.01) 40% loss of perfused lumen diameter between days 10 and 35, corresponding to neointima formation seen on histological analysis, and a 25% re-enlargement (p < 0.05) between days 35 and 56 caused by vascular remodelling (based on intravascular ultrasound) resulting from the loss of mechanical integrity of the stent. Inflammation (p < 0.001) and neointimal plaque area (p < 0.05) depended significantly on injury score. Planimetric degradation correlated with time (r = 0.67, p < 0.01). CONCLUSION: Vascular implants consisting of magnesium alloy degradable by biocorrosion seem to be a realistic alternative to permanent implants. (+info)
Matrix and bioabsorbable polymeric coils accelerate healing of intracranial aneurysms: long-term experimental study.
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BACKGROUND AND PURPOSE: Acceleration of intra-aneurysmal clot organization and fibrosis may be a solution to preventing aneurysm recanalization after endovascular treatment. The purpose of this study was to evaluate the short-term efficacy and long-term safety of the new Matrix coil system. METHODS: Matrix coils consist of thin platinum coils covered with a bioabsorbable, polymeric material (polyglycolic acid/lactide). Fifty-two experimental aneurysms were created in 26 swine. All of the aneurysms were tightly packed with Matrix or Guglielmi detachable coils (GDC). Comparative angiographic and histopathologic data were analyzed at 2 weeks (n=14), 3 months (n=6), and 6 months (n=6) after embolization. RESULTS: Three aneurysms treated with GDC ruptured despite tight packing. No recanalization or rupturing was observed in the aneurysms embolized with Matrix coils. At 14 days after embolization, the aneurysms treated with Matrix coils exhibited a more extensive area of organized thrombus when compared with the aneurysms treated with GDC (87% versus 75%, P=0.008, n=11). At 3 months, both Matrix and GDC-treated aneurysms demonstrated complete clot organization. Neck tissue thickness was higher in Matrix-treated aneurysms at 14 days and 3 months, but not at 6 months. No untoward parent artery stenosis was observed in aneurysms treated with Matrix during follow-up. The angiographic cross-sectional area of the Matrix-treated aneurysms was smaller than those treated with GDC at the 3 months. CONCLUSIONS: Matrix accelerated aneurysm fibrosis and neointima formation without parent artery stenosis. The Matrix system might prevent aneurysmal recanalization after endovascular treatment of cerebral aneurysms. (+info)
First evidence that bone marrow cells contribute to the construction of tissue-engineered vascular autografts in vivo.
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BACKGROUND: Materials commonly used to repair complex cardiac defects lack growth potential and have other unwanted side effects. We designed and tested a bone marrow cell (BMC)-seeded biodegradable scaffold that avoids these problems. METHODS AND RESULTS: To demonstrate the contribution of the BMCs to histogenesis, we labeled them with green fluorescence, seeded them onto scaffolds, and implanted them in the inferior vena cava of dogs. The implanted grafts were analyzed immunohistochemically at 3 hours and subsequently at 2, 4, and 8 weeks after implantation using antibodies against endothelial cell lineage markers, endothelium, and smooth muscle cells. There was no stenosis or obstruction caused by the tissue-engineered vascular autografts (TEVAs) implanted into the dogs. Immunohistochemically, the seeded BMCs expressing endothelial cell lineage markers, such as CD34, CD31, Flk-1, and Tie-2, adhered to the scaffold. This was followed by proliferation and differentiation, resulting in expression of endothelial cells markers, such as CD146, factor VIII, and CD31, and smooth muscle cell markers, such as alpha-smooth muscle cell actin, SMemb, SM1, and SM2. Vascular endothelial growth factor and angiopoietin-1 were also produced by cells in TEVAs. CONCLUSIONS: These results provide direct evidence that the use of BMCs enables the establishment of TEVAs. These TEVAs are useful for cardiovascular surgery in humans and especially in children, who require biocompatible materials with growth potential, which might reduce the instance of complications caused by incompatible materials and lead to a reduced likelihood of further surgery. (+info)
Plug migration and cement mantle assessment in total hip replacement.
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We reviewed a series of consecutive total hip replacements with cemented femoral components. Modern cementing techniques were followed in all cases, but two different medullary plugs were used-one was polyethylene and the other bioabsorbable gelatin. Cement mantle quality and plug migration were assessed by three different observers (X, Y, and Z); their findings did not agree. This was particularly evident when the cement mantles were assessed. There was a better cement mantle grading and less distal migration with polyethylene plugs, although there was no significant statistical difference between the two groups. (+info)
Staged management of giant abdominal wall defects: acute and long-term results.
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INTRODUCTION: Shock resuscitation leads to visceral edema often precluding abdominal wall closure. We have developed a staged approach encompassing acute management through definitive abdominal wall reconstruction. The purpose of this report is to analyze our experience with this technique applied to the treatment of patients with open abdomen and giant abdominal wall defects. METHODS: Our management scheme for giant abdominal wall defects consists of 3 stages: stage I, absorbable mesh insertion for temporary closure (if edema quickly resolves within 3-5 days, the mesh is gradually pleated, allowing delayed fascial closure); stage II, absorbable mesh removal in patients without edema resolution (2-3 weeks after insertion to allow for granulation and fixation of viscera) and formation of the planned ventral hernia with either split thickness skin graft or full thickness skin closure over the viscera; and stage III, definitive reconstruction after 6-12 months (allowing for inflammation and dense adhesion resolution) by using the modified components separation technique. Consecutive patients from 1993 to 2001 at a single institution were evaluated. Outcomes were analyzed by management stage, with emphasis on wound related morbidity and mortality, and fistula and recurrent hernia rates. RESULTS: Two hundred seventy four patients (35 with sepsis, 239 with hemorrhagic shock) were managed. There were 212 males (77%), and mean age was 37 (range, 12-88). The average size of the defects was 20 x 30 cm. In the stage I group, 108 died (92% of all deaths) because of shock. The remaining 166 had temporary closure with polyglactin 910 woven absorbable mesh. As visceral edema resolved, bedside pleating of the absorbable mesh allowed delayed fascial closure in 37 patients (22%). In the stage II group, 9 died (8% of all deaths) from multiple organ failure associated with their underlying disease process, and 96% of the remaining 120 had split-thickness skin graft placed over the viscera. No wound related mortality occurred. There were a total of 14 fistulae (5% of total, 8% of survivors). In the stage III group, to date, 73 of the 120 have had definitive abdominal wall reconstruction using the modified components separation technique. There were no deaths. Mean follow-up was 24 months, (range 2-60). Recurrent hernias developed in 4 of these patients (5%). CONCLUSIONS: The staged management of patients with giant abdominal wall defects without the use of permanent mesh results in a safe and consistent approach for both initial and definitive management with low morbidity and no technique-related mortality. Absorbable mesh provides effective temporary abdominal wall defect coverage with a low fistula rate. Because of the low recurrent hernia rate and avoidance of permanent mesh, the components separation technique is the procedure of choice for definitive abdominal wall reconstruction. (+info)