Joonas Mikkonen

University of Tampere, Tampere, Western Finland, Finland

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Publications (16)38 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: To investigate in vitro whether pH ranging between 6 and 9 has an effect on the degradation of stent fibers made of poly(l-lactide-co-glycolide) (PLGA) 80/20. The fibers were divided into three groups and immersed in sodium phosphate-buffered saline (Na-PBS) solution with three different pH values: 6, 7.4, and 9. The mechanical and thermal properties were studied, and scanning electron microscopy (SEM) images were taken at specific time points of hydrolysis. The tensile testing showed that the strength of the fibers decreased through hydrolysis and was lost at 8 weeks in all groups. The T(m) and T(g) of the PLGA fibers did not indicate any significant differences between the different groups. In SEM images taken at 4 weeks, there were no significant differences between the fibers immersed in Na-PBS solutions of different pH values. However, at 8 weeks the surface of the fiber immersed in saline with a pH of 6 seemed coarser than that of those immersed in neutral (pH 7.4) or alkaline (pH 9) Na-PBS. The studied pH values did not influence the degradation behavior of the PLGA 80/20 fibers. Therefore, rabbits can be used as model animals for human biodegradable urological devices even though the pH of their urine is different.
    Journal of endourology / Endourological Society 12/2011; 26(6):701-5. · 1.75 Impact Factor
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    ABSTRACT: To evaluate the effect of an indomethacin-eluting biodegradable urethral stent on the production of inflammatory cytokines in vitro and the degradation and biocompatibility of the new stent in vivo. The effects of an indomethacin and indomethacin-eluting biodegradable stent on monocyte chemoattractant protein (MCP)-1, RANTES (regulated on activation, normal T-cell expressed and secreted), and transforming growth factor-ß were measured in THP-1 cells by enzyme-linked immunosorbent assay. Stents (copolymer of L-lactide and glycolide acid) that were coated with 50L/50D polylactic acid and two different concentrations of indomethacin were inserted into the rabbit urethra. Stents without the drug were used as controls. Scanning electron microscopy (SEM) was used to assess the degradation of the stents. Biocompatibility was evaluated using histologic analyses of the urethral specimen. The measurements were performed at 3 weeks and 3 months. Indomethacin and indomethacin-releasing stent material inhibited MCP-1 and RANTES production in activated THP-1 macrophages. SEM analysis revealed that indomethacin coating had no effect on the degradation process of the stents and less epithelial polyposis had developed in the indomethacin stent group. In histologic analyses at 3 weeks, indomethacin-eluting stents caused more calcification but no significant differences in other tissue reactions. At 3 months, the indomethacin-eluting stents caused less inflammatory reaction and calcification compared with the control stents. Indomethacin-eluting property can be safely added to biodegradable stents without major influence on the degradation time. The development of epithelial polyposis in the urethra can be potentially reduced by the new indomethacin-eluting urethral stents.
    Journal of endourology / Endourological Society 11/2011; 26(4):387-92. · 1.75 Impact Factor
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    ABSTRACT: To investigate the effects of biodegradable stent material (poly-96L/4D-lactic acid [PLA]) on the production of cytokines and other inflammatory mediators in vitro and the biocompatibility of new drug-eluting biodegradable urethral stent materials in vivo. Indomethacin, dexamethasone, and simvastatin were used in the materials. The effects of the biodegradable stent material on cytokines and other inflammatory mediators were measured using the Human Cytokine Antibody Array and enzyme-linked immunosorbent assay in THP-1 cells, with bacterial lipopolysaccharide as a positive control. To assess the biocompatibility of the stent materials, we used muscle implantation. Biodegradable stent materials without drug-eluting properties and silicone and latex were used as controls. The measurements were done at 3 weeks and 3 months. The PLA stent material induced production of inflammatory mediators, especially interleukin-8, tumor necrosis factor-alpha, and transforming growth factor-beta, in vitro. The increase in the production of these mediators with the PLA stent material was smaller than in the cells treated with lipopolysaccharide. In vivo, the effects of the biodegradable materials did not differ at 3 weeks, although, at 3 months, dexamethasone had induced more tissue reactions than had the other materials. At 3 months, fibrosis and chronic inflammatory changes were decreased in the biodegradable material groups compared with the positive control. PLA stent material increased the production of cytokines and other inflammatory mediators less than did positive controls in vitro. The in vivo biocompatibility of the drug-eluting biodegradable materials was better than that of the positive controls. Drug-eluting biodegradable urethral stents could potentially offer a new treatment modality in the future.
    Urology 08/2009; 75(1):229-34. · 2.42 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the drug elution properties of novel drug-eluting bioabsorbable stents in vitro with four different drugs: dexamethasone, indomethacin, simvastatin and ciprofloxacin. Braided stents of poly-lactic acid (96l/4d) fibers were coated with a solution containing the appropriate bioabsorbable polymer and drug, with acetone as the solvent. Two different drug concentrations for both non-sterile and gamma sterilized stents were used for dexamethasone and indomethacin. For ciprofloxacin and simvastatin, only one drug dose was used. The stents were placed in sodium-phosphate-buffered saline in a shaking incubator (pH 7.4, +37 degrees C) and the eluted drug was measured periodically using an ultraviolet spectrometer. The drugs were hydrophobic to different degrees, as demonstrated by their various speeds of elution. In general, the higher the drug load in the stent, the faster the drug elution and the more hydrophilic the elution profile. In the cases of dexamethasone, indomethacin and ciprofloxacin, the sterilization decreased the drug elution rate slightly and the elution started earlier. However, in the case of ciprofloxacin, the gamma sterilization increased the drug elution rate slightly. Sustained elution was achieved for all four drugs. It was also evident that both the concentration and the hydrophility of the drug had a great influence on the drug elution profile. Gamma sterilization modified the drug elution profiles of dexamethasone, indomethacin and simvastatin, but had little effect on the drug elution profile of ciprofloxacin compared to three other drugs.
    Acta biomaterialia 05/2009; 5(8):2894-900. · 5.09 Impact Factor
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    ABSTRACT: To assess the effect of drug-eluting properties on the degradation process and the biocompatibility of biodegradable drug-eluting urethral stents. Braided biodegradable 80 L/20D-PLGA (copolymer of polylactide and polyglycolide) stents with drug-eluting properties were used as the test material. The drugs analysed were indomethacin, dexamethasone and ciprofloxacine. 80 L/20D-PLGA stents without a drug coating served as controls. In all, 16 male rabbits were used and divided into four groups. The stents were inserted under general anaesthesia into the posterior urethra. After 1 month, the rabbits were killed and the urethra removed for histological and optic microscopy analyses. Control stents and the dexamethasone-eluting stents degraded totally during the follow-up period. Conversely, in both indomethacin- and ciprofloxacine-eluting stent groups, the degradation process was significantly delayed and they induced an increase in epithelial hyperplasia. Histological analysis showed that all the stents induced eosinophilia, but there were no significant differences in the intensity of acute or chronic inflammatory reactions and fibrosis. A drug-eluting capacity can be added to biodegradable stents. The addition of a drug influences the biodegradation time of PLGA urethral stents. Further studies are needed, to find the proper concentrations and releasing profiles of the drugs to achieve the desired bioactivity and biocompatibility properties.
    BJU International 12/2008; 103(8):1132-5. · 3.05 Impact Factor
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    ABSTRACT: To evaluate, in a pilot study, the efficacy and safety of combining a braided poly(lactic-co-glycolic acid) (PLGA, a copolymer of l-lactide and glycolide) urethral stent and dutasteride in the treatment of acute urinary retention (AUR) due to benign prostatic enlargement (BPE). Ten men with AUR due to BPE were treated as outpatients. A biodegradable braided PLGA urethral stent was inserted into the prostatic urethra, using a specially designed insertion device under visual control. Dutasteride treatment was started and the patients were followed up for 3 months after insertion of the stents. In all patients the stents were placed successfully with the new insertion device. All men were able to void after inserting the stent. At 1 month five patients voided freely with a low residual urine volume (<150 mL), two voided but had a high residual urine volume and a suprapubic catheter was placed, and three needed a suprapubic or an indwelling catheter before 1 month, due to AUR or comorbidities. At 3 months five patients were voiding with no problems. We have developed a new and effective insertion device for biodegradable braided prostatic stents. The new braided-pattern stent overcomes the earlier problems of migration and sudden breakage into large particles associated with biodegradable spiral stents. However, the mechanical properties of the new stent need to be improved and tested in a longer follow-up. We consider that this new biodegradable braided-pattern urethral stent could provide a new option in the future treatment of AUR.
    BJU International 11/2008; 103(5):626-9. · 3.05 Impact Factor
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    ABSTRACT: Endoscopic stenting is one treatment method for pancreatic strictures or pseudocysts in patients with symptomatic chronic pancreatitis. With a biodegradable stent, the later removal of the stent could be avoided. We investigated the degradation, patency, and toxicity of a novel biodegradable, self-expanding radiopaque polylactide-barium sulfate pancreatic stent in a large animal model. Animal study. Five swine had a biodegradable pancreatic stent placed into the pancreatic duct (PD) and were followed-up for 6 months. Repeated blood tests and radiographs were studied during the follow-up. The animals were euthanized at 6 months, at which time, the PD inner diameter was measured, and histology was analyzed and graded. For comparison, histology from 5 nonstented animals was also analyzed. The stent was correctly inserted into the PD in 4 of 5 animals. All the animals remained healthy, gained weight, and showed no signs of pancreatitis. A radiograph showed that the stent was in its original place in all animals at 1 month but had disappeared in all animals by 3 months. At 6 months, the autopsied pancreatic tissue was soft, and the PD was patent in all of the animals. The PD was slightly dilated at the site of the stent in the head of the pancreas compared with the preoperative diameter (5 mm [range 3-6 mm] vs 2 mm [range 1-3 mm], P < .05), but, in the body of the pancreas, no significant dilatation was seen. In the histology of the pancreata, there was no difference between the samples from the exposed parts of the biodegradable pancreatic stent compared with the distal nonexposed parts, or to the samples from the nonstented animals. This novel biodegradable pancreatic stent, studied in these swine, appeared to be safe for use in the PD. These encouraging results warrant further clinical trials with this biodegradable pancreatic stent in pancreatic applications in human beings.
    Gastrointestinal endoscopy 06/2008; 67(7):1106-12. · 6.71 Impact Factor
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    ABSTRACT: The biodegradable PLGA (a copolymer of L-lactide and glycolide) urethral stent with a spiral configuration has been used clinically for the prevention of postoperative urinary retention after different types of thermal therapy for benign prostatic hyperplasia. A new braiding pattern for this stent has recently been developed by our group. The aim here was to investigate the in situ degradation and biocompatibility of the new braided stent in the rabbit urethra. PLGA stents with a one-over-one braiding pattern and steel stents served as controls that were inserted into the posterior urethras of 24 male rabbits using a special delivery instrument. The animals were sacrificed after 1 week, 1 month, 2 months, or 4 months, and light microscopy and histologic analyses were performed. The delivery instrument worked well and cystoscopy was not needed in the insertion process. The braided PLGA stents degraded smoothly in 1 to 2 months. The metallic stents induced more epithelial hyperplasia and epithelial changes than the biodegradable stents at all time points analyzed. These differences increased during follow-up. The degradation process was well controlled and the biodegradable stents were more biocompatible than the metallic stents. The new stent can be inserted into the posterior urethra without cystoscopic aid.
    Journal of Endourology 05/2008; 22(5):1065-9. · 2.07 Impact Factor
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    ABSTRACT: Drug-eluting stents are a recent innovation for endovascular and endourethral purposes. The aim of this study was to assess the biocompatibility of new biodegradable drug-eluting stent materials in vivo. Rods made of SR-PLDLA (self-reinforced poly-96L,4D: -lactic acid) covered with P(50L/50D)LA and rods made of 96L/4D SR-PLA and covered with P(50L/50D)LA including indomethacin 3.3 microg/mm(2)or dexamethasone 1.5 microg/mm(2), were inserted into the dorsal muscles of 20 rabbits serving as test animals. Rods made of silicone and organotin-positive polyvinylchloride were used as negative and positive controls. The animals were sacrificed after 1 week, 1 month, 2 months or 4 months. Histological changes attributable to the operative trauma were seen in all specimens at 1 week and 1 month. At 2 months both dexamethasone and indomethacin induced less fibrosis than the plain SR-PLDLA covered with P(50L/50D)LA without drug. At 4 months dexamethasone induced both chronic inflammatory changes and foreign body reaction, whereas the reactions in the indomethacin and drug-free plain SR-PLDLA groups were insignificant. The new biodegradable drug-eluting stent materials are highly biocompatible. Drug-eluting biodegradable stents may offer a promising new treatment modality for vascular and urethral diseases. However, further studies are needed to demonstrate their feasibility and efficacy.
    Journal of Materials Science Materials in Medicine 09/2007; 18(8):1543-7. · 2.14 Impact Factor
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    ABSTRACT: A bile leak is a common complication after a cholecystectomy. The use of a novel, self-expanding, radiopaque polylactide-barium sulphate biodegradable stent and a polyethylene stent was investigated in 12 pigs with cystic-duct leakage. Prospective animal study. After cholecystectomy, the cystic duct was left without ligation, and then the foramen of Winslow was drained extra-abdominally. During the duodenoscopy, a biodegradable or a polyethylene biliary stent was inserted into the bile duct. The bile-drain output was measured daily, and when it was below 20 mL/d, the drain was removed. The animals were followed by repeated abdominal radiographs and serum determinations until they were euthanized at 6 months, when histologic evaluation of the bile duct and surrounding tissues was performed. In the biodegradable stent group, the total external output of bile was significantly smaller (median [range], 165 mL [100-1740 mL] vs 710 mL [355-1020 mL]; P<.01) and the drains could be removed earlier (5 days [4-5 days] vs 7 days [6-7 days] after surgery; P<.05) compared with the plastic stent group. In the abdominal radiograph, a biodegradable or polyethylene stent was seen to be in place in all animals at 3 months and in 0 of 6 (biodegradable biliary stent group) and 1 of 5 (polyethylene biliary stent group) animals at 6 months. One polyethylene stent was found to be clotted at the necropsy at 6 months. The rest of the stents had disappeared by 6 months, and there was no significant difference in the bile-duct inner diameter or the histology between the groups. This novel biodegradable stent is applicable, safe, and effective in the endoscopic treatment of postcholecystectomy cystic-duct leakage. In addition, the subsequent removal of the stent can be avoided. These encouraging experimental results warrant further clinical trials.
    Gastrointestinal Endoscopy 06/2007; 65(7):1063-8. · 5.21 Impact Factor
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    ABSTRACT: During recent years, we have been developing bioabsorbable biliary stents with promising experimental results. In developing pancreatic stents before long-term experiments, the acute toxicity to the pancreas of a bioabsorbable, radiopaque polylactide (PLA 96-barium sulfate, BaSO4) stent material was investigated. The pancreas of 65 Sprague-Dawley rats was exposed either to radiopaque stent material [PLA 96 with 25% (w/w) of BaSO4], radiolucent stent material (PLA 96), or inert steel by inserting a 5-mm-long (diameter 0.3 mm) fiber/stick of material into the pancreas after laparotomy under general anesthesia. Pancreatic tissue specimens and blood samples were taken after 1, 3, 7, and 21 days for histological examination and amylase activity measurements. Samples were also taken from 5 baseline (control) rats without exposing to any materials. The baseline serum amylase activity was normal, and no histological changes in the pancreas were observed. A significant increase (mean +/- SE) in the serum amylase activity was observed only on day 1 in the animals having radiopaque stent material (PLA 96-BaSO4; 5,845 +/- 1,135 U/l), steel (4,946 +/- 667 U/l), or radiolucent stent material (PLA 96; 7,684 +/- 667 U/l) inserted. There was slightly more acinar cell necrosis on day 7 in the steel group than in the radiopaque stent (PLA 96-BaSO(4)) group (p = 0.028). Radiopaque stent material (PLA 96-BaSO4) was not more toxic than the reference steel material in the rat pancreas during the 21-day observation period and is thus applicable for further in vivo experiments when developing pancreatic bioabsorbable stents.
    Pancreatology 02/2006; 6(4):301-5. · 2.04 Impact Factor
  • European Urology Supplements - EUR UROL SUPPL. 01/2006; 5(2):284-284.
  • European Urology Supplements - EUR UROL SUPPL. 01/2006; 5(2):60-60.
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    ABSTRACT: To evaluate in vivo a new drug-eluting biodegradable vascular stent with respect to biocompatibility, neointimal hyperplasia formation, and reliability. Self-expanding biodegradable poly-96L/4D-lactic acid (PLA) stents with 2 drugs (PLA + dexamethasone [DEX] and PLA + simvastatin [SIM]) and 2 different coatings (PLA + P(D,L)LA and PLA + polycaprolactone [PCL]) were compared with a self-expanding stainless steel Wallstent. The stents were implanted in both common iliac arteries of 8 pigs. Prior to sacrifice at 1 month, angiography was performed to determine patency. Specimens were harvested for quantitative histomorphometry; vascular injury and inflammation scores were assigned to the stented iliac segments. All stented arteries were angiographically patent. The mean luminal diameter (3.05 mm) and area (30.36 mm2) of DEX-eluting PLA stents were decreased compared to other stents (PLA + P(D,L)LA: 3.66 mm and 43.92 mm2; PLA + SIM: 4.21 mm and 56.48 mm2; PLA + PCL: 4.19 mm and 54.64 mm2; Wallstent: 5.01 mm and 81.19 mm2). Wallstents and DEX-eluting PLA stents induced minimal intimal hyperplasia: PLA + DEX: 0.16 mm, PLA + P(D,L)LA: 0.35 mm, PLA + SIM: 0.33 mm, PLA + PCL: 0.29 mm, and Wallstent: 0.18 mm. The vascular injury scores demonstrated only mild vascular trauma for all stents. Only mild to moderate inflammatory reaction was noted around stent struts with a vascular inflammation score. Biodegradable polymer stents appear to be biocompatible and reliable, causing minimal neointimal hyperplasia. Furthermore, the new biodegradable poly-D/L-lactic acid stent can be used as a local drug delivery vehicle. The DEX-eluting PLA stent reduces neointimal hyperplasia. The findings show a need for further investigation to prove the efficacy and safety of this new biodegradable drug-eluting stent.
    Journal of Endovascular Therapy 07/2005; 12(3):371-9. · 2.70 Impact Factor
  • Gastrointestinal Endoscopy - GASTROINTEST ENDOSCOP. 01/2005; 61(5).
  • European Urology Supplements - EUR UROL SUPPL. 01/2005; 4(3):243-243.