The effect of pH on the degradation of biodegradable poly(L-lactide-co-glycolide) 80/20 urethral stent material in vitro.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Biodegradable braided poly(lactic-co-glycolic acid) urethral stent combined with dutasteride in the treatment of acute urinary retention due to benign prostatic enlargement: a pilot study.

OBJECTIVE: 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). PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A new biodegradable braided self-expandable PLGA prostatic stent: an experimental study in the rabbit.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

A novel biodegradable biliary stent in the normal duct hepaticojejunal anastomosis: an 18-month follow-up in a large animal model.

Creating a well-functioning hepaticojejunostomy (HJ) anastomosis with nondilated bile ducts remains a challenge. Our aim was to study the use in a large animal model of a novel, braided polylactide barium sulfate biodegradable biliary stent (BDBS) without external connection and with no need for later removal. Fifty swine were randomly operated on for Roux-Y HJ with or without BDBS in the anastomosis, and followed up (dynamic biligraphy, x-ray, serum determinations, anastomosis inner diameter, and histology) for 1.5, 3, 6, 12, and 18 months. During the follow-up, one nonstented animal died because of anastomotic leakage. In x-ray BDBS was seen in place until 1.5 months in all of the stented animals. In the nonstented animals HJ anastomosis inner diameter was decreased at 18 months [6.3 (5.0-7.0) mm vs 7.4 (7.0-9.0) mm, p = 0.05] and liver clearance reduced at 12 and 18 months compared to stented animals. Serum liver values and liver and bile duct histology did not differ between the groups. We conclude that this novel BDBS is easy to insert into the HJ anastomosis with nondilated ducts. It is nontoxic, dissolves safely, and may be associated with a larger and better draining anastomosis at 18-month follow-up. These results encourage us to proceed to clinical studies.

Tyrosine-derived polycarbonate membrane in treating mandibular bone defects. An experimental study.

This study was designed to evaluate the suitability of a novel bioabsorbable material in treating bone defects. A poly(desaminotyrosyl-tyrosine-ethyl ester carbonate) (PDTE carbonate) membrane (thickness 0.2-0.3 mm) was implanted into the mandibular angle of 20 New Zealand White rabbits to cover a through-and-through defect (12 x 6 mm). In group 1, the defects were left unfilled but covered with membrane and in group 2 the defects were filled with bioactive glass mesh and covered with membrane, too. Controls were left uncovered and unfilled. The animals were followed for 6, 12, 24 and 52 weeks, respectively. The material was evaluated by qualitative analysis of histological reactions and newly formed bone. We found that PDTE carbonate elicited a modest foreign body reaction in the tissues, which was uniform throughout the study. New bone formation was seen in all samples after six weeks. Group 1 had more new bone formation until 24 weeks and after this the difference settled. Based on findings of this study it was concluded that PDTE carbonate membranes have good biocompatibility and are sufficient to enhance bone growth without additional supportive matrix.

Platelet deposition on stainless steel, spiral, and braided polylactide stents. A comparative study.

Platelets play a key role in (sub)acute thrombotic occlusion after stenting. We examined the possible differences between biodegradable polylactide (PLA) and stainless steel (SS) stents in platelet attachment and morphology after whole blood perfusion. PLA stents of different configurations (spiral/braided) and polycaprolactone-polylactide (PCL-PLA)-coatings, or SS stents were implanted into a PVC tube (Ø 3.2 mm), with or without precoating of the tube with type-I collagen. PPACK (30 microM)-anticoagulated blood with (3)H-serotonin prelabeled platelets was perfused (flow rate: 30 ml/min, 90 s) over the stents. Platelet deposition was assessed by scintillation counting and morphology by scanning electron microscopy (SEM). To examine coagulation activation, plasma prothrombin fragments (F1 + 2) were measured before and after the perfusion. Protein deposition on PLA/SS stents was assessed at augmented shear forces mimicking coronary flow (rate: 60 ml/min, 60 s) under minimal anticoagulation (PPACK 1 microM). More platelets deposited on PLA stents than on SS stents under all study conditions (p < 0.03). Under anticoagulation (PPACK 30 microM) the generation of F1 + 2 remained unaltered. Under higher flow rate and limited anticoagulation SS stents accumulated 3.27 +/- 0.75 microg and PLA stents 5.25 +/- 1.74 microg of protein (Mean +/- SD, p <0.95). Among all biodegradable stents, the braided PLA stent coated with PCL-PLA-heparin accumulated the fewest platelets (p < 0.02). In SEM, signs of platelet activation on braided heparin-coated PLA stents, when compared with uncoated braided PLA/SS stents, appeared modest. In conclusion, PCL-PLAheparin coating of biodegradable stents may enhance their hemocompatibility, expressed by less platelet deposition. Nevertheless, materials, design, and coating techniques of biodegradable stents must be further developed.

Biodegradable self-expanding poly-L/D-lactic acid vascular stent: a pilot study in canine and porcine iliac arteries.

PURPOSE: To report results of an in vivo pilot study to evaluate the biocompatibility and delivery system of a new biodegradable vascular stent and validate the study design. METHODS: Two self-expanding intravascular stents, a biodegradable poly-D/L-lactic acid (PLA) and a medical stainless steel stent (Wallstent) were implanted in the common iliac arteries of 2 postpuberal female pigs and 3 laboratory-bred beagle dogs. Specimens were harvested after 45 days in the dogs and 32 days in the pigs for histomorphometry of the stented iliac artery segments. Preliminary measurements were made to assess the reliability of the quantitative histomorphometric measurements before final measurements. RESULTS: Histomorphometry analyses showed that mean luminal diameter and area were decreased in the PLA stent group (1.97+/-0.48 mm and 14+/-6.4 mm2, respectively) compared to the control stent group (4.28+/-0.83 mm and 61+/-19 mm2, respectively). The intimal thickness was higher in the PLA stent group (0.65+/-0.07 mm) than in the control group (0.44+/-0.21 mm). The mean injury score was 0.19+/-0.12 in the PLA stent group and 0.78+/-0.39 in the controls. In the PLA stent group, the mean inflammation score was 1.46+/-0.78 compared to 0.58+/-0.40 in the control group. There were no differences observed between the animal models. CONCLUSIONS: The PLA stent showed increased neointimal formation and reduced patency during early follow-up. Mechanical properties of the new biodegradable vascular stents are still inadequate, and the stent and the delivery device require modifications. The study methods were assessed as reliable and reproducible.

Requirements for quantitative analysis of intimal reaction in arteries treated with intraluminal stents.

PURPOSE: To assess the reliability of quantitative histomorphometry measurements for the intimal reaction that occurs after intraluminal stenting in an animal model. METHODS: Two self-expanding intravascular stents, a biodegradable poly-D/L-lactic acid (PLA) stent and a stainless steel Wallstent, were implanted in the common iliac arteries of a beagle dog. After 45 days, the histomorphometry of the stented iliac artery segments was quantitatively measured. The relative standard error (RSE) of the estimate was calculated, and the reliability of measurements for maximal (LDmax) and minimal (LDmin) luminal diameters and internal (IELT) and external (EELT) elastic lamina thicknesses was assessed. RESULTS: The PLA stent required more measurements of variables from a single slide to ensure reliable (RSE<10%) results (1 for LDmax, 1 for LDmin, 8 for IELT, and 4 for EELT) compared to the Wallstent (1 for LDmax, 1 for LDmin, 2 for IELT, and 2 for EELT 2). The measured results were reliable for both stent materials when variables were measured from 2 slides of each segment (proximal/central/distal) of the stent. CONCLUSIONS: We conclude that these preliminary measurements to estimate the reliability of quantitative histomorphometry measurements should be made and reported before final results are given.