Taina Isotalo

BIOCOMPATIBILITY TESTING OF A NEW BIOABSORBABLE X-RAY POSITIVE SR-PLA 96/4 URETHRAL STENT

PURPOSE Recently a first X-ray-positive bioabsorbable urethral stent was developed by our group. The stent is made from self-reinforced poly-L,D-lactic acid (SR-PLA 96/4) blended with barium sulfate. The aim of this study was to evaluate the biocompatibility properties of the new stent materials. MATERIALS AND METHODS Rods made from pure SR-PLA 96/4 and SR-PLA 96/4 blended with barium sulfate were inserted into the dorsal muscles of a rabbit. Rods made from latex and silicone were used as positive and negative controls. To evaluate the long-term effect of BASO4 after the bioabsorption of the polymer, fast degrading SR-PGA (self-reinforced polyglycolic acid) and SR-PLA + BASO4 rods were used as controls. Urethral stents made from SR-PLA 96/4 and X-ray-positive SR-PLA 96/4 stents were inserted cystoscopically into the rabbit urethra. Metal stents were used as controls. The animals were sacrificed after 1 week, 1 month or 6 months. RESULTS In the muscle implantation samples acute tissue reactions due to operative trauma were seen in all specimens at 1 week. After 6 months chronic inflammatory changes and foreign body reaction were seen only in the positive controls. The stent worked well in the rabbit urethra, its biocompatibility was good and there was less encrustation than in the metal stents. CONCLUSIONS This first X-ray-positive bioabsorbable urethral stent showed no toxic tissue effects.

A BIOABSORBABLE SELF-EXPANDABLE, SELF-REINFORCED POLY-L-LACTIC ACID URETHRAL STENT FOR RECURRENT URETHRAL STRICTURES: A PRELIMINARY REPORT

PURPOSE We studied whether a new bioabsorbable self-expandable, self-retaining and self-reinforced poly-l-lactic acid double spiral stent is able to prevent the edges of a cut recurrent urethral stricture from adhering together and the scar from shrinking, thus obviating stricture recurrence. MATERIALS AND METHODS A bioabsorbable spiral stent was inserted into the stricture site in the urethra immediately after optical urethrotomy in 22 patients with recurrent urethral stricture. Uroflowmetry, measurement of residual urine volume, urine culture and urethroscopy were performed before and 1, 3, 6 and 12 months after optical urethrotomy. RESULTS All 22 patients voided freely on day 1 or 2 after urethrotomy. The stent slipped partially proximal to the stricture and had to be changed in only 1 patient. The stent was totally epithelialized in all but 1 patient at 6 months and had degraded in all at 12 months. The improvement in flow rate was maintained during followup except in 10 patients with stricture recurrence, which was outside the stent area usually close to the external sphincter in 7 and in the stent area in 3. All recurrences were treated with repeat optical urethrotomy and a new stent was inserted. Urinary infections developed in 2 patients and were successfully treated with oral antibiotics. CONCLUSIONS The self-expandable self-reinforced poly-l-lactic acid double spiral stent is a promising new method in the treatment of recurrent urethral strictures. There is no need to remove the device and no foreign material remains in the urethra. However, longer followup and controlled studies are needed to evaluate all benefits and side effects of this new treatment modality.

EXPANSION AND BIOABSORPTION OF THE SELF-REINFORCED LACTIC AND GLYCOLIC ACID COPOLYMER PROSTATIC SPIRAL STENT

PURPOSE Self-reinforced bioabsorbable stents can be made self-expanding due to the viscoelastic memory of the oriented bioabsorbable materials. A new self-expandable self-reinforced copolymer of lactic/glycolic acid, lactic/glycolic molar ratio 80:20 stent was developed to prevent postoperative urinary retention after procedures that induced prostatic edema. In in vitro experiments the expansion rate has been up to 100% during the first few hours at body temperature. We investigated the expansion rate and biodegradation of the self-reinforced lactic and glycolic acid copolymer prostatic spiral stent in vivo in the prostatic urethra. MATERIALS AND METHODS A total of 39 men, 52 to 84 years old, with lower urinary tract symptoms due to benign prostatic enlargement underwent interstitial laser coagulation of the prostate. A self-reinforced copolymer of lactic/glycolic acid, lactic/glycolic molar ratio 80/20 stent was inserted into the prostatic urethra at the end of the operation. The stent lumen diameter was 4.5 mm. The location and diameter of the lumen and degradation of the stent were studied with transrectal ultrasound at 1, 2, 4 and 6 months postoperatively. At 6 months patients underwent cystoscopy. RESULTS All except 1 patient voided on postoperative day 1. Mean lumen diameter was 7.4 mm. (range 6.2 to 8.2) at 1 month and 7.2 mm (range 6.2 to 7.5) at 2 months. At 4 months the stent was degraded into small pieces. No pieces of stent were found in the prostatic urethra on ultrasound or cystoscopy at 6 months. However, a portion of the spiral stent was found at the bottom of the bladder in 2 patients. CONCLUSIONS The speed and expansion rate of the self-reinforced copolymer of lactic/glycolic acid, lactic/glycolic molar ratio 80/20 stent was sufficient to lock the stent in place and ensure voiding in cases of edema induced bladder outlet obstruction. Strength retention greater than 2 months was long enough to avoid later impairments of voiding.

A bioabsorbable self-expandable, self-reinforced poly-l-lactic acid urethral stent for recurrent urethral strictures: Long-term results

BACKGROUND AND PURPOSE Biodegradable urethral stents have been used clinically for some years mainly in order to prevent postoperative urinary retention after minimally invasive thermotreatment of benign prostatic hyperplasia. We previously reported a 15-month-follow-up pilot study of a bioabsorbable self-expandable, self-reinforced poly-L-lactic acid (SR-PLLA) urethral stent in combination with optical urethrotomy in the treatment of recurrent urethral strictures. The present aim was to evaluate the long-term results of this new treatment modality. PATIENTS AND METHODS A series of 22 patients with severe urethral strictures (mean number of earlier urethrotomies 2.5) were involved. An SR-PLLA spiral stent with a bioabsorption time of 10 to 12 months was inserted into the urethra at the stricture site immediately after optical urethrotomy. Uroflowmetry, measurement of postvoiding residual urine, urine culture, and urethroscopy were performed preoperatively and at 1 and 3 months and then every 3 months up to 12 months, with subsequent follow-up visits every 6 months. The mean follow-up was 46 months. RESULTS The treatment was successful in 8 of the 22 patients (36%). Six recurrences were found within the stented area and 15 outside. Patients with failure have since been treated with several urethrotomies and repeat self-dilatations or free skin urethroplasties. CONCLUSIONS The results of the use of a bioabsorbable SR-PLLA urethral stent for the treatment of recurrent strictures were encouraging. Without this additional therapy, the recurrence rate of strictures might have been much higher. The main problem was sudden collapse of the stent, possibly induced by outer compression. A new generation of bioabsorbable stents is already under development.

A double-blind, randomized, placebo-controlled pilot study to investigate the effects of finasteride combined with a biodegradable self-reinforced poly L-lactic acid spiral stent in patients with urinary retention caused by bladder outlet obstruction from benign prostatic hyperplasia.

Objective To assess whether patients in acute urinary retention from benign prostatic enlargement can be treated with a combined therapy comprising finasteride and a bioabsorbable self‐reinforced poly l‐lactic acid (SR‐PLLA) urethral stent.

A randomised study to evaluate the efficacy of a biodegradable stent in the prevention of postoperative urinary retention after interstitial laser coagulation of the prostate.

Objective: Interstitial laser coagulation (ILC) of the prostate induces necrosis, oedema and increased risk for postoperative urinary retention. The present randomized study was carried out to investigate the feasibility and efficacy of a biodegradable self-reinforced polyglycolic acid (SR-PGA) stent in preventing postoperative urinary retention and the need for prolonged catheterization after ILC treatment. Material and methods: 35 males with benign prostatic enlargement (BPE) entered the study: 21 in the ILC + stent group and 14 in the ILC group without a stent. A suprapubic catheter was inserted for all patients and ILC was performed. The SR-PGA stent was inserted immediately after laser therapy in the stent group and kept open until the next morning when it was closed and the patient started trying to void. The suprapubic catheter was removed after voiding had started and the urinary bladder emptied adequately. Results: In the ILC + stent group voiding started on the first postoperative day in 17 patients and on the second day in 2 patients. Voiding was delayed in 2 cases: in 1 case due to inadequate length of the stent and in the other as a result of the stent placement being too proximal. There was 1 case of urinary retention due to early degradation of the stent. In the ILC-only group voiding started on average 6.1 days postoperatively. At 1 month follow-up, the mean peak urinary flow rate had increased significantly in the ILC + stent group (p < 0.05) but not in the ILC-only group (p = 0.26). Improvements in symptom scores were significant in both groups (p < 0.005) but in terms of the mean peak urinary flow rates at 6 months follow-up the improvement was significant only in the stent group (p < 0.05). Conclusions: The use of a SR-PGA stent enabled early voiding and is safe and effective in the treatment of postoperative urinary retention after ILC. The 3-4 week degradation time of the SR-PGA stent was too short for some patients. There is still a need for further development work to improve the stents and larger controlled studies to show the true value of biodegradable stents in the treatment of BPE.

Interstitial laser coagulation and biodegradable self-expandable, self-reinforced poly-L-lactic and poly-L-glycolic copolymer spiral stent in the treatment of benign prostatic enlargement.

BACKGROUND AND PURPOSE Interstitial laser coagulation of the prostate (ILCP) induces necrosis, edema, and an increased risk of postoperative urinary retention. The object here was to evaluate the efficacy, safety, and utility of a new self-expandable self-reinforced (SR) PLGA copolymer(lactic:glycolic ratio 80/20) spiral stent inserted after ILCP to promote voiding. The SR-PLGA stent has a degradation time of 2 to 2.5 months. PATIENTS AND METHODS Fifty men with a mean age of 70.5 years (range 52-85 years), suffering from lower urinary tract symptoms secondary to benign prostatic enlargement underwent ILCP. A suprapubic catheter was inserted, ILCP performed, and an SR-PLGA 80/20 spiral stent inserted on completion of the operation. The suprapubic catheter was removed when voiding commenced. As prophylactic antibiotic, ciprofloxacin was used in a single dose before ILCP, followed by trimethoprim or nitrofurantoin for 2 weeks. RESULTS All except three patients started to void on the first postoperative day. In two of the three cases, the stent had moved proximally and had to be relocated, whereafter voiding succeeded. The mean maximum and average flow rates increased, while DAN-PSS-1 symptom score and post voiding residual urine volume decreased statistically significantly. At 2 months, the stent was still intact in the urethra in all except three patients. At 4 months, it had been degraded into small fragments, and at 6 months, it had been completely eliminated. The only exceptions were three patients with an uncalcified piece of the stent in the bladder. Half of the patients had irritative symptoms caused at least partly by ILCP itself; 10% had asymptomatic urinary infection postoperatively. CONCLUSIONS The self-expandable SR-PLGA copolymer stent is safe and highly biocompatible. It ensures voiding in the case of temporary obstruction caused by prostatic edema. The degradation time is long enough in all patients to cover the need for postprocedure urinary drainage.

Viscoelastic memory and self-expansion of self-reinforced bioabsorbable stents

The possibility to decide the speed and rate of expansion of stents is of great clinical importance by reason of the varying requirements for different indications to use stents. Self-reinforced bioabsorbable stents can be made self-expanding owing to the viscoelastic memory of the material. Stents are stable at room temperature and expansion occurs at body temperature. The level at which the expansion stops depends on the material, crystallinity, initial diameter of spira and annealing temperature. The expansion rate can be estimated by logarithmic equation, if material, draw ratio and diameter of stent wire are constant. This is, however, possible only if processing parameters are constant. Based on the present results annealing temperature and expansion time were seen to be directly proportional to the expansion rate of the stent.

RABBIT MUSCLE AND URETHRAL IN SITU BIOCOMPATIBILITY PROPERTIES OF THE SELF-REINFORCED L-LACTIDE-GLYCOLIC ACID COPOLYMER 80: 20 SPIRAL STENT

PURPOSE A new type of self-reinforced L-lactide-glycolic acid copolymer, molar ratio 80:20, stent was developed. We evaluated the tissue biocompatibility properties of the new material. MATERIALS AND METHODS Rods made of self-reinforced L-lactide-glycolic acid copolymer were inserted into rabbit dorsal muscles and rods of latex or polyvinylchloride and silicone served as positive and negative controls, respectively. Urethral stents of self-reinforced L-lactide-glycolic acid copolymer and steel were inserted in situ via cystoscopy into the rabbit prostatic urethra. The animals were sacrificed after 2 weeks, 1, 2 and 3 months, respectively. In situ histological analysis was done. Tissue reactions around the implantation types were analyzed histologically and scored semiquantitatively. In addition, macroscopic analysis was done of the urethral in situ stents. RESULTS In rabbit muscle implantation test tissue reaction to the self-reinforced L-lactide-glycolic acid copolymer stent resembled that of negative control silicone. Less than moderate chronic inflammatory changes gradually subsided after 2 weeks. Foreign materials in the tissue and the reaction to these materials began to disappear after 1 month and at 3 months were completely absent. All rabbits fitted with the stent voided normally postoperatively. Self-reinforced L-lactide-glycolic acid copolymer stents were soft, partially fragmented and easily disintegrated when touched at 2 months, and were almost completely degraded at 3 months. The material did not encroach into the urethral wall macroscopically or microscopically. No calcification on the self-reinforced L-lactide-glycolic acid copolymer stents or bladder stone formation was seen. CONCLUSIONS The new self-reinforced L-lactide-glycolic acid copolymer 80:20 material is safe, highly biocompatible and suited for future clinical use. It is most appropriate for preventing postoperative urinary retention after most minimally invasive thermal treatments for benign prostatic hyperplasia.

Drug-eluting bioabsorbable stents – An in vitro study

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.