Tero Välimaa

Biodegradation of the copolymeric polylactide stent : Long-term follow-up in a rabbit aorta model

The behavior of biodegradable polylactide as a stent material has not yet been fully established in small vessels such as arteries with a diameter <3 mm. The aim of this study was to investigate the long-term effect of a copolymeric polylactide (PLA96) stent. Appropriately sized spiral PLA96 stents were implanted into the infrarenal aortas of 20 rabbits. Intraoperative systemic heparinization (150 IU/kg), perioperative subcutaneous enoxaheparin sodium (10 mg), ticlopidine (250 mg/day) for 1 month, and acetosalicylic acid (12.5 mg/day) were continuously administered. Animals were euthanized according to a fixed timetable for up to 34 months for histologic and scanning-electron-microscopic assessment. Endothelialization was complete within 1 month. In 2 of the 3 aortas sampled 3 months after implantation, a mild inflammatory reaction was visible, with no sign of granulomatous or foreign-body reaction in the vessel wall. Instead, in 1 sample examined at the same time point, neointimal chondroid metaplasia was detected. After 6 months, inflammatory reaction declined in the vessel wall. Hydrolyzation of the stent was histologically evident at 12 months, with mild foreign-body reaction detectable in 2 of 5 aortas sampled at this time point. The stent disintegrated without fragmentation by 24 months, as it was gradually replaced by fibrosis. The vessel lumen remained patent at all time points. We conclude that the PLA96 stent degraded with minimal tissue response within 24 months. PLA96 may thus be a promising stent core material for small vessels in the future, although further investigation is needed to establish its final biocompatibility.

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.

Biodegradable self-reinforced polyglycolic acid spiral stent in prevention of postoperative urinary retention after visual laser ablation of the prostate-laser prostatectomy

PURPOSE The efficacy and safety of a new biodegradable (self-reinforced polyglycolic acid) spiral stent in securing free voiding despite edema after visual laser ablation of the prostate were studied. MATERIALS AND METHODS A biodegradable spiral stent was inserted into the prostatic urethra in 22 patients immediately after visual laser ablation of the prostate. Uroflowmetry, measurement of residual urine volume, urine culture, cystoscopy and assessment of symptomatic improvement were done before, and 1, 3 and 6 months after visual laser ablation of the prostate. RESULTS All 22 patients voided freely on day 1 or 2 after visual laser ablation of the prostate. However, 4 patients later had urinary retention due to a short spiral or too rapid spiral degradation. Half of the patients experienced a transient decrease in flow with some obstructive symptoms at 3 weeks that lasted 1 to 2 weeks. At 4 weeks all spirals were degraded and 3 patients had a positive urine culture. The maximum flow rate increased and the residual urine volume decreased significantly concomitantly with significant symptomatic improvement. CONCLUSIONS The self-reinforced polyglycolic acid spiral stent can effectively and safely prevent postoperative urinary retention after visual laser ablation of the prostate.

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.

A Randomized Study to Compare Biodegradable Self-reinforced Polyglycolic Acid Spiral Stents to Suprapubic and Indwelling Catheters After Visual Laser Ablation of the Prostate

PURPOSE A randomized controlled study was done to evaluate the efficacy of the self-reinforced polyglycolic acid spiral stent compared to a suprapubic catheter, and combined suprapubic and indwelling catheters in the prevention of urinary retention after visual laser ablation of the prostate. MATERIALS AND METHODS We studied 72 men with benign prostatic hyperplasia who underwent placement of a suprapubic catheter and visual laser ablation of the prostate. In 27 men in group 1 the self-reinforced polyglycolic acid spiral stent was inserted into the prostatic urethra after visual laser ablation of the prostate, while 23 in group 2 received no other devices. In 22 men in group 3 an indwelling catheter was left in situ for an average of 6.5 days. RESULTS Voiding began 1 or 2 days postoperatively in 20 of 27 patients (median 1 day) in group 1, and 8 of 23 (median 6 days) in group 2. In 16 of 22 men in group 3 voiding began 1 or 2 days (median 6) after removal of the indwelling catheter. Improvements in patient weighted symptom score, mean peak urinary flow rate and post-void residual volume were significant (p < 0.001) at 6 months of followup in all groups. The overall infection rate was 30%. CONCLUSIONS The self-reinforced polyglycolic acid spiral stent is superior to the suprapubic catheter alone, and to combined indwelling and suprapubic catheters for the treatment of postoperative urinary retention after laser therapy, offering possibilities for shorter catheterization time.

The morphological, in situ effects of a self-reinforced bioabsorbable polylactide (SR-PLA 96) ureteric stent; an experimental study.

PURPOSE The present study was done to evaluate the biocompatibility of a new biodegradable double helical spiral self-reinforced poly-L, D-lactide copolymer (L/D ratio 96/4, SR-PLA96) ureteric stent. MATERIALS AND METHODS In sixteen dogs, the right ureter was cut transversally, sutured and stented with a 50 mm. long SR-PLA 96 stent. In eight dogs, left ureter was similarly operated and stented with a double-J pigtail stent (C-Flex, Cook Urological Inc.), while eight remaining ureters served as plain controls. Urine was analyzed for signs of infection. The dogs were terminated at 6, 12 and 24 weeks postoperatively and the ureters dissected to find persistent SR-PLA 96 particles or local ureteric changes. Histologic samples were taken at three levels of dissected ureters in contact with the stent. RESULTS C-Flex and SR-PLA 96 materials were well tolerated. Both of these induced only minimal ureteral wall edema, epithelial hyperplasia, epithelial destruction and inflammatory cell reaction. In SR-PLA 96 stented ureters the tissue reaction subsided after the degradation of the device. CONCLUSIONS SR-PLA 96 spiral stent is regarded highly compatible and SR-PLA 96 might be a suitable material for a partial ureteric stent. Biodegradation of a SR-PLA 96 stent makes stent removal unnecessary.

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 new biodegradable stent for the pancreaticojejunal anastomosis after pancreaticoduodenal resection: in vitro examination and pilot experiences in humans.

We sought to develop a biodegradable pancreatic stent that could be easily placed at operation into the human pancreatic duct and the degradation of which could be easily followed up. Spiral-shaped, gamma-sterilized stents were manufactured of 0.4-mm polylactide wire in which there was added 23 weight-% barium sulfate. The biodegradability of the stents was studied in vitro at two different pH values, the first resembling that of pancreatic juice and the other that of bile. The effects of enzymoactivity in the test solution and the composition of the stents (with or without barium addition) also were tested. These kinds of stents have been experimented with in two pilot patients. Degradation of the stents occurred from 24 to 52 weeks of incubation. Alkaline milieu together with the presence of pancreatic enzyme made the stents degrade twice as fast as when either alkaline milieu or enzyme was present. In the milieu resembling pancreatic juice, barium sulfate had no effect on the degradation time. Neither of the pilot patients had any postoperative complications. Biodegradable, x-ray–positive stents degrade faster in pancreatic than in biliary milieu. Their safety and efficacy in human pancreaticojejunal anastomoses need further study.

Mechanical properties and in vitro degradation of bioresorbable knitted stents

- The aim of this study was to characterize the mechanical properties and in vitro degradation of bioresorbable knitted stents. Each stent was knitted using a single self-reinforced fibre made out of either PLLA or 96L/4D PLA or 80L/20G PLGA. The mechanical and physical properties of the fibres and stents were measured before and after gamma sterilization, as well as during in vitro degradation. The mechanical properties of the knitted stents made out of bioresorbable fibres were similar to those of commercially available metallic stents. The knitting geometry (loop height) had a marked effect on the mechanical properties of the stents. The rate of in vitro degradation in mechanical and physical properties for the PLLA and 96L/4D PLA stents was similar and significantly lower than that of the 80L/20G PLGA stents. The 80L/20G PLGA stents lost about 35% of their initial weight at 11 weeks. At this time, they had lost all their compression resistance strength. These data can be used as a guideline in planning further studies in vivo.