Biodegradable, Self-Reinforced, Self-Expandable Lactic and Glycolic Acid (SR-PLGA80/20) Copolymer Spiral Prostatic Stent: Analysis of mechanical and biological properties and clinical results

Abstract

Biohajoavat materiaalit ovat olleet käytössä urologisessa kirurgiassa 1990-luvun puolivälistä lähtien. PLGA 80/20 on L-laktidin ja glykolidin muodostama uusi kopolymeeri (kehitetty yhteistyössä Tampereen Teknillisen yliopiston ja Tampereen yliopistollisen sairaalan urologian yksikön kanssa).

Väitöskirjatyö koostuu 5 osatyöstä jossa analysoitiin tämän uuden materiaalin mekaanisia ja biologisia ominaisuuksia sekä kliinisiä tuloksia.

Osatyössä I analysoitiin biohajoavan PLGA80/20 prostatastentin viskoelastista muistia sekä laajenemista koeputkiolosuhteissa ja verrattiin uutta materiaalia PGA ja PLLA materiaalin vastaaviin ominaisuuksiin. PLGA 80/20 materiaali laajeni nopeasti ja enemmän kuin muut polymeerit ja lopullisen laajenemisen PLGA saavutti kolmessa päivässä.

Osatyössä II tutkittiin keinoputkiolosuhteissa uuden PLGA stentin ja metallisen kullalla päällystetyn Prostakath ja nikkeli-titaniumista valmistetun Memokath stentin karstoittumista sekä PLGA materiaalin kompressiokestävyyttä standardi Ph-olosuhteissa steriilissä keinovirtsassa.Tulokset analysoitiin tietokoneohjelmalla.Koe-asetelma osoitti että PLGA materiaali omaa erinomaiset mekaaniset ominaisuudet.

Osatyössä III PLGA materiaaln kudossoveltuvuutta ja biohajoamista tutkittiin kanin selkälihasimplanttikokeilla ja soveltuvuutta prostaattiseen urethraan selvitettiin asettamalla laajennin kanin eturauhasen kohdalle virtsaputkeen. PLGA materiaalin kudossoveltuvuus osoittautui erinomaiseksi kummassakin analyysissa.

Osatöissä IV ja V käsiteltiin PLGA -materiaalin sopivuutta kliiniseen käyttöön ja PLGA materiaalin laajenemisominaisuuksia potilaskäytössä.Tutkimustulosten mukaan uusi PLGA materiaali osoittautui turvalliseksi, kudossoveltuvuudeltaan ja karstoittumisominaisuuksiltaan erinomaiseksi ja soveltunee siten turvotusta aiheuttavien eturauhastoimenpiteiden kanssa käytettäväksi.

In the development of bioabsorbable stents, the goal is to find the right material and suitable construction and processing methods to create optimal properties for an implant for a specific application. New therapy modes are continuously being accepted, and the use of biodegradable materials in these methods should be intensively investigated. Also the material development of biodegradable polymers will offer new alternatives and better possibilities to tailor material properties for specific applications. The aim of the present study was to evaluate the viscoelastic memory and expansion, mechanical and encrustation properties of a new biodegradable polylactic copolymer material (I, II, III, IV) and also the safety, feasibility and efficacy of biodegradable urethral stents in vivo (III, IV, V).

In the analysis of viscoelastic memory and self-expansion properties the SR-PLGA 80/20 spiral stent proved to have a 100 % in vitro expansion rate capacity during three days. The expansion was faster and greater than that of other self-reinforced polymers. The analysis proved that the new helical spiral stent possesses ideal mechanical properties. The compression strength of SR-PLGA started to decrease after 6 weeks and was 35 % of baseline after 8 weeks. The compression strength is suited to most indications for temporary stenting in urology. The encrustation properties of SR-PLGA 80/20 were superior to nitinol and gold plated stainless steel materials. At 8 weeks' follow-up areas covered by encrustation were respectively 0.12 %, 28.4 % and 4.1 %.

The biocompatibility of the SR-PLGA stent material was evaluated in a muscle implantation test according to the recommendations of ISO. In addition, urethral in situ implantation of the stents was used in the analysis of biological safety. The biocompatibility properties of the new SR-PLGA 80/20 material proved to be good in both analyse. In the in situ study SR-PLGA 80/20 urethral stents started to disintegrate macroscopically at 2 months and were almost completely degraded by 3 months. No calcification and bladder stone formation was seen in the PLGA group.

In the clinical studies 50 men evincing lower urinary tract symptoms due to benign prostatic hyperplasia underwent ILCP in a pilot study without a control group. The ILCP thermo therapy was perfomed under spinal anesthesia and an SR-PLGA urethral spiral stent was inserted into the prostatic urethra after the procedure. Expansion and biodegradation properties, voiding and urinary symptoms were analysed at 1, 2, 4 and 6 months thereafter. The stent expanded rapidly and did not shorten in expansion. Voiding commenced on the first postoperative day in all except three patients and in two cases relocation of the stent had to be done. The mean maximum and average flow rates increased while the DAN-PSS-1 symptom score and post-voiding residual urine decreased statistically significantly. The fragmentation of the spiral stent started after 2 months and at 4 months small fragments in prostatic urethra were seen in transrectal ultrasound. At 6 months cystoscopy the defected no stent fragments in the prostatic urethra. Five patients (10 %) had asymptomatic urinary infection postoperatively. No urethral strictures or urinary stones were seen during six months' follow-up.

With material and stent configuration selection and manufacture processing the intended, near ideal properties for urinary tract stents could be achieved in this project. The speed and rate of expansion of the new SR-PLGA 80/20 material were sufficient to lock the stent in place and ensure voiding in the case of oedema induced bladder outlet obstruction after ILCP. The strength retention time of more than 2 months was long enough to avoid later impairment of voiding.

By merit of the ideal degradation time the SR-PLGA prostatic stents might prove eminently most suitable for the prevention of postoperative retention after different types of thermal treatment of prostatic hyperplasia or after brachytherapy of prostatic cancer. This kind of stent is also suitable for the testing of voiding problems before other more radical prostatic operations.