Experimental Study Of Spiral Biodegradable Ureteral Stent

Ureteral stent is conventionally used in urological surgery as a medical equipment for the therapy of ureteral stricture and the healing of anastomosis, preventing various complications. At present, clinical ureteral stesnt is mainly composed of indegradable materials such as silicone and polyurethane. Being not indwelling in the body for a long time, these indegradable stents need to be taken out with second operation. So, it is very necessary for the development of a biodegradable ureteral stent.Objective:Prepared an X-ray-displayed spiral biodegradable ureteral stent with polylactic acid and barium sulfate, and evaluated its degradation in vitro and biological compatibility. Established a injury model of Beagle's ureter by firearms shrapnel, then implanted ureteral stent into the ureteral to explore corresponding characteristics of experimental study of animal. We wanted to provide a new type of medical equipment for ureteral injury to resolve the problem of second operation for non-degradable stent, and provied information of experimental study of animal for the clinical treatment of ureteral injury.Methods:1. Preparation of spiral biodegradable ureteral stentA mixture of PLLA, PDLLA and barium sulfate in a certain mass ratio were blended to manufacture films by solvent evaporation method. By the followed incision intertwist and drying, stents were prepared, which were divided into groups A, B, C and D according to the mass ratio of 100 / 0, 75 / 25, 50 / 50, 0 / 100 between PLLA and PDLLA.2. Characterization of degradation of spiral biodegradable ureteral stents in vitroUreteral stents about 30 mm long were immersed in the urine from healthy volunteers, which was uptated every other day, oscillating at 60 rpm at 37℃.(1) General morphology: Stents were observed with naked eye from 0 to10 weeks.(2) Expansion rate: The diameter of stents were measured with electronic vernier caliper at 0, 2, 4, 6, 8 and 14 days, then expansion rate was calculated.(3) Morphology and elemental analysis: Morphology and elemental analysis were done at 0, 1, 2, 3, 4, 5 and 6 weeks by scanning electron microscopy(SEM) and energy dispersive spectrograph (EDS) .(4) molecular and bio-degradation rate: Molecular was measured with Ubbelohde viscometer at 0 and 4 weeks, then the bio-degradation rate was calculated.3. Characterization of biological compatibility of spiral biodegradable ureteral stent Films were prepared for the convenience of this characterization, with the same components of the corresponding groups of stents.(1) Hydrophilicity: The contact angle of the films was detected, which was used to evaluate the hydrophilicity of stents.(2) Cytocompatibility: Human vascular smooth muscle cells (VSMC) was seeded in a same density on the four groups of films which were sterilized by 60Co irradiation and co-cultured for some time. MTT test was done at 3, 5 and 7 days, respectively.(3) Histocompatibility: After sterilized by 60Co irradiation, films were implanted into the subcutaneous tissue of New Zealand white rabbits which would sacrifice at 4th and 15th days for the histological analysis.4. Animal experimental study on spiral biodegradable ureteral stentFirst, injury models of nine Beagle dogs'ureter by firearms shrapnel were established, which were divided into three groups according to the time of sacrifice(40, 80 and 120 days) after operation. Then, 50 mm long biodegradable ureteral stents of C-group were implanted into one side of the animal's ureter, and indegradable double-J ureteral stents were implanted on the other side as comparison. Finally, analysis of imaging, materials science and histology were performed.Results:1. Characterization of degradation of spiral biodegradable ureteral stents in vitro The preparation of ureteral stents in our study was easy and didn't need any large-scale instrument and equipment, to make the method more scientific and operational. large-scale process equipment, user-friendly and take into account the scientific and operational2. Characterization of degradation of spiral biodegradable ureteral stents in vitro(1) General morphology: The color of ureteral stent varied from white to light brown with the increasing degradation, forming crystallization on the surface. Group D lost its general morphology at 7th week, while the remaining three groups were as late as 10th week.(2) Expansion rate: The expansion rate of group C was the largest, group D inferior, and the ones of groups A and B were very small. All Expansion rates stabilized at the 8th day.(3) Morphology and elemental analysis: Holes occurred on the surface of stent with its degradation gradually, the number and size of which increased gradually too. In the process of degradation, calcium deposited on the surface of stent.(4) Molecular and bio-degradation rate: Moleculars measured at 4th week of groups A, B, C and D decreased gradually, namely that the bio-degradation rates of groups A, B, C and D increased gradually. 3. Characterization of biological compatibility of spiral biodegradable ureteral stent(1) Hydrophilicity: The contact angle of groups A, B, C and D increased gradually, and corresponding hydrophilicity decreased gradually.(2) Cytocompatibility: MTT results showed that every group had a good cytocompatibility, especially groups A, B and C, the value of MTT of which was bigger than groups tissue culture plate(TCP) and D remarkablely.(3) Histocompatibility: All the four groups had good histocompatibility , no significant inflammatory response was found both in 4th and 15th samples.4. Animal experimental study on spiral biodegradable ureteral stentBiodegradable stent with the occurrence of double-J tube did not shift, fall off, no obvious obstruction, have played a supporting role in drainage; have a good biocompatibility, no significant inflammatory response ; biodegradable stent was superior to the performance of anti-calculus double J tube, and with the implantation time, the gradual degradation of biodegradable stents, which do not degrade double-J tube.Conclusions:We prepared an X-ray-displayed spiral biodegradable ureteral stents with PLA and barium sulfate, and evaluated by characterization of degradation in vitro and biological compatibility, and experimental study of animal, proving that group C (the mass ratio of PLA and barium sulfate was 4:1, PLLA and PDLLA was 50:50) was X-ray-displayed, playing a important role in drainage with good biological compatibility. At the same time, it could inhibit the formation of ureteral calculi, and degradate gradually with the time of implantation. Our study need to be researched for a long time still. If the characteristics of the biodegradable ureteral stent were improved further, it was possible to apply to clinical research.