The injection of bulking substances has been proposed as a new therapy to treat urinary incontinence and vesicoureteral reflux. Our previous study demonstrated that poly(lacticco-glycolic acid) (PLGA) microspheres have the potential to serve as a bulking agent for urological injection therapies. Hybrid tissues exhibiting a bulking effect were formed in vivo by PLGA microsphere injection, but long-term volume stability was not proven. In this study, we hypothesized that the biodegradation rate of the bulking substance (polymer microspheres) would affect the duration of volume conservation of the induced hybrid tissue. To test this hypothesis, rapidly degrading 75:25 PLGA microspheres and slowly degrading poly(L-lactic acid) (PLLA) microspheres were used as injectable bulking agents for the injection therapy. In vitro degradation tests showed that the mass losses of PLLA and PLGA were 16 and 96% of the initial masses, respectively, at 30 weeks. PLLA and PLGA microspheres were injected into the subcutaneous dorsum of mice. Both types of microspheres were easily injectable through 24-gauge needles. Histological examinations at various time points indicated that host cells from the surrounding tissues migrated to the spaces between both types of injected microspheres and formed new hybrid tissue structures. Lymphocyte migration was noted around the implanted PLGA and PLLA microspheres, but the inflammatory reaction diminished with time. Importantly, the volume of the PLLA hybrid tissues slowly decreased to 52% of the initial volume at 12 months and maintained that volume until 18 months, whereas the volume of the PLGA hybrid tissues rapidly decreased to 22% at 6 months, and the PLGA hybrid tissues disappeared at 11 months. These results show that the biodegradation rate of the bulking substance may be useful for controlling the duration of volume conservation of the induced hybrid tissue.

Injection of bulking substances has been introduced as a new therapy to treat urinary incontinence and vesicoureteral reflux. Currently available bulking substances for the injection therapies include liquid or particulated silicone, collagen gel, and polytetrafluoroethylene paste. However, these materials have shown shortcomings such as inflammation, rapid volume decrease, and particle migration to distant organs. In the present study, we evaluated poly(lactic-co-glycolic acid) (PLGA) microspheres as a potential injectable bulking agent for the injection therapies. PLGA microspheres (52 m in average diameter) were injectable through various gauges of needles, as the injected microspheres showed no tendency to obstruct the needles and microsphere size exclusion was not observed upon injection through the needles. After injection of PLGA microspheres into the subcutaneous dorsum of mice, inflammation, new tissue volume change, and microsphere migration were examined. Host cells from the surrounding tissues migrated to the implanted microspheres and formed new hybrid tissue structures. The volume of the newly generated tissues was maintained approximately constant for 7 weeks. Histological analyses showed no evidence of migration of the implanted microspheres to the distant organs. In summary, PLGA microspheres were injectable and able to induce a new hybrid tissue formation without initial volume decrease or particle migration. These preliminary results suggest that this material may be a potentially useful bulking agent for urological injection therapies.

Endoscopic injection of bulking agents has been gaining attention as a therapy for urinary incontinence and vesicoureteral reflux because this therapy is simpler, less operation time-consuming and less painful than traditional surgical operations. The ideal bulking agent for the injection therapies must be easily injectable, biocompatible, volume-stable, non-antigenic and non-migratory. We evaluated poly(lactic-co-glycolic acid) (PLGA) microspheres as an injectable bulking agent for urologic injection therapies. To determine whether PLGA microspheres meet the requirements of an ideal bulking agent, PLGA microspheres were injected into the submucosal sites of a rabbit bladder wall. The microspheres were easily injectable. Two and five weeks post-implantation, histological examinations indicated that host cells from the surrounding bladder tissues migrated to the space between the injected microspheres and formed new hybrid tissue structures. Lymphocyte migration was noted around the implanted microspheres, but the inflammatory reaction diminished at 5 weeks. The hybrid tissue volume did not significantly decrease over time. There was no evidence of microsphere migration to the distant organs. Although long-term studies are needed to evaluate the therapeutic potential of this method, these preliminary results suggest the possibility of PLGA microspheres as a potentially useful injection material for urinary injection therapies.