Tissue Engineered Testicular Prostheses With Prolonged Testosterone Release

摘要

Young soldiers with testicular tissue injury may require testicular prostheses placement and testosterone supplementation to maintain male sexual characteristic. Several types of testosterone compounds and various modes of hormone delivery are currently used clinically, however, their pharmacokinetic properties are not ideal. In this study we explored the possibility of creating hormone releasing testicular prostheses that could continuously supply and maintain physiologic levels of testosterone in vivo over time. Chondrocytes harvested from bovine articular cartilage were seeded on testicular shaped polymer scaffolds at a concentration of 100 x 10(exp 6) /ml. Scaffolds were maintained in a bioreactor for 4 weeks to form cartilage tissue. Subsequently, testosterone enanthate (100 microgram) was injected into the central hollow space of each testicular prosthesis. Some prostheses were observed in vitro, and another group was implanted into the scrotal space of castrated athymic mice (n=10). The implanted prostheses showed an initial burst effect of testosterone followed by a broad plateau for 16 weeks (> 500 ng/dl) and a decreased level of testosterone until 40 weeks. The testosterone levels were physiologic throughout the 40 weeks and the entire testosterone released was calculated as 60% of the injected volume. The circulating testosterone levels in the protheses implanted animals demonstrated a maximum peak on day one and a continued physiologic range during the entire study period. This study demonstrates that engineered cartilage testis can be created in bioreactors, can be implanted in vivo, and can release testosterone for a prolonged period. Furthermore, the levels of testosterone release can be maintained within the physiologic range. Periodic reinjection may potentially provide permanent physiologic hormonal replacement. This novel technology may be beneficial for injured soldiers who require testicular prostheses and chronic hormone supplementation.