Tissue engineered testicular prostheses with prolonged testosterone release.
OBJECTIVE
Bilateral anorchia, either congenital or acquired, often requires testicular prostheses placement and testosterone supplementation. 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.


METHODS
Chondrocytes, harvested from bovine articular cartilage, were seeded on testicular shaped polymer scaffolds at a concentration of 100 x 10(6) ml(-1). The scaffolds were maintained in a bioreactor for 4 weeks to form cartilage tissue. Subsequently, testosterone enanthate (100 microg) was injected into the central hollow space of each testicular prosthesis, and maintained for 40 weeks in culture. A sample of the medium was collected every 2 days for testosterone assays. Another group of ex vivo engineered testicular prostheses was implanted into the scrotal space of castrated athymic mice (n = 10). Intratesticular injection of testosterone enanthate was made into each prosthesis at a concentration of 100 microg. Control groups consisted of animals with castration only (n = 8) and sham operations (n = 5). Testosterone levels were measured prior and 2 weeks after castration, 1 day after testosterone administration, and weekly up to 14 weeks. The engineered testicular prostheses were retrieved at sacrifice for histomorphological and immunocytochemical analyses.


RESULTS
Milky white cartilage testicular protheses were formed by 4 weeks. The ex vivo 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 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 1 and a continued physiologic range during the entire study period. Histologically, the retrieved testicular implants showed mature chondrocytes with a hollow center in each prosthesis.


CONCLUSIONS
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 patients who require testicular prostheses and chronic hormone supplementation.
Hospital Infantil de Mexico "Federico Gomez", Mexico City, Mexico.
Atlantida M
AM
Raya-Rivera
Carlos
C
Baez
Anthony
A
Atala
James J
JJ
Yoo
D000818:Animals; D019149:Bioreactors; D002358:Cartilage, Articular / Q000166:cytology; D002417:Cattle; D019902:Chondrocytes / Q000166:cytology; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000637:transplantation; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009919:Orchiectomy; D019736:Prostheses and Implants; D019919:Prosthesis Implantation; D012611:Scrotum / Q000601:surgery; D013737:Testis / Q000378:metabolism* / Q000601:surgery*; D013739:Testosterone / Q000378:metabolism*; D023822:Tissue Engineering / Q000379:methods*
D013739:Testosterone; D003094:Collagen