gms | German Medical Science

44. Jahrestagung der Deutschen Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen e. V. (DGPRÄC), 18. Jahrestagung der Vereinigung der Deutschen Ästhetisch-Plastischen Chirurgen e. V. (VDÄPC)

12.09. - 14.09.2013, Münster

Prolonged graft survival with a single injection of FK506 encapsulated hydrogel drug delivery system in allogeneic limb transplantation in rats

Meeting Abstract

  • presenting/speaker Radu Olariu - Universitätsspital Inselspital Bern, Klinik für Plastische und Handchirurgie, Bern, Schweiz
  • Franck Marie Leclère - Universitätsspital Inselspital Bern, Klinik für Plastische und Handchirurgie, Bern, Schweiz
  • Thusitha Gajanayake - Universitätsspital Inselspital Bern, Klinik für Plastische und Handchirurgie, Bern, Schweiz
  • Praveen Vemula - National Centre for Biological Sciences, Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, Indien, Indien
  • Mihai Constantinescu - Universitätsspital Inselspital Bern, Klinik für Plastische und Handchirurgie, Bern, Schweiz
  • Robert Rieben - Universität Bern, Departement Klinische Forschung, Bern, Schweiz
  • Esther Vögelin - Universitätsspital Inselspital Bern, Klinik für Plastische und Handchirurgie, Bern, Schweiz

Deutsche Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen. Vereinigung der Deutschen Ästhetisch-Plastischen Chirurgen. 44. Jahrestagung der Deutschen Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen (DGPRÄC), 17. Jahrestagung der Vereinigung der Deutschen Ästhetisch-Plastischen Chirurgen (VDÄPC). Münster, 12.-14.09.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. DocFV 81

doi: 10.3205/13dgpraec088, urn:nbn:de:0183-13dgpraec0881

Published: September 10, 2013

© 2013 Olariu et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Background: Vascularized composite allotransplantation (VCA), in particular hand transplantation, is deemed as the only method of regaining patient’s touch, function and appearance, which is inevitably unachievable with current prostheses. However, the issues related to immunosuppresion and its complications in a non-vital organ transplantation are reducing the applicability of this method. It is therefore of great interest to develop less aggressive, safer immmunosuppresion modalities in VCA. We hypothesized that the administration of FK506-encapsulated triglycerol monosterate (TGMS)-based hydrogels might be capable of releasing therapeutic concentration of FK506 over an extended period of time in a rat limb transplantation model.

Method: MHC-mismatched, Brown Norway (RT1n) to Lewis (RT1l) rat hind limb transplantation was performed. Rats were injected (subcutaneous) with a single dose of FK506 (7 mg) loaded into a hydrogel system or 7 mg of FK506 alone at post-operative day (POD) 1 into the transplanted limb.

Results: All allografts in the groups with TGMS as a vehicle control or no treatment groups were rejected with a median survival time (MST) of 11 days (n=4). Administration of FK506 at postoperative day (POD) 1 resulted in extended allograft survival with MST of 33 days (n=6). Interestingly, injection of TGMS encapsulated with FK506 into the transplanted limb resulted in prolonged graft survival with MST of >100 days (n=6).The termination point was defined as 100 days to analyze the allografts. Plasma FK506 levels were significantly higher in the FK506 alone-treated group at day 3 compared to the TGMS-FK506-treated group (p<0.01). Although persistent FK506 was detected in the TGMS-FK506-treated group, drug concentration was significantly declined in the FK506 alone-treated group at day 11 and FK506 was not detected at rejection. However, TGMS-FK506-treated group had 0.38 ng/ml at 100 d. Injection of TGMS-FK506 into the contralateral limb prolonged the graft survival with MST of 75 d (n=5). Swelling and depot formation ability of the TGMS hydrogels were significantly more efficient in the transplanted limb compared with the contralateral limb as confirmed by palpation test and ultrasonography. The size of the drug depot on transplanted limb was 0.68 cm3 compared to the size of 0.12 cm3 in the contralateral limb at POD 21.

Conclusion: For the first time, we report that an injected FK506-encapsulated hydrogel system is capable in prolonging allograft survival in a VCA model. Therefore, hydrogel based drug delivery might be a promising approach in enhancing therapeutic window and reducing side effects of current immunosuppressive drugs.