Delivery of Rapamycin Using In Situ Forming Implants Promotes Immunoregulation and Vascularized Composite Allograft Survival.

Sutter, Damian; Dzhonova, Dzhuliya Vihrenova; Prost, Jean-Christophe; Bovet, Cedric; Banz Wälti, Yara; Rahnfeld, Lisa; Leroux, Jean-Christophe; Rieben, Robert; Vögelin, Esther; Plock, Jan Alexander; Luciani, Paola; Taddeo, Adriano; Schnider, Jonas Thomas (2019). Delivery of Rapamycin Using In Situ Forming Implants Promotes Immunoregulation and Vascularized Composite Allograft Survival. Scientific Reports, 9(1), p. 9269. Nature Publishing Group 10.1038/s41598-019-45759-y

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Vascularized composite allotransplantation (VCA), such as hand and face transplantation, is emerging as a potential solution in patients that suffered severe injuries. However, adverse effects of chronic high-dose immunosuppression regimens strongly limit the access to these procedures. In this study, we developed an in situ forming implant (ISFI) loaded with rapamycin to promote VCA acceptance. We hypothesized that the sustained delivery of low-dose rapamycin in proximity to the graft may promote graft survival and induce an immunoregulatory microenvironment, boosting the expansion of T regulatory cells (T). In vitro and in vivo analysis of rapamycin-loaded ISFI (Rapa-ISFI) showed sustained drug release with subtherapeutic systemic levels and persistent tissue levels. A single injection of Rapa-ISFI in the groin on the same side as a transplanted limb significantly prolonged VCA survival. Moreover, treatment with Rapa-ISFI increased the levels of multilineage mixed chimerism and the frequency of T both in the circulation and VCA-skin. Our study shows that Rapa-ISFI therapy represents a promising approach for minimizing immunosuppression, decreasing toxicity and increasing patient compliance. Importantly, the use of such a delivery system may favor the reprogramming of allogeneic responses towards a regulatory function in VCA and, potentially, in other transplants and inflammatory conditions.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery
08 Faculty of Science > Departement of Chemistry and Biochemistry
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery > Hand Surgery
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery > Plastic, Reconstructive and Aesthetic Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Handchirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Herz und Gefässe
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50

UniBE Contributor:

Sutter, Damian; Banz Wälti, Yara; Rahnfeld, Lisa; Rieben, Robert; Vögelin, Esther; Plock, Jan Alexander; Luciani, Paola; Taddeo, Adriano and Schnider, Jonas Thomas

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

2045-2322

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Veronika Picha

Date Deposited:

16 Jul 2019 13:33

Last Modified:

21 Jul 2019 02:40

Publisher DOI:

10.1038/s41598-019-45759-y

PubMed ID:

31239498

BORIS DOI:

10.7892/boris.131623

URI:

https://boris.unibe.ch/id/eprint/131623

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