A single localized dose of enzyme-responsive hydrogel improves long-term survival of a vascularized composite allograft

Gajanayake, Thusitha; Olariu, Radu; Leclère, Franck-Marie Patrick; Dhayani, Ashish; Yang, Zijiang; Bongoni, Anjan; Banz Wälti, Yara; Constantinescu, Mihai Adrian; Karp, Jeffrey M.; Vemula, Praveen Kumar; Rieben, Robert; Vögelin, Esther (2014). A single localized dose of enzyme-responsive hydrogel improves long-term survival of a vascularized composite allograft. Science translational medicine, 6(249), 249ra110. American Association for the Advancement of Science 10.1126/scitranslmed.3008778

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Currently, systemic immunosuppression is used in vascularized composite allotransplantation (VCA). This treatment has considerable side effects and reduces the quality of life of VCA recipients. We loaded the immunosuppressive drug tacrolimus into a self-assembled hydrogel, which releases the drug in response to proteolytic enzymes that are overexpressed during inflammation. A one-time local injection of the tacrolimus-laden hydrogel significantly prolonged graft survival in a Brown Norway-to-Lewis rat hindlimb transplantation model, leading to a median graft survival of >100 days compared to 33.5 days in tacrolimus only-treated recipients. Control groups with no treatment or hydrogel only showed a graft survival of 11 days. Histopathological evaluation, including anti-graft antibodies and complement C3, revealed significantly reduced immune responses in the tacrolimus-hydrogel group compared with tacrolimus only. In conclusion, a single-dose local injection of an enzyme-responsive tacrolimus-hydrogel is capable of preventing VCA rejection for >100 days in a rat model and may offer a new approach for immunosuppression in VCA.

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 > Plastic, Reconstructive and Aesthetic Surgery
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery > Hand Surgery
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery
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 > Forschungsgruppe Angiologie
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) > Forschungsbereich Mu50 > Forschungsgruppe Plastische Chirurgie
09 Interdisciplinary Units > Microscopy Imaging Center (MIC)

UniBE Contributor:

 Gajanayake, Thusitha, Olariu, Radu, Leclère, Franck-Marie Patrick, Yang, Zijiang, Bongoni, Anjan, Banz Wälti, Yara Sarah, Constantinescu, Mihai Adrian, Rieben, Robert, Vögelin, Esther

Subjects:

 600 Technology > 610 Medicine & health

ISSN:

 1946-6234

Publisher:

 American Association for the Advancement of Science

Language:

 English

Submitter:

 Jörg Arnoldi

Date Deposited:

 05 Sep 2014 09:06

Last Modified:

 02 Mar 2023 23:25

Publisher DOI:

 10.1126/scitranslmed.3008778

PubMed ID:

 25122638

BORIS DOI:

 10.7892/boris.58117

URI:

 https://boris.unibe.ch/id/eprint/58117

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