Implantable vascularized endocrine constructs for clinically scalable insulin delivery
Extrahepatic islet transplantation offers a clinically attractive alternative to intrahepatic delivery, but its success has been constrained by inadequate vascularization and lack of a supportive microenvironment. To address this, we engineered vascularized endocrine constructs (VECs) by coencapsulating pancreatic islets with human blood outgrowth endothelial cells in a good manufacturing practice-compliant amniotic membrane hydrogel (Amniogel). Amniogel provides extracellular matrix-bound prosurvival cues that enhance islet viability and function and promote endothelial self-assembly into vascular networks-improving β-cell gap junction coupling and restoring dynamic glucose-responsive insulin secretion. After subcutaneous implantation in diabetic mice, VECs anastomosed with host vessels and reestablished normoglycemia, outperforming nonvascularized controls. Furthermore, Amniogel impeded chemokine-driven cytotoxic T cell migration and delayed β-cell killing in vitro in a concentration-dependent manner. This integrative strategy, combining a scalable biological scaffold with vascularization and intrinsic barrier properties that may limit early immune cell infiltration, offers a clinically relevant path toward durable β-cell replacement therapies in type 1 diabetes.
Authors
- Juliette Bignard (ORCID: https://orcid.org/0009-0006-8519-0182)
- Reine Hanna
- Alessia Cucci (ORCID: https://orcid.org/0000-0002-5003-831X)
- Philippe Compagnon (ORCID: https://orcid.org/0000-0002-7423-5887)
- Mohsen Honarpisheh (ORCID: https://orcid.org/0000-0003-3002-7442)
- Antonio Citro
- Kevin Bellofatto (ORCID: https://orcid.org/0000-0001-7961-4539)
- Marie Cohen (ORCID: https://orcid.org/0000-0003-4621-5464)
- Antoine Marteyn (ORCID: https://orcid.org/0000-0003-2176-3595)
- Fanny Lebreton (ORCID: https://orcid.org/0000-0002-3175-0205)
- Begoña Martínez de Tejada (ORCID: https://orcid.org/0000-0001-5737-3586)
- Ekaterine Berishvili (ORCID: https://orcid.org/0000-0002-7969-1937)
- Masoud Hasany (ORCID: https://orcid.org/0000-0002-1407-257X)
- Xavier Charmetant (ORCID: https://orcid.org/0000-0002-2162-5873)
- Antonia Follenzi (ORCID: https://orcid.org/0000-0001-9780-300X)
- Cristina Olgasi (ORCID: https://orcid.org/0000-0002-5738-213X)
- Lelia Wolf-van Bürck
- Laura Mar Fonseca (ORCID: https://orcid.org/0000-0001-7221-9413)
- Virginie Mathias
- Morgane Fouche
- Olivier Thaunat
- Jochen Seissler
- Francesco Campo
- Lorenzo Piemonti
Institutions
- Université Claude Bernard Lyon 1 (FR)
- École Normale Supérieure de Lyon (FR)
- University of Geneva (CH)
- Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- LMU Klinikum (DE)
- University Hospital of Geneva (CH)
- IRCCS Ospedale San Raffaele (IT)
- Centre International de Recherche en Infectiologie (FR)
- Geneva College (US)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Trends in biotechnology
- Published
- 2026-05-01
- DOI
- https://doi.org/10.1016/j.tibtech.2026.03.020
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Horizon 2020 Framework Programme
- JDRF