Changes in local tissue microenvironment in response to subcutaneous long-acting delivery of tenofovir alafenamide in rats and non-human primates

Pons‐Faudoa, Fernanda P.; Trani, Nicola Di; Capuani, Simone; Hernandez, Nathanael; Wood, A.M.; Nehete, Pramod N.; Niles, Jean A.; Shelton, Kathryn A.; Kezar, Sarah; Bushman, Lane R.; Chua, Corrine Ying Xuan; Ittmann, Michael; Anderson, Peter L.; Nehete, Pramod N.; Arduino, Roberto C.; Nichols, Joan E.; Grattoni, Alessandro

doi:10.1016/j.jconrel.2023.04.037

Cited by 3 publications

(2 citation statements)

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“…The composite laminates provoked mild fibrotic reactions in both IP and EFP sites in mice, which might facilitate the long-term efficacy of the encapsulation system. Further analysis and comparison of the cellular composition in the FBR capsules between materials of different mechanical strengths would provide more detailed information on the relation between mechanical properties and FBR. , The thickness of 3-layered laminates was ∼1 mm, which was thinner than most of the macroencapsulation devices. , Despite the complex architecture, the devices kept a 2-dimensional configuration, which could provide a large surface-to-volume ratio for efficient mass transfer. The space between the hydrogel and PES membranes allowed the infiltration of nutrients and cells into the semiopen structure of the laminates, which might increase the mass transfer compared to the closed structure of conventional diffusion chambers.…”

Section: Discussionmentioning

confidence: 99%

“…Further analysis and comparison of the cellular composition in the FBR capsules between materials of different mechanical strengths would provide more detailed information on the relation between mechanical properties and FBR. 36,37 The thickness of 3-layered laminates was ∼1 mm, which was thinner than most of the macroencapsulation devices. 15,38 Despite the complex architecture, the devices kept a 2dimensional configuration, which could provide a large surfaceto-volume ratio for efficient mass transfer.…”

Section: Discussionmentioning

confidence: 99%

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Hydrogel-Composited Laminate for Islet Immune-Isolation to Treat Type 1 Diabetes

Wang,

Wang

et al. 2024

ACS Appl. Mater. Interfaces

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Challenges remain to be solved for the clinical translation of β-cell encapsulation technology in the treatment of type 1 diabetes (T1D). Successful delivery of β cells urgently needs the development of an encapsulation device with a thin dimension and rapid mass transport that offers stable immune isolation and complete retrieval. In this study, we focus on a laminate in which an islet-embedding alginate hydrogel layer (Alg) is sandwiched between two polymer layers (polyether sulfone, PES). Mechanical support by the PES layer protects the alginate from disintegrating after implantation and allows complete retrieval. The multilayered device has a thin membrane configuration (∼1 mm), and the edge of the laminate and the gaps between Alg and PES offer a semiopen structure that could be more permeable to molecules compared with the closed pocket of conventional macroencapsulation. Islets are suspended in the alginate solution and then encapsulated in the hydrogel layer in the middle of the laminate after gelation. Encapsulating syngeneic or xenogeneic islets in the laminate device corrected chemically induced T1D in mice for over 90 days in both the intraperitoneal space and the epididymal fat pad. The multilayered membrane system may therefore provide a translatable solution in β cell-transplantation therapy in T1D.

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