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Developing a morphomics framework to optimize implant site-specific design parameters for islet macroencapsulation devices.

ABSTRACT: Delivering a clinically impactful cell number is a major design challenge for cell macroencapsulation devices for Type 1 diabetes. It is important to understand the transplant site anatomy to design a device that is practical and that can achieve a sufficient cell dose. We identify the posterior rectus sheath plane as a potential implant site as it is easily accessible, can facilitate longitudinal monitoring of transplants, and can provide nutritive support for cell survival. We have investigated this space using morphomics across a representative patient cohort (642 participants) and have analysed the data in terms of gender, age and BMI. We used a shape optimization process to maximize the volume and identified that elliptical devices achieve a clinically impactful cell dose while meeting device manufacture and delivery requirements. This morphomics framework has the potential to significantly influence the design of future macroencapsulation devices to better suit the needs of patients.

SUBMITTER: McDermott B

PROVIDER: S-EPMC8692035 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Developing a morphomics framework to optimize implant site-specific design parameters for islet macroencapsulation devices.

McDermott Barry B Robinson Scott S Holcombe Sven S Levey Ruth E RE Dockery Peter P Johnson Paul P Wang Stewart S Dolan Eimear B EB Duffy Garry P GP

Journal of the Royal Society, Interface 20211222 185

Delivering a clinically impactful cell number is a major design challenge for cell macroencapsulation devices for Type 1 diabetes. It is important to understand the transplant site anatomy to design a device that is practical and that can achieve a sufficient cell dose. We identify the posterior rectus sheath plane as a potential implant site as it is easily accessible, can facilitate longitudinal monitoring of transplants, and can provide nutritive support for cell survival. We have investigate ...[more]

PMID: 34932928

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Project description:Type 1 diabetic (T1D) patients are life-long dependent on insulin therapy to keep their blood glucose levels under control. An alternative cell-based therapy for exogenous insulin injections is clinical islet transplantation (CIT). Currently the widespread application of CIT is limited, due to risks associated with the life-long use of immunosuppressive drugs to prevent rejection of donor cells. An immunoprotective macroencapsulation device can protect allogeneic islet cells against the host immune system and allow exploring extrahepatic transplantation sites. We report on the characterization and creation of porous polyvinylidene fluoride (PVDF) membrane-based devices intended for islet and beta-cell transplantation. We hypothesize that by incorporating polyvinyl-pyrrolidone (PVP) into a PVDF solution the permeability of PVDF membranes for insulin and glucose can be improved by solvent-non solvent casting to create submicrometer porous films. We show that the use of water-soluble PVP, can significantly increase glucose diffusion through these membranes while still having the ability to block immune cells from migrating through these membranes. Human donor islets loaded into devices made from these thin PVDF/PVP membranes showed a 92 ± 4% viability after 8 days similar to their free-floating counterparts. The glucose responsiveness of human donor islets encapsulated inside PVDF/PVP membrane-based devices was significantly improved compared to islets seeded in devices made from PVDF membranes without PVP, with a stimulation index of 3.2 for PVDF/PVP devices and 1.3 for PVDF-alone devices at day 8. Our data show that by addition of PVP as pore forming agent during membrane fabrication at a specific ratio the diffusion characteristics can be tuned such that human islet function in these closed macrodevices, can be kept at the same level as non-encapsulated islets, while the membrane can still serve as a protective barrier preventing the entry of primary human macrophages and damaging beta cells.

Dataset Information

Developing a morphomics framework to optimize implant site-specific design parameters for islet macroencapsulation devices.

Publications

Developing a morphomics framework to optimize implant site-specific design parameters for islet macroencapsulation devices.

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