# Conformal islet encapsulation for transplantation at vascularized sites to allow physiological insulin secretion

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2021 · $464,757

## Abstract

Islet transplantation (ITX) is experiencing increasing clinical success, but its applicability for type 1 diabetes
(T1D) is currently limited by the need for lifelong chronic immunosuppression (IS) and the high number of islets
from deceased organ donors needed to reverse T1D. Islet encapsulation is a possibility to reduce or eliminate
chronic IS, but, so far, traditional 1000 µm fixed-diameter capsules implanted in the peritoneal cavity failed to
provide sufficiently effective and long-lasting outcomes. Most likely, this is because large and avascular
capsules limit nutrient transport and delay glucose-stimulated insulin release (GSIR) causing loss of graft
functionality. Recently, we developed an encapsulation technology that allows ‘wrapping’ each individual islet
with a uniformly thin (»15 µm) layer of biomaterial, generating capsules that ‘conform’ to the size and shape of
the islet rather than enclosing them in fixed-diameter traditional capsules. By reducing the diffusion distance
10-fold, this conformal coating (CC) allows increased nutrient transport. By reducing the overall graft volume
more than 100-fold (from ~500 to ~3 mL), CC also makes possible transplantation in well vascularized
confined sites, including pre-vascularized devices, and is no longer limited to the intraperitoneal cavity, further
maximizing nutrient transport. Contrary to islets in traditional microcapsules, CC islets display no delay in
GSIR, and our computational model predicts that CC grafts placed in confined sites will provide physiological
insulin release (GSIR) after revascularization. We were able to confirm long-term euglycemia after
transplantation of fully MHC-mismatched CC grafts in diabetic mice without immunosuppression. To address
another main shortcoming of current ITX protocols, we recently found that our CC platform is also suitable for
use with essentially unlimited insulin-secreting cell sources derived from stem cells (SC-b). Accordingly, we
hypothesize that our unique CC technology can allow long-term function of primary islets and SC-b cell grafts
without the need for immunosuppression using clinically applicable coating hydrogels (aim 1). Further, we
hypothesize that by using innovative nanomaterials, we can provide local immunomodulation and higher
oxygen tension at the CC graft site in the immediate post-transplant period minimizing the number of cells
needed to reverse T1D and maximizing long-term graft function (aim 2). The work in preclinical mouse models
proposed here is needed before we can test our base and nanomaterial-refined CC platform in primates and
then in humans.

## Key facts

- **NIH application ID:** 10062501
- **Project number:** 5R01DK109929-04
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Alice Tomei
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $464,757
- **Award type:** 5
- **Project period:** 2017-12-11 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10062501

## Citation

> US National Institutes of Health, RePORTER application 10062501, Conformal islet encapsulation for transplantation at vascularized sites to allow physiological insulin secretion (5R01DK109929-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10062501. Licensed CC0.

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