# Synthesis and High-Throughput In Vivo Characterization of Alginate Encapsulation Materials for Long-Term Islet

> **NIH NIH R01** · RICE UNIVERSITY · 2021 · $12,777

## Abstract

Diabetes remains a global epidemic afflicting more than 300 million people worldwide, with incidence only
expected to rise. Despite decades of research the current standard of care for those suffering from type I
diabetes (TID) remains a rigorous regimen of blood glucose monitoring together with daily administrations of
exogenous insulin and diabetic diet, these individuals still are challenged with untoward side effects due to
complications of the disease in part the result of daily compliance issues. Islet transplantation has tremendous
potential, but serious technological limitations remain. The lack of suitable biomaterials used for cell
encapsulation is one of the key obstacles to clinical application. Cell encapsulation materials used to date are
immunogenic, and lead to tissue capsule formation and cell graft failure.
To address this challenge, here we propose the synthesis of 7000 candidate immune modulatory alginate-
based hydrogel capsule formulations for cell encapsulation and a high-throughput in vivo method for
identification of novel materials which can enable long-term protection and viability of transplanted donor
pancreatic islet cells. A first-generation screen of 774 alginate formulations guides our design of this proposed
second generation 7000 analogue structures. To enable increased throughput of screening, we propose to
implant mixtures of different materials in the same implantation site. To pair the material identity with the
observed material function, we are developing a next-generation sequencing (NGS) assay to determine
material identity via a single nucleotide polymorphism (SNP) genotype of co-encapsulated HuVEC cells.
Preliminary results using a 84-plex SNP NGS panel on 23 volunteers indicate high confidence genomic
identification using limited NGS reads. Thus, a typical implantation of 200 alginate beads (1.5mm diameter)
allows the simultaneous evaluation of 20 different implanted materials, with still sufficient independent beads
per material to allow statistical analysis.
In the course of this research project, the PI will first synthesize the new analogue library compounds.
Subsequently, the PI will screen these materials in vivo using a xenogeneic transplantation of islets/HuVEC
mixtures into a profibrotic C57BL/6 model rodents, that enables us to simultaneously screen up to 20-fold more
distinct materials formulations in a single rodent. Next, the PI will examine the ability of leads (5-10)
formulations to protect transplanted islet and restore normoglycemia in a T1D rodent model for up to 100 days.
Finally lead formulations will be further vetted in healthy non-human primate studies. We anticipate that upon
completion of this project, lead alginate materials for encapsulating islet cells will be identified that succeed in
two different animal models (C57BL/6 mouse and macaque monkeys) and will be ready for pre-clinical tests
under GLP/GMP conditions in preparation for an FDA IND submission.

## Key facts

- **NIH application ID:** 10417320
- **Project number:** 3R01DK120459-04S1
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** Omid Veiseh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $12,777
- **Award type:** 3
- **Project period:** 2018-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10417320

## Citation

> US National Institutes of Health, RePORTER application 10417320, Synthesis and High-Throughput In Vivo Characterization of Alginate Encapsulation Materials for Long-Term Islet (3R01DK120459-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10417320. Licensed CC0.

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