# Angiogenic hydrogel composites for microvascular integration of organoid grafts

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $335,494

## Abstract

PROJECT SUMMARY/ABSTRACT
 Graft integration of microvasculature is a critical next step for cell replacement strategies for type I
diabetics. The incorporation of host-connected microvasculature is essential for post-implantation graft survival
and over the longer-term impacts the kinetics of glucose response and systemic insulin delivery. Directing
angiogenesis into islet-containing synthetic hydrogels would guarantee host-connected microvasculature in the
graft, but control over angiogenesis remains limited. Our long-term goal is to understand how physical cues from
the cellular microenvironment impinge upon critical steps of angiogenesis and devise engineering methods to
incorporate these cues into translatable biomaterials. Angiogenesis involves a series of spatiotemporally
controlled cellular programs including endothelial tip cell activation and directed invasion, collective migration of
leading tip cells and ensuing stalk cells, and proliferation and lumenization of the multicellular strand. Our prior
work demonstrates a critical balance between tip cell migration and stalk cell proliferation during collective
migration required for forming functional microvessels, and that hydrogel degradability modulates the collectivity
of endothelial cell migration. Further, we have pioneered hydrogel composites containing physical cues in the
form of synthetic fibers that promote endothelial-to-mesenchymal transition and cause quiescent endothelial
cells to adopt invasive behavior suggestive of tip cells that lead angiogenic sprouts. Together, these observations
motivate our central hypothesis: modular control of hydrogel structure can drive the angiogenic formation of
microvasculature that supports the function of hPSC-derived pancreatic islet organoids. Using novel composite
hydrogels, organotypic tissue models, and assessments of vascular and islet function in vivo, we aim to
understand the microenvironmental regulation of endothelial cell decision-making during angiogenesis. In Aim
1, we will utilize hydrogel composites containing cell-adhesive guidance fibers to phenotypically transition
quiescent endothelial cells into invasive tip cells. In Aim 2, we will engineer hydrogel crosslinking and microscale
porosity to drive endothelial stalk cells proliferation and establish quantitative relationships between collective
migration of stalk cells, proliferative events, and microvessel lumenization. In Aim 3, we will use in vitro and in
vivo models to examine the impact of material-guided angiogenesis and resulting microvasculature on the
function of hydrogel grafts containing hPSC-derived islets. The proposed studies will 1) shed light on the
microenvironmental regulation of phenotypic transitions during angiogenesis and 2) identify biomaterial design
parameters that support functional angiogenesis. We anticipate the developed strategies to provide
microvascular support to engineered pancreatic islet grafts will have bearing on grafts containing other
...

## Key facts

- **NIH application ID:** 10813726
- **Project number:** 5R01EB030474-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Brendon M Baker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $335,494
- **Award type:** 5
- **Project period:** 2021-05-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10813726

## Citation

> US National Institutes of Health, RePORTER application 10813726, Angiogenic hydrogel composites for microvascular integration of organoid grafts (5R01EB030474-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10813726. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*