# Fiber-reinforced hydrogels to guide the formation and integration of engineered microvasculature

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $34,253

## Abstract

PROJECT SUMMARY
Tissue engineering and regenerative medicine is a rapidly growing field striving to develop biological constructs
that restore, maintain, or improve the function of a tissue or organ. While the past few decades have reported
success in relatively thin non-vascularized tissues, the development of large and complex tissues requires
adequate blood supply throughout the construct upon implantation. Specifically, rapid integration (~1 day) of
engineered vasculature is essential to graft survival by providing nutrients and oxygen to all cells within the living
construct. While many have reported successful assembly of vascular networks in vitro, vessel maturation and
rapid anastomosis to host vasculature post-implantation remain significant challenges. Thus, the long-term goal
of this work is to establish a prevascularized biomaterial that supports rapid host integration and subsequent
perfusion. Towards this goal, the overall objective of this proposal is to understand the role of ECM physical
properties, specifically fibrous microstructure, in 1) regulating the self-assembly of endothelial cells (ECs) into a
mature vascular network and 2) promoting host cell invasion and integration upon implantation. Our central
hypothesis is that the incorporation of fibrous structure into synthetic hydrogels will increase the rate of assembly
and maturation of microvessels as well as increase host cell invasion upon implantation, both of which will lead
to faster anastomosis and perfusion in vivo. Our preliminary data utilizing electrospun fibrous matrices supports
this hypothesis, indicating that deformable fibrous microenvironments promote mechanical communication
between ECs that underlies the formation and maturation of multicellular structures. In the first aim we will utilize
3D fiber reinforced dextran vinyl sulfone (DexVS) synthetic hydrogels to investigate the role of mechanical
communication in the formation and maturation of functional microvascular networks. We will first determine
optimal physical matrix conditions (e.g. bulk stiffness, fiber density) that support long range force transmission
and mechanical communication by quantifying cell force mediated 3D matrix deformations. Additionally, we will
utilize these results to intelligently design fibrous DexVS hydrogels that promote rapid formation of mature,
functional vascular networks. Maturation of these networks will be analyzed by quantifying network morphology,
strength of cell-cell junctions, and anastomoses and perfusion within a microfluidic device. In Aim 2, we will
determine the ability of prevascularized fibrous DexVS matrices to support rapid host engraftment in a SCID-
mouse subcutaneous model. Implants will be dissected from mice at various time points within the first week to
quantify perfusion rate of implanted vessels as well as host cell invasion into the graft. The contribution of this
work is expected to be a novel synthetic fibrous biomaterial that supports rapid...

## Key facts

- **NIH application ID:** 9989346
- **Project number:** 1F31HL152501-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Christopher Durbin Davidson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $34,253
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989346

## Citation

> US National Institutes of Health, RePORTER application 9989346, Fiber-reinforced hydrogels to guide the formation and integration of engineered microvasculature (1F31HL152501-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9989346. Licensed CC0.

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