# Developing a Novel Vascularized Bone Microdevice for Investigating the Post-Stroke Bone Microenvironment

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $38,029

## Abstract

PROJECT SUMMARY
Ischemic stroke is a serious condition affecting nearly 800,000 people in the United States annually and is a
leading cause of long-term disability. Although stroke survivors commonly experience accelerated bone loss and
higher fracture risk compared to typically aging adults, the underlying causes remain poorly understood and
cannot be explained solely by bedrest. Inflammatory cytokines are present in serum post-stroke, but whether
cytokine dysregulation is a driving factor for altered bone remodeling following stroke – as seen in inflammatory-
related bone loss in other conditions like arthritis – is unknown. Our primary hypothesis is that the inflammatory
environment seen post-stroke stimulates a pro-inflammatory response in bone vasculature that acts to suppress
osteoblast activity and drive an increase in secreted proteins to activate bone resorptive programs. Microdevices
and “organ-on-chip” constructs are effective 3D in vitro platforms for mechanistically probing different cell-cell
interactions in controlled microenvironments. Such microdevices have been used successfully to examine the
response of different niches within bone to pharmaceuticals, radiation, and genetic disorders, but they have not
yet been used to examine mineralized bone and vascular interactions. The overall goal of this project is to expand
understanding of underlying factors contributing to stroke-related bone loss, specifically inflammatory factors, by
developing and implementing a bone-vascular microdevice platform that mimics the mineralized bone
microenvironment. Aim 1 will determine optimal manufacturing conditions for producing a mineralized
extracellular matrix (ECM) scaffold for osteoblast support in the microdevice. Aim 2 will develop the novel bone-
vascular microdevice platform and investigate osteoblast-endothelial cell interactions under homeostatic
conditions. Aim 3 will determine the effects of inflammatory cytokines interleukin-6, interleukin-1β, and interferon-
γ on osteoblast-endothelial paracrine signaling using the microdevice platform. We will accomplish these aims
by leveraging traditional ECM scaffold fabrication techniques with passive mineral deposition, computational fluid
dynamics modeling of fluidic shear and nutrient transport, and biological assays of osteoblast activity and
vascular barrier function. This work will create a new in vitro platform that enables mechanistic probing of
complex bone-vascular interactions and advance understanding of inflammatory regulation of bone loss post-
stroke, thereby providing a framework that may inform better treatment strategies to mitigate stroke-related bone
fragility.

## Key facts

- **NIH application ID:** 10463277
- **Project number:** 1F31AR079897-01A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Sandra Jeanne Stangeland-Molo
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $38,029
- **Award type:** 1
- **Project period:** 2022-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463277

## Citation

> US National Institutes of Health, RePORTER application 10463277, Developing a Novel Vascularized Bone Microdevice for Investigating the Post-Stroke Bone Microenvironment (1F31AR079897-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10463277. Licensed CC0.

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