# Utilizing biodegradable porous silicon membranes as a novel design for lung-on-achip microfluidic devices to investigate extracellular matrix interactions.

> **NIH NIH SC3** · FORT LEWIS COLLEGE · 2022 · $20,755

## Abstract

Project Summary
Identifying the cellular pathways that promote disease or which prospective therapies are effective relies upon
appropriate mammalian models. Therefore, there is an urgent need for advanced human model systems that
can accurately reproduce human anatomy and physiology to help predict human disease progression and as-
sess potential treatment options. The long-term goal is to utilize a novel in vitro lung-on-a-chip (LOAC) microflu-
idic device to predict how xenobiotics lead to inflammatory, fibrotic and immunomodulatory pulmonary diseases
in humans. The overall objective is to create the first fully organic LOAC that is structurally supported by a cell-
derived extracellular matrix (ECM) and includes innate immune cells to simulate organ-level functionality. The
rationale for the proposed research is to employ the unique properties of porous silicon (PSi) not previously
explored to revolutionize the field of material science in the fabrication of microfluidic platforms that incorporates
dynamic ECM changes. Guided by strong preliminary data, the overall objective will be accomplished by pursing
the following three specific aims: 1) Identify the optimal parameters and cellular mechanisms to dissolve ultrathin
porous silicon during long-term culture; 2) Determine the extent to which co-cultured cells within the LOAC se-
crete and create their own ECM; and 3) Develop a multicellular alveolar structure to activate immune cells leading
to extravasation and ECM remodeling using an in vitro model of pulmonary hypertension. Under the first aim,
the working hypothesis based on preliminary data is that human macrophages (MACs) are essential to modify
and dissolve PSi. Dissolution rates of PSi will be quantified through scanning electron microscopy (SEM) and
surface analysis will be completed by atomic force microscopy (AFM) to reproducibly create flexible, structurally
intact membranes. Under the second aim, the working hypothesis is that endothelial cells (ECs) will express and
secrete cell-derived ECM proteins. Secretion of de novo synthesized ECM components will be quantified through
RT-PCR, spinning disk and light sheet microscopy, LC/MS analysis and AFM. The third aim based on preliminary
data indicate epithelial cells (EPCs), ECs and MACs can be successfully co-cultured and are viable during long-
term culture on PSi membranes. The working hypothesis is in the presence of hypoxic conditions, MACs will
become activated and release soluble mediators leading to apoptosis of ECs and increased ECM remodeling
that will be quantified through confocal IF microscopy and live cell imaging. The proposed research is innovative,
in our opinion, because it represents a substantive departure from the status quo by utilizing the unique charac-
teristics of PSi, which is a biocompatible and biodegradable material. In addition, utilizing PSi provides the ca-
pability to create a cell specific ECM that will release biochemical cues including growth fact...

## Key facts

- **NIH application ID:** 10553441
- **Project number:** 3SC3GM141838-02S1
- **Recipient organization:** FORT LEWIS COLLEGE
- **Principal Investigator:** David James Blake
- **Activity code:** SC3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $20,755
- **Award type:** 3
- **Project period:** 2021-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10553441

## Citation

> US National Institutes of Health, RePORTER application 10553441, Utilizing biodegradable porous silicon membranes as a novel design for lung-on-achip microfluidic devices to investigate extracellular matrix interactions. (3SC3GM141838-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10553441. Licensed CC0.

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