# Extracellular matrix regulation of differentiation via modulation of ILK:  application to 3D bioprinting of cardiac tissue

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $452,080

## Abstract

PROJECT SUMMARY
The primary objective of this proposal is to couple a) mechanistic insight relating differentiation outcomes to
ECM engagement via intracellular signaling events triggered at the focal adhesion (FA), with b) 3D printing of
ECM and ECM-associated proteins as a means to direct cell distribution with maturation and thereby enable
fabrication of thick, functional cardiac tissue. The proposal is significant as it has the potential to generate
replacement tissues and even heart grafts for individuals suffering from acute and chronic injury to the heart. It
is the first of its kind to address the conundrum of the apparent uniformity of the focal adhesion relative to the
myriad of different ECM/integrin combinations and the corresponding variety of cell behaviors that emerge from
ECM engagement. It does so by proposing that elements of the FA, namely integrin linked kinase (ILK) and
associated phosphatase, act as sensitive rheostats that can be co-opted to yield desired behavior. Here, the
desired behavior is cardiac differentiation, and the innovation is the utilization of optimized ECM formulations
as bioinks to create 3D cardiac tissue mimics (3DCTM) capable of directing cell distribution of multiple cell
types with differentiation. This concept is feasible as the Ogle laboratory has long-studied the biochemistry of
the ECM and stem cell behaviors associated with ECM engagement, and the McAlpine laboratory has focused
on 3D printing of functional materials for a range of applications, from biological to electronic and the merger of
these materials. These groups will also interface with expertise of the Kamp lab with respect to their recent
generation of induced cardiac progenitor cells (iCPCs) to populate the 3DCTM, the Provenzano lab to assist
with molecular mechanisms associated with FA formation, the Garry lab to assist with bioreactor
implementation, the Zhang lab to add cardiovascular physiology expertise, and the Talkachova lab to assist
with optical imaging to assess function of the 3DCTM and core facilities for mass spectrometry of ECM
components and gene editing tools for modulating ILK activity. Together, this expertise will be funneled toward
meeting the primary objective of the proposal via the following aims: 1) determine whether activation of
integrin-linked kinase (ILK) of focal adhesions or costameres couples integrin activation to β-catenin activation
via GSK3β to enable expression of genes associated with cardiomyocyte specification, 2) use 3D ECM-based
model systems to identify ECM formulations supportive of endothelial differentiation and assess ILK
dependence, and 3) use ECM-based 3D printing to modulate differentiation of cardiac cell types spatially in a
cardiac tissue mimic. The motivation for this concept was based on extensive literature search, and results
from our own experimentation; the approach was designed to insure that the interpretations of the results are
subject to minimal bias and the hypotheses po...

## Key facts

- **NIH application ID:** 10001078
- **Project number:** 5R01HL137204-04
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Michael McAlpine
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $452,080
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001078

## Citation

> US National Institutes of Health, RePORTER application 10001078, Extracellular matrix regulation of differentiation via modulation of ILK:  application to 3D bioprinting of cardiac tissue (5R01HL137204-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10001078. Licensed CC0.

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