# In vitro source of human extracellular matrix to support tissue repair and regeneration

> **NIH NIH R03** · BROWN UNIVERSITY · 2020 · $81,250

## Abstract

Program Director/Principal Investigator (Last, First, Middle): Ip, Blanche C.
PROJECT SUMMARY:
Ideally, patients with tissue and organ failure would be treated using biologics of human origin, but there exists
an acute shortage of transplantable organs and available tissue repair materials. Injectable biologically complex
hydrogels, including extracellular matrix (ECM) formulated from extracts of healthy tissues, are emerging as a
promising new treatment. ECM can be extract from non-human tissues, But, the animals ECM is composed of
proteins foreign to humans that limits their effectiveness or even causes further tissue damage. Healthy human
hearts are not a source of ECM because they are too valuable for transplantation and cadaver hearts are
unsuitable. An intriguing alternative could be ECM secreted by human cells cultured in vitro. However, the
biochemical composition and physical properties of cell-secreted ECM are highly sensitive to culture conditions,
of which this basic science is poorly understood. Therefore, cells cultured on scaffolds (of natural or synthetic
polymers) or non-physiological stiff plastic surfaces with reduced cell densities, decreased cell-cell contact and
altered cell-matrix adhesions may generate ECM with differing composition and therapeutic efficacy. Needed is
a new scaffold-free method of generating human ECM to support tissue repair and regeneration.
Our long-term goal is to develop therapeutic human ECM from lab-grown three-dimensional (3D) human tissues
from human cell lines that are biofabricated without the use of scaffolds or non-physiological stiff surfaces. Our
central hypothesis is that the human cardiac ECM from our lab-grown 3D scaffold-free tissues will exhibit
overall composition and mechanics more consistent with ECM from native human cardiac tissue relative to ECM
from porcine cardiac tissue and 3D cardiac cell-sheets. PI: Ip and Collaborator: Morgan have preliminary data
and extensive complementary expertise for the proposed study to accomplish study goals which require 1) a
robust technological platform that can generate stable 3D scaffold-free cardiac tissue, where cells do not interact
with polymeric scaffolds or tissue culture plastic, 2) an optimized decellularization protocol to generate
decellularized ECM that is free of cells and DNA and retains the native protein composition and structure, 3)
thorough evaluation in the quality and injectability of ECM generated from our 3D scaffold-free tissue and contrast
the results with ECM from 3D cell sheet grown on stiff plastic surface, and from native human and porcine cardiac
tissue. In this R03, we will utilize our patented micro-mold technology to generate stable 3D scaffold-free human
cardiac tissue with human cardiac fibroblasts, cardiomyocytes and cardiac microvascular endothelial cells and
evaluate three decellularized protocols to generate optimal quality decellularized ECM in Aim 1. We will then
develop, optimize and execute three compleme...

## Key facts

- **NIH application ID:** 9929626
- **Project number:** 5R03EB028056-02
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Blanche C IP
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $81,250
- **Award type:** 5
- **Project period:** 2019-05-15 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9929626

## Citation

> US National Institutes of Health, RePORTER application 9929626, In vitro source of human extracellular matrix to support tissue repair and regeneration (5R03EB028056-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9929626. Licensed CC0.

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