# Perfusion decellularization and recellularization for the creation of a bioengineered transplantable liver

> **NIH NIH R44** · MIROMATRIX MEDICAL, INC. · 2020 · $867,941

## Abstract

ABSTRACT
Liver transplantation currently represents the only treatment for end stage liver disease (ESLD), the 8th most
frequent cause of death in the United States (US). Efforts to overcome the chronic shortage of transplantable
human livers include attempts at alternative organ procurement and replacement strategies. The most promising
approach to date that provides the appropriate matrix composition and supporting vascular structures has been
the development of perfusion decellularization, which enables the removal of cellular material for a native organ
while maintaining the native matrix, structure and vascular of the liver. Utilizing perfusion decellularization and
recellularization technology, several groups have demonstrated the ability to seed a variety of liver-specific cell
types into decellularized liver constructs, however reconstitution of the endothelial cell lining of the vascular
networks in these scaffolds has remained a significant challenge to the development of a therapeutic
bioengineered liver (BEL). Miromatrix Medical Inc. has recently reported revascularizing a clinically translatable
porcine-derived liver scaffold and demonstrated in vivo graft patency in a large animal model without sustained
administration of anticoagulant therapies. Solving the critical vascular constraint allows this Direct to Phase II
SBIR project to focus on production and testing of a fully functional BEL to address the chronic shortage of
transplantable livers and develop new therapeutic options to those with ESLD utilizing Miromatrix’ broad
proprietary perfusion decellularization and recellularization technology.
In Specific Aim #1, we will demonstrate recellularized liver graft function in an acute liver failure model. The
optimal media and seeding conditions for hepatocyte functionality will be selected (1.1). Equivalency of human
hepatocytes to porcine hepatocytes will be demonstrated (1.2), and vascular patency of endothelial and
hepatocyte recellularized livers will be confirmed in acute blood loops (1.3). Forty-eight hour functionality of this
liver graft will be demonstrated in pigs (1.4). In Specific Aim #2, we will optimize the seeding of cholangiocytes
into liver grafts recellularized with endothelial cells and hepatocytes and identify assays that will allow
assessment of cholangiocyte function after seeding to verify successful engraftment (2.1). We will then create
tri-culture grafts using only human cells and test for equivalency to the porcine+human grafts (2.2) and determine
whether addition of cholangiocytes to endothelial+hepatocyte liver grafts adversely affects graft patency (2.3).
Finally, in Specific Aim #3, we will demonstrate the BEL functionality in an orthotopic chronic liver failure model
by developing a transplant model and evaluating baseline data (3.1) and by demonstrating liver functionality for
fourteen days in a recovery model in pigs (3.2). Data generated will be used in a Pre-IND submission meeting
to define the ...

## Key facts

- **NIH application ID:** 10018893
- **Project number:** 5R44DK122894-02
- **Recipient organization:** MIROMATRIX MEDICAL, INC.
- **Principal Investigator:** Jeffrey James Ross
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $867,941
- **Award type:** 5
- **Project period:** 2019-09-17 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018893

## Citation

> US National Institutes of Health, RePORTER application 10018893, Perfusion decellularization and recellularization for the creation of a bioengineered transplantable liver (5R44DK122894-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10018893. Licensed CC0.

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