# Isochoric Pressure Based Preservation of Cells, Tissues and Organs

> **NIH NIH R44** · SYLVATICA BIOTECH, INC. · 2021 · $890,768

## Abstract

PROJECT SUMMARY/ ABSTRACT
There is wide recognition within the transplant and broader biomedical communities, as well as government
funding agencies, that extended and improved preservation of biological materials is needed for a huge range of
endeavors in biomedicine, medical research and drug discovery, organ and tissue transplantation, cell-based
therapies, fertility and regenerative medicine, emergency preparedness, and trauma care. The current standard of
preservation for organs and vascular composite allografts (VCAs) consists of few hours of hypothermic static
storage in UW solution on ice. This contributes to organ/VCA shortage and increased discard rates, exacerbates
ischemic injury and graft rejection due to suboptimal donor-recipient matching, and diminishes the quality of life
for transplant recipients. To address these challenges, we have pioneered a novel thermodynamic
approach to biopreservation, based on a stable equilibrium state and isochoric (constant volume)
condition, at high subzero (-5°C to -20 °C) temperatures, that will allow effective preservation of organs
and VCAs, with a 20x-28x increase in storage duration over the current clinical practice (<6-12h of hypothermic
storage) while avoiding cellular injury and other challenges created by storage at deep cryogenic temperatures.
Importantly, we will build on the successful demonstration of feasibility in Phase I and the results that Sylvatica
and UC Berkeley have collaboratively demonstrated with regard to high subzero isochoric preservation: (1)
biocompatible thermodynamic pressure profiles for preservation cocktails that support human cell survival in isochoric
systems with viabilities above 75%, (2) successful initial scale-up of isochoric preservation to whole rat hearts and skin
at unprecedented temperatures (-8°C, -10°C), and (3) isochoric preservation of fish muscle and an entire organism (the
research model C. elegans). Therefore, the objective of this Phase II proposal is to demonstrate, using animal and
human models of VCA representative tissues and limb preservation, prolonged cryopreservation of VCAs for
5-7 days and weeks, or longer, with good functional outcome post storage and recovery. Across five specific aims,
we will first employ skin and vascular models of VCAs for cryostasis cocktail and protocol optimization, with the central
goal of enabling high subzero isochoric preservation while actively suppressing metabolism and enhancing
stress tolerance. An isochoric preservation platform (chamber, pressure/temperature sensors) based on the
successful system used in Phase I will be designed and built to support cryostasis protocols validation using
clinical size human skin and blood vessels, then a model of rat forelimb preservation and assessment through
pseudo transplantation, and then by orthotopic allotransplantation with comprehensive characterization of upper
extremity functional and behavioral recovery. The results from the animal preservation/transpla...

## Key facts

- **NIH application ID:** 10142363
- **Project number:** 5R44AI145782-04
- **Recipient organization:** SYLVATICA BIOTECH, INC.
- **Principal Investigator:** Gerald Brandacher
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $890,768
- **Award type:** 5
- **Project period:** 2016-08-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142363

## Citation

> US National Institutes of Health, RePORTER application 10142363, Isochoric Pressure Based Preservation of Cells, Tissues and Organs (5R44AI145782-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10142363. Licensed CC0.

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