# Engineering a novel biomaterial for oxygen transport applications

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2021 · $664,429

## Abstract

Abstract
 Hemoglobin (Hb)-based oxygen (O2) carriers (HBOCs) are currently being developed as red blood cell
(RBC) substitutes for use in transfusion medicine. Despite significant commercial development, recent late
stage clinical results of polymerized hemoglobin (PolyHb) solutions (i.e. Hemopure (OPK Biotech,
Cambridge, MA), a glutaraldehyde polymerized bovine Hb; and PolyHeme (Northfield Laboratories Inc.,
Evanston, IL), a glutaraldehyde polymerized pyridoxylated human Hb) hamper further development. Both of
these commercial products elicit vasoconstriction at the microcirculatory level, and lead to the development of
systemic hypertension and oxidative tissue damage. These side-effects are hypothesized to occur either by a
nitric oxide (NO) scavenging or oxygen (O2) oversupply mechanism, and are both exacerbated by PolyHb
extravasation into the tissue space. In light of these 2 potential mechanisms, it is apparent that PolyHb size will
have a profound impact on the extent of vasoconstriction, systemic hypertension and oxidative tissue toxicity.
 However, commercial PolyHb products are complex mixtures with broad size distributions defined only by
the size cutoff of the ultrafiltration membranes used in their manufacture. Furthermore, these mixtures are
known to contain up to 1% of individual tetrameric Hb molecules and a significantly higher proportion of lower
molecular weight (MW) Hb oligomers (80% with MW < 500 kDa). Hence, the side-effects observed during
clinical/pre-clinical trials are attributed to a mixture of low MW Hb polymers with different sizes and points of
chemical modification, and not to any one, single PolyHb molecule. This precludes precise characterization of
how individual components of these complex PolyHb mixtures interact with the vasculature.
 An important advance would therefore be the ability to produce molecularly uniform, monodisperse, and
high MW PolyHb nanostructures. In this application, we hypothesize that the molecular diameter and
topology of recombinant PolyHb (rPolyHb) will regulate vasoactivity and oxidative injury to tissues. To
test our hypothesis we propose the following specific aims:
Specific Aim 1: Use orthogonal split splicing inteins to produce well-defined, monodisperse, high MW
rPolyHb nanostructures.
Specific Aim 2a: Analyze the role of endothelial function on the development of vasoactivity and oxidative
tissue injury to rPolyHbs of varying size.
Specific Aim 2b: Evaluate the pharmacokinetics of rPolyHbs in normal guinea pigs and HFSD guinea
pigs.
Specific Aim 3: Evaluate the ability of rPolyHbs to restore tissue oxygenation and optimize survival in
severe blood loss.
 The proposed work is both significant and innovative, since it seeks to develop safe and efficacious
rPolyHbs for use in transfusion medicine. In addition, state-of-the-art biophysical techniques and two unique
animal models will be used to understand rPolyHb physiological responses and determine the clinical potential
of thes...

## Key facts

- **NIH application ID:** 10145971
- **Project number:** 1R01HL156526-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Paul Werner Buehler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $664,429
- **Award type:** 1
- **Project period:** 2021-01-15 → 2025-01-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145971

## Citation

> US National Institutes of Health, RePORTER application 10145971, Engineering a novel biomaterial for oxygen transport applications (1R01HL156526-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10145971. Licensed CC0.

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