Novel Artificial Erythrocyte for In-Field Resuscitation of Hemorrhagic Shock

Abstract

The first ErythroMer prototype (EM-V1) was structurally stable and toroidal, with diameter ~ 1/50th that of RBCs and amenable to lyophilization and rapid reconstitution. In addition, EM p50 (with novel pseudo-Bohr effect), NO sequestration and vaso-activity were equivalent to RBCs establishing POC for the bio-inspired design. We also developed a rabbit hemorrhagic shock resuscitation model (40 BV removal; outcomes: mean arterial pressure, lactic acidosis and liver pO2); in this model, EM was non-inferior to shed blood and superior to 5 Albumin. To further optimize biocompatibility, circulation time, and Hb payload density and retention, we developed EM-V2. In prior progress reports, we included data on V2 biophysical and functional characterization, which recapitulates RBC physiology similarly (to V1). PK testing with EM-V2 revealed extended elimination t1/2=4.5hrs in rabbits (n=4). In rabbit acute hemorrhagic shock resuscitation studies, EMV2 also demonstrated superiority to 5 Albumin and non-inferiority to shed blood (N=6/group). Of note, just prior to the end of project Y2, Dr. Doctor was recruited from Washington University (WUSM) to the University of Maryland (UMB), to serve as founding director for the Center for Blood Oxygen Transport and Hemostasis (CBOTH), a major resource that will accelerate EM development. Related to this transition, there were changes with other key personnel, which are detailed below, including transition of KaloCyte from the St Louis Cortex District to the Baltimore Biopark (KC lab is now embedded in CBOTH, facilitating collaboration). Resulting from these changes, the timing of contract transition from WUSM to UMB, and from COVID19 related lab shutdowns, the only project work in Y3, was performed by KaloCyte; information is provided in detail below. As such, an NCE was requested and approved, enabling the team to resume progress (NCE-Y4) towards completing project goals; a time-adjusted SOW is included in this report.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2020
Accession Number
AD1133097

Entities

People

  • Allan Doctor

Organizations

  • University of Maryland School of Medicine

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Acid-Base Imbalance
  • Biomedical Research
  • Blood
  • Blood Cells
  • Blood Substitutes
  • Chemical Synthesis
  • Chemistry
  • Contracts
  • Covid-19
  • Department Of Defense
  • Drying
  • Electronic Mail
  • Freeze Drying
  • Health Services
  • Hemorrhagic Shock
  • Hemostasis
  • Medical Personnel
  • Patient Care
  • Payload
  • Resuscitation
  • Schools
  • Therapy
  • Transitions

Readers

  • Technical Research and Report Writing.
  • Toxicology/Environmental Toxicology
  • Trauma Surgery or Emergency Medicine.

Technology Areas

  • Biotechnology