This project aims to develop a human derived Hemoglobin-Based Oxygen Carrier (HBOC) solution (Phase I) to be utilized in numerous ex-vivo applications (Phase II) where an oxygen delivery solution is required: 1) machine perfusion (MP) systems for organ and tissue preservation, 2) MP systems for the discovery of biomarkers, and 3) perfusate in human microchips for drug discovery. This is the first HBOC to be developed specifically for ex-vivo applications with the novel approach being an excipient that balances for ex-vivo fluid shifts. Furthermore, this new product will be developed within a streamlined, highly efficient commercial process that will allow a seamless transition to cost-effective Contract Manufacturing Organizations (CMO). VirTech Bio's HBOC and manufacturing process were conceived following successful proof-of-concept ex-vivo studies 1 with an HBOC (Hemopure®). Unfortunately, the company (OPK Biotech) went bankrupt in 2014. Hemopure had a complex and expensive manufacturing process 2,3 that precluded the use of any CMO. The main issues were related to bovine contamination, hydrogen gas toxicity and the need for expensive and specialized equipment. VirTech Bio's's new process developed for this SBIR Phase I proposal addresses all these concerns while creating a more cost-effective commercial production of this component. The initial source of human hemoglobin molecules will be expired human blood obtained through a process 4 already approved by regulatory bodies. The outdated human red blood cells will be `washed' via ultrafiltration, lysed by osmotic shock and purified by a three-step tangential flow filtration system to remove cellular impurities. Subsequently, polymerization will be with glutaraldehyde, followed by Schiff-base stabilization. The Specific aims include: 1) biophysical characterization to demonstrate similarity with the original HBOC, 2) stability testing of the molecular weight and storage parameters and 3) compatibility testing with machine perfusion (without the organs) for 12 hours at relevant conditions. This product once developed and validated will be coupled with a machine perfusion device in Phase II and utilized for liver preservation according to our previous experience. The new HBOC for utilization in organ preservation should have a significant positive impact in clinical transplantation. Effective organ oxygenation ex-vivo will enhance the current standards of organ preservation and increase the number of transplants 5. It should have additional positive downstream effects by decreasing the morbidity and the mortality on the transplant waiting list 6, improving post-operative outcomes and decreasing the length-of-stay 7. All these benefits should have a direct impact in the ability to decrease the overall costs in clinical transplantation 8. !
Public Health Relevance Statement: Project Narrative VirTech Bio is developing a human-derived oxygen transport solution designed for machine perfusion (MP) medical devices, and it will be utilized ex-vivo for organ and tissue preservation. Preliminary proof-of-concept pre-clinical experiments have been performed successfully with a similar bovine-derived product 1. Anticipated benefits include enhancement of organ and tissue viability, increased organ availability for transplants, and improved overall transplantation outcomes.
Project Terms: Address; Anions; base; Biological Preservation; biomarker discovery; biophysical properties; Biotechnology; Blood; Buffers; Carbon Dioxide; Cattle; Cell Survival; Clinical; Colloids; Complex; Contracts; cost; cost effective; Coupled; Cytolysis; design; Development; Devices; drug discovery; Equilibrium; Equipment; Erythrocytes; Excipients; Excision; experience; Filtration; Fluid Shifts; Formulation; Gases; Generations; Glutaral; Hemoglobin; Hour; Human; Hydrogen; improved; in vivo; Length of Stay; Light; liver preservation; manufacturing process; Measures; Medical Device; member; Membrane; Methods; microchip; Molecular Weight; Morbidity - disease rate; mortality; novel strategies; Organ; Organ Preservation; Organ Preservation Solutions; Organ Viability; Osmotic Pressure; Osmotic Shocks; Outcome; Oxygen; oxygen transport; Perfusion; Phase; polymerization; Postoperative Period; pre-clinical; pressure; Process; Production; Property; prototype; Reducing Agents; Reporting; Research; research study; Schiff Bases; Series; Small Business Innovation Research Grant; sodium borohydride; Source; stability testing; System; Temperature; Testing; Time; Tissue Viability; tissue/organ preservation; Tissues; TNFRSF5 gene; Toxic effect; Transfusion; Transplantation; Ultrafiltration; Universities; Variant; Waiting Lists; Wisconsin; Work
