D25AC00239

THE OBJECTIVE OF THIS PROPOSAL IS TO DEVELOP A VASCULARIZED IMMUNOCOMPETENT TISSUE AS AN ALTERNATIVE LIVER (VITAL). THE TRANSFORMATIVE VITAL LIVER WILL INCLUDE SUTURABLE BLOOD VESSELS TO ENABLE ORTHOTOPIC TRANSPLANTATION IN PATIENTS. IN TECHNICAL AREA 1 (TA1) WE WILL DEVELOP PROTOCOLS TO GENERATE LIVER CELLS FROM BLOOD SAMPLES AND LIVER BIOPSY OF PATIENTS FROM VARIOUS ETHNICITIES AND GENDERS TO ENSURE IMMUNE COMPETENCY AND DEMONSTRATE THEIR LIVER SPECIFIC FUNCTIONS. IN TA2 AT THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER (UTSW) WE WILL DEVELOP GLP CELL MANUFACTURING PROCESSES TO SCALE UP THE PRODUCTION OF LIVER CELLS IN A COST EFFECTIVE MANNER USING PERFUSION BIOREACTOR TECHNOLOGY. IN PARTNERSHIP WITH THE UNIVERSITY OF CALIFORNIA DAVIS (UC DAVIS) GOOD MANUFACTURING PRACTICES (GMP) FACILITY WE WILL DEMONSTRATE GMP COMPLIANT CELL MANUFACTURING WITH VALIDATED LIVER SPECIFIC FUNCTIONS UTILIZING THE SAME PERFUSION BIOREACTOR TECHNOLOGY OPTIMIZED AT UTSW. IN TA 3 WE WILL USE OUR PROPRIETARY BIO PRINTABLE HYDROGELS (BIOINKS) THAT RECAPITULATE THE UNIQUE LIVER MICROENVIRONMENT FOR CELL GROWTH CREATE SUTURABLE VASCULATURE WITH PROVEN BLOOD COMPATIBILITY WITH RESISTANCE TO BLOOD CLOTTING AND PROVIDE STRONG BIO ADHESION TO ACHIEVE A COHESIVE BIOFABRICATED ORGAN CRITICAL FOR MAINTAINING ORGAN INTEGRITY FOLLOWING TRANSPLANTATION. IN COLLABORATION WITH PENN STATE WE WILL EVALUATE THREE DISTINCT BIOFABRICATION STRATEGIES TO DEVELOP THE VITAL LIVER GUIDED BY LIVER ARCHITECTURE MODELS GENERATED THROUGH MULTI PHYSICS SIMULATIONS. OUR GOAL IS TO IDENTIFY THE MOST VIABLE APPROACH FOR SCALING THE VITAL LIVER AND DEMONSTRATE ITS FULL FUNCTIONALITY AND SAFETY IN BOTH MICE AND PIGS. ADDITIONALLY WE WILL DEVELOP A PARAMETRIC ALGORITHM TO GENERATE A BRANCHED ORGAN VASCULAR TREE WHICH WILL BE PACKAGED INTO AN EASY TO USE OPEN SOURCE INTERFACE.

The University Of Texas Southwestern Medical Center

93.384 - ADVANCED RESEARCH PROJECTS AGENCY for HEALTH (ARPA-H)

Interior Business Center (IBC) [DOI]

Multi-State United States

Multi-State

D-AQD-FA-25-013