D25AC00320

HE WAKE FOREST INSTITUTE FOR REGENERATIVE MEDICINE (WFIRM) HAS OVER TWO DECADES OF EXPERIENCE USING A VARIETY OF 3D PRINTING MODALITIES TO DEVELOP IMPLANTABLE HUMAN TISSUE CONSTRUCTS. OVER TIME THE CELLULAR COMPOSITIONS AND IMPLANT DIMENSIONS RELEVANT TO CLINICAL APPLICATIONS HAVE INCREASED REQUIRING AN INTEGRATED VASCULAR SYSTEM THAT ALLOWS PERFUSION OF THE ENTIRE CONSTRUCT. THESE BIOPRINTED VASCULARIZED TISSUE CONSTRUCTS OPEN THE POSSIBILITY OF SUPPORTING A FUNCTIONAL MICROANATOMY THAT CAN PERFORM NUANCED ORGAN SPECIFIC FUNCTIONS. THE OVERALL STRATEGY WILL INCLUDE A PROTOCOL FOR COST EFFECTIVE CLINICAL MANUFACTURING OF A SUFFICIENT NUMBER OF AUTOLOGOUS RENAL CELLS FROM A SMALL SURGICAL SAMPLE OR TISSUE BIOPSY. THESE CELLS WILL BE COMBINED WITH A FUNCTIONALIZED HYDROGEL BIOINK THAT BOTH SUPPORTS THE LONG TERM VIABILITY OF THE EMBEDDED CELLS AND PROMOTES THE ACTIVATION OF ENDOGENOUS DEVELOPMENTAL PATHWAYS THAT GUIDE THE FORMATION OF A FUNCTIONAL CELLULAR MICROANATOMY. CUTTING EDGE MULTIPHYSICS MODELING WILL BE APPLIED TO NATIVE RENAL TISSUE TO ESTABLISH A BLUEPRINT THAT APPROXIMATES RENAL TISSUE ARCHITECTURE AT A RESOLUTION OF 50 UM. SOFTWARE WILL ALSO BE DEVELOPED TO TRANSLATE THIS BLUEPRINT INTO A PRINTABLE CODE THAT WILL GUIDE THE RAPID PRODUCTION OF RUDIMENTARY RENAL TISSUE. THESE CONSTRUCTS WILL BE FURTHER ENHANCED THROUGH MATURATION IN A SPECIALIZED PERFUSION BIOREACTOR WITH AN INTEGRATED SENSOR SUITE THAT MONITORS TISSUE FUNCTION. STRATEGIES WILL ALSO BE DEVELOPED USING SMALL AND LARGE PRECLINICAL ANIMAL MODELS TO PROMOTE FURTHER REMODELING OF BIOPRINTED RENAL TISSUE FOLLOWING IMPLANTATION. THE OVERARCHING GOAL IS THE PRODUCTION OF BIOPRINTED VASCULARIZED AUTOLOGOUS RENAL TISSUE TO AUGMENT RENAL FUNCTION IN PATIENTS SUFFERING FROM KIDNEY DISEASE. THIS TISSUE THERAPY WILL BE QUALIFIED USING IND ENABLING PRECLINICAL ANIMALS IN PARALLEL WITH A COMMERCIALIZATION PLAN TO MAKE THIS A COST EFFICIENT SOLUTION TO THE NATIONS GROWING DONOR ORGAN SHORTAGE.

Wake Forest University Health Sciences

SIGNIFICANT HEALTH IMPACT FOR THE FUTUREOF ORGAN TRANSPLANTATION AND PAVE THE WAY FOR THE NECESSARY NEXT STEPS IN SCALING TISSUE AND ORGANENGINEERING.

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

Interior Business Center (IBC) [DOI]

North Carolina United States

State-Wide

D-AQD-FA-25-013