The PRINT program aims to transform organ biofabrication by leveraging recent advances in 3D bioprinting, cell manufacturing, biomaterials, modeling, and tissue engineering. The platform will use patient-matched organ biofabrication to restore normal human organ function for the kidney, heart, or liver. While over 45,000 transplants are performed in the US annually, there are still more than 120,000 patients remaining on wait lists who experience 10% mortality while waiting for donated organs. Current efforts at biofabrication have been limited by their ability to produce a sufficient number of cells and print and maintain complex tissues ready for transplantation. Additionally, no existing approach has been able to deliver a fully patient immunocompetent solution. The PRINT program will assemble the necessary tools to facilitate production from a human cell source to a patient matched biofabricated organ to restore at least 40% normal organ function as demonstrated in a large animal model. These tools include: 1) robust methods for cell source differentiation and/or expansion of immunocompetent organ specific cell types, 2) bioreactors and cell biobanks to reach organ level cell number, 3) a library of bioinks capable of recapitulating each unique microenvironment and cellular niche, 4) software to both model complex tissue organization as well as control advanced printing systems, 5) hardware for rapid high resolution precision bioprinting controllers and nozzles, and 6) perfusion chamber enabling effective tissue maturation and transportation to the patient bedside prior to transplantation, among others, as necessary. Successful delivery of this approach will have significant health impact for the future of organ transplantation and pave the way for the necessary next steps in scaling tissue and organ engineering.
All responsible sources capable of satisfying the Government’s needs may submit a proposal. Proposers may only submit one (1) proposal as the prime proposer and a sub-proposer on one (1) other, or subproposer on two (2) proposals. Proposers may not participate in research and development activities for more than two (2) proposals. Proposers can provide an agent/device at cost for more than two (2) teams, as long as there are no development efforts for any teams past two (2).
Solution Summary Due Date and Time: May 28, 2024, 9:00 AM ET
Proposals will be by invitation only. Proposal Due Date and Time: July 8, 2024, 5:00 PM ET
- Technical Area 1 (TA1): Generation of all necessary organ cell types (Phase I): Identify best in case cell source, either autologous or allogeneic (without any immunogenicity from tissue biopsy) induced Pluripotent Stem Cells (iPSCs). Criteria for selecting a cell source should be cost effective, multipotent, and immunocompetent. Assessment may include the verification of morphology using microscopy, multipotency, Fluorescence-activated cell sorting (FACS), or Quantitative polymerase chain reaction (qPCR), but is not limited to these techniques. The ultimate goal for this technical area will be to demonstrate cell type specific organ function in vitro.
- Technical Area 2 (TA2): Large scale manufacturing of organ cell types (Phase I & II): Based on the data from TA1, produce enough (in billions) of all necessary cell types to generate organs for in vivo safety, immunogenicity, and efficacy testing. As a part of Quality Assurance (QA)/ Quality Control (QC) testing, perform toxicity, tumorigenicity, and mutagenicity assays. Define storage conditions with high percentage viability and transportability using 4′,6-diamidino-2-phenylindole (DAPI) staining or any alternative more sensitive method. The final goal for this TA in Phase I will be GLP manufacturing of organ cell biobank. In Phase II, leveraging the knowledge from Phase I, performers will scale up manufacturing to GMP for IND enabling studies in large animals.
- Technical Area 3 (TA3): Organ Biofabrication and in vivo testing (Phase I and II): This TA aligns with Phase I to develop biofabrication technologies. Some examples include, but are not limited to, (1) technologies to improve current bioreactors for cost-saving and better performance of the organ, (2) bioink formulations that support anisotropic tissue printing, (3) bioprinting methods to improve printing speed, (4) multi-physics modeling to inform 3D organ design (shape and size of the organ to match the patient), and (5) perfusion system to mature the organ in vitro before transplantation. The main goal of this TA is to PRINT suturable, functional organs that will be transplanted and tested in humanized small animals.