The goal of the 3-D Tissue Bioprinting program is to advance the process of discovery and development of new medicines by developing new assay models that better predict the effects of drugs in humans. 3-D tissue models that mimic characteristics of live human tissues are produced on microplates to test effectiveness and toxicity of small molecules or other therapeutics. Access to 3-D tissue models in microplate format leverages tissue engineering/organogenesis, stem cell and disease biology, and use of in situ detection technologies (technologies that can be used to detect something in intact tissue) for tissue characterization and testing of drugs’ effects.
The 3-D Tissue Bioprinting program’s primary focus is the development of “disease-relevant tissue models” to reduce the predictability gap between results from current 2-D cell-based assays and results from testing in humans. The program team focuses on many different treatment methods and aims to overcome translational barriers toward the development of urgently needed treatments for unmet medical needs.
- Develop a portfolio of bioprinted normal and disease tissue models in a microplate screening format using primary or iPSC-derived cells.
- Develop methods to quantitatively determine disease phenotypes of the 3-D bioprinted tissues and determine the effects of therapeutic treatment-induced changes in the tissue, in a screening format. Different technologies with a range of resolution, depth of tissue penetration and sample processing throughput are being used, including confocal fluorescence microscopy techniques, and measurements of biomolecules from the supernatant using the LUMINEX bead technology or mass spectrometry methods.
- Implement novel technologies to more effectively and rapidly monitor tissue maturation, including noninvasive and non-destructive imaging technologies, such as optical coherence tomography and reflectance confocal microscopy; imaging mass spectrometry, such as MALDI, which will be applied to the detection of biomolecules that are challenging to detect by immunostaining, and transcriptomics signatures by RNAseq.
- Develop high-throughput tissue clearing and 3-D segmentation computational approaches for the practical implementation of screening using fluorescence imaging techniques.
- Establish partnerships to implement technological advances that enable to increase the complexity of the bioprinted tissues and their ease of use for screening, including perfusion to mimic vasculature, and microfluidics platforms for automated media exchanges and media sampling.
- Apply artificial intelligence approaches for quality control of tissue maturation as well as correction of disease phenotypes by treatment with therapeutic interventions.
- Focus on technical standardization, rigorous quality control, reproducibility, pharmacological benchmarking, and thoughtful integration into the drug discovery and development pipeline. Share results so that the knowledge derived from different improvements will be available to the community through publications and posting on the website.
- Expand routine bioprinting of live human tissues for drug development applications with well-characterized protocols and procedures developed at NCATS to additional tissues and organ systems through internal efforts and collaborative projects.