Developing a High-throughput Bioprinting Platform for 3D iPSC-derived Liver Tissues for Early Drug Screening

SummaryCurrent drug discovery and development practices have resulted in considerably long development time frames and low success rates of new drugs reaching marketFew improvements on efficiency and poor cost versus benefits in Randamp D have also caused post approval costs as high as $billion inTogetherthese factors drive the demand to improve current practices and turn to new innovative technologies that are able to facilitate the introduction of more successful drugs with higher efficiency and cost effectivenessIt is well recognized that a key bottleneck in the pharmaceutical Randamp D sector is the lack of appropriate validation tools for accurate selection of prime drug candidates in the early stagesTo circumvent this issuenew technologies such as high throughput screeningHTSplatforms are emergingIn additionpharmaceutical companies are adaptingD tissue culture platforms to better recapitulate the in vivo microenvironment to provide more physiologically relevant predictive dataUltimatelyan HTS system that incorporatesD biomimetic tissue cultures would be a significant advancement to current technologies in early stage drug developmentThis proposal aims to develop a high throughput optical projectionhTOPbioprinter that can directly print human liver tissue models within conventional multi well cell culture plates for applications in high throughput preclinical drug screeningSpecific Aimwill focus on the development of the hTOP bioprinter and its use to createD hydrogel constructs within awell cell culture plateIn Specific Aimwe will optimize and characterize the ability to reproducibly print identical constructs within multiple wells and also the flexibility to print various designsIn Specific Aimwe will demonstrate the use of hTOP to bioprintD human liver tissues in a high throughput manner using iPSC derived hepatocytes and liver specific supportive cells to produce a physiologically relevant biomimetic modelCell viability and hepatic function will be investigated along with studies on drug metabolism and drug induced hepatotoxicity using ourD biomimetic human liver modelOur hTOP bioprinting platform will serve as a commercially powerful instrument for the mass production of in vitroD tissue models for early stage high throughput drug screeningMore specificallythe hTOP bioprinter offers microscale printing resolution and superior printing speed compared to traditional bioprintersFurthermorethe bioprinted iPSC derived human liver model will provide a more reliable and clinically relevant platform to test drug induced hepatotoxicity during preclinical trialsWhile the hTOP will be used to demonstrate the fabrication of a human liver biomimetic model in this workit can also be readily adapted to print other biomimetic tissue models such as heartkidneyand nerve tissuesSuccess of this project will significantly improve the predictive accuracy of preclinical drug studies and lower the cost of drug development towards improving public health Project Narrative The project seeks to develop a high throughputD bioprinting platform to create in vitro functional human liver tissues using human induced pluripotent stem cellsSuch tissue models can facilitate preclinical drug screening and disease studiesSuccess of this proposal would lead to significant reduction in cost for drug development and time to clinical use