4D Bioprinting For Regenerative Medicine Solutions

Despite great scientific and clinical successes, few tissue engineering products have so far made their way to the industrial and commercial phase, depriving patients to benefit from innovative treatments. Producing advanced therapy medicinal products remains a cumbersome process with costs, reproducibility and scalability issues. Automation of production processes should be key to achieve quality controlled and repeatable biomanufacturing. Poietis develops biomanufacturing solutions based on bioprinting technologies for the design and the production of tissues, like the full thickness skin model Poieskinu00ae.The fabrication process follows three main steps: (1) tissue design where the 3D patterns of cells and materials are defined through a proprietary tissue CAD software; (2) tissue biofabrication consisting in the layer-by-layer deposition of collagen, fibroblasts and keratinocytes; (3) tissue maturation during which cell patterns evolve towards the final functional tissue architecture. Biofabrication is performed using the proprietary Next-Generation Bioprinting platform combining microvalve and laser assisted bioprinting. Unit controls is performed using embedded image analysis tools to assess production quality. The Quality-by-Design methology is used to determine CMA (critical material attributes) and CPP (critical process parameters).We demonstrate a control over the 3D cell organization and a relation between the initial 3D cell pattern and the cell reorganization dynamics. The use of the Quality-By-Design methodology enabled to hierarchize the CMA and CPP and consequently incrementaly improve the reproducibility and quality of the produced tissues. The biofabrication strategy described here is generic and can be applied to the design and production of any tissue. The routine production of Poieskinu00ae for in vitro research applications demonstrates the industrial maturity of bioprinting and is a key milestone towards the development of clinical bioprinters for the production of tissue grafts.