PT - JOURNAL ARTICLE AU - Amelie Erben AU - Thomas Kellerer AU - Josefine Lissner AU - Constanze Eulenkamp AU - Thomas Hellerer AU - Hauke-Clausen-Schaumann AU - Stefanie Sudhop AU - Michael Heymann TI - Engineering Principles and Algorithmic Design Synthesis for Ultracompact Bio-Hybrid Perfusion Chip AID - 10.1101/2022.03.16.484492 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.03.16.484492 4099 - http://biorxiv.org/content/early/2022/03/18/2022.03.16.484492.short 4100 - http://biorxiv.org/content/early/2022/03/18/2022.03.16.484492.full AB - Bioinspired 3D microfluidic systems that combine vascularization with extracellular matrix architectures of organotypic geometry, composition and biophysical traits can help advance our understanding of microorgan physiology. Here, two-photon stereolithography is adopted to fabricate freestanding perfusable 3D cell scaffolds with micrometer resolution from gelatin methacryloyl hydrogel derived from extracellular matrix protein. As a proof of concept, we introduce an ultracompact bio-hybrid chip layout to demonstrate perfusion and cell seeding of double-digit μm proteinaceous channels. This perfusion chip consists of a standardized microfluidic interface fabricated from standard resin and a GM10 bioink channel printed atop of this interface. In addition, we demonstrate that algorithmic design synthesis can recapitulate intact alveoli and capillary networks with tunable design parameters to implement vascularized alveolar tissue models. This approach will allow for a systematic investigation of cell-cell and tissue dynamics in response to defined structural, mechanical and bio-molecular cues and is ultimately scalable to fabricate organ-on-a-chip systems.Competing Interest StatementJosefine Lissner is employee of Hyperganic Group GmbH