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The Wyss Institute for Biologically Inspired Engineering at Harvard University was formed based on the recognition that breakthrough discoveries cannot change the world if they never leave the laboratory. The Institute's mission is to discover the biological principles that Nature uses to build living things, and to harness these insights to create biologically inspired engineering innovations to advance human health and create a more sustainable world. Since its launch in 2009, the Institute has developed a new model for innovation, collaboration, and technology translation within academia, breaking “silos” to enable collaborations that cross institutional and disciplinary barriers. Institute faculty and staff engage in high‐risk research that leads to transformative breakthroughs. The biological principles uncovered are harnessed to develop new engineering solutions for medicine and healthcare, as well as nonmedical areas, such as energy, architecture, robotics, and manufacturing. These technologies are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and the formation of new start‐ups that are driven by a unique internal business development team including entrepreneurs‐in‐residence with domain‐specific expertise. Here, we describe this novel organizational model that the Institute has developed to change the paradigm of how fundamental discovery, medical technology innovation, and commercial translation are carried out at the academic‐industrial interface.