The Industry 4.0 concept refers to automation and data ex-change in manufacturing technologies, which includes tech-nologies for cell therapy product manufacturing. An importantaspect of this concept is the development and use of DigitalTwins. A Digital Twin is a digital representation of a product orprocess that is used to optimize the design and use of saidproduct or process. In this opinion article, we show that suchDigital Twins have already been developed for a variety oftissue engineering processes. Using skeletal tissue engineer-ing as a case study, we discuss a number of models at variousstages of use between bench and bedside and ranging frompure data-driven models to models built on known mecha-nisms and first principles. Finally, we emphasize the impor-tance of data collection and model validation to ensure, amongst others, compliance to regulatory guidelines.