In Silico Perspectives on Bone Regeneration: From Virtual Patients to Living Implants

Digital Twin is a classical engineering concept referring to a virtual representation (in silico model) of a physical object or system across its lifecycle. In healthcare, the term is used more loosely to refer to an in silico model that is informed by patient-specific data and/or used for clinical decision support or personalization of therapeutic solutions. The underlying model technology ranges from purely data-driven (bioinformatics, AI) to mechanistic models, depending on the available knowledge and the question to be answered. Recently, the European Commission launched a new flagship initiative, entitled the Virtual Human Twin [1], which will see the construction of a federated public infrastructure that will facilitate the creation and credibility assessment of digital twins across the human body. A comprehensive roadmap to inform this initiative has been put together by the engaged ecosystem [2]. After providing the broader context of the Virtual Human Twin, I will discuss a number of digital twins – accompanied by dedicated in vitro and in vivo studies - developed in the context of skeletal tissue engineering, and bone regeneration more specifically [3]. Models focusing on the cellular part of the TE product look into predicting and optimizing differentiation of patient-derived progenitor cells, using a skeletal cell atlas as a reference. Biomaterial models assist in the design and printing of 3D scaffolds that enhance bone ingrowth [4]. The digital twin of an in-house developed perfusion bioreactor system allows to interpret, interpolate and enhance the in-line sensor read-outs. Finally, models of the in vivo processes focus on understanding the biological complexity and predicting effects of therapeutic strategies in the patient, with a special focus on the agent-based modeling of inflammatory phase [5] and its interaction with the mechanical fixation. These examples will demonstrate how digital twins in TE contribute to making the bridge between in vitro and in vivo processes and thereby assist in the translation from the laboratory to the patient.