Digital twins in healthcare: A systematic review of current applications, frameworks, and future directions
Valeria Calcaterra, Luca Guardamagna, Alessandro Gatti, Virginia Rossi, Pamela Patanè, Luca Marin, Matteo Vandoni, Gianvincenzo ZuccottiObjective
This systematic review aims to evaluate current digital twin (DT) applications in healthcare, explore their technological foundations, and propose a roadmap for scalable, patient-centered implementation.
Methods
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, a systematic search was conducted across Medline, Scopus, Web of Science, and EBSCO up to May 2025. Eligible studies included peer-reviewed research on DT applications in clinical or healthcare settings involving human or patient-related data. Methodological quality was assessed using appropriate Joanna Briggs Institute critical appraisal tools based on study design. The systematic review protocol was prospectively registered in Prospective Register of Systematic Reviews (registration number: CRD420251120304).
Results
26 studies were included, with most published between 2023 and 2025. DT applications spanned diagnostics, therapy optimization, physiological monitoring, and system-level modeling. Simulation-based designs dominated, often integrating artificial intelligence, internet of things, and machine learning. While several studies reported strong technical performance (e.g. up to 96.3% accuracy), real-world clinical integration was rare. Notable outcomes included better glycemic control, pain management, and disease progression prediction. Barriers included insufficient infrastructure detail, limited validation, and equity concerns. The roadmap highlights three enablers: privacy-preserving, validation pipelines, and interoperability.
Conclusion
DTs offer transformative potential for predictive, personalized, and participatory healthcare. Realizing clinical impact requires bridging the translational gap and scaling personalization. This review outlines key strategies for interdisciplinary innovation and deployment of DTs in healthcare.