Human Digital Twins in Personalized Medicine: A Systematic Review and Bibliometric–Thematic Synthesis of Methodological Advances and Clinical Applications

Human digital twins (HDTs) are patient-specific computational models that combine medical imaging, physiological measurements and predictive algorithms. They are moving from an exciting concept to a realistic clinical opportunity. The key question is no longer whether HDTs can be built. The key question is which methods are mature enough to support clinical decisions and what is still missing for routine use. This systematic review maps the methodological landscape of HDTs and highlights practical bottlenecks that limit clinical translation. A PRISMA 2020 guided search of PubMed, Scopus, IEEE Xplore, and the Cochrane Library, covering publications from 2016 to 2026, identified 151 eligible studies. Bibliometric mapping and thematic synthesis were used to characterize research clusters, computational paradigms, and collaboration patterns. Three dominant application streams were identified: cardiovascular HDTs for hemodynamic simulation and procedural planning, musculoskeletal HDTs for biomechanics-driven orthopedic innovation, and neurological HDTs integrating neuroimaging with computational neuroscience. Across domains, the strongest technical trend is the rise in hybrid pipelines that combine physics-based simulation, including finite element and computational fluid dynamics models, with machine learning for segmentation, parameter identification, reduced-order modeling, and faster inference. However, reporting of verification, validation, uncertainty quantification, and explicit context of use remains uneven and prospective clinical evidence is still limited. Overall, the literature shows rapid progress toward clinically credible HDTs, while highlighting the need for scalable computation, standardized credibility pipelines, and workflow-integrated platforms to support safe and reproducible clinical adoption.