Arkadiusz Gertych

Contemporary analyses focused on a limited number of clinical and molecular biomarkers have been unable to accurately predict clinical outcomes in pancreatic ductal adenocarcinoma. Here we describe a precision medicine platform known as the Molecular Twin consisting of advanced machine-learning models and use it to analyze a dataset of 6,363 clinical and multi-omic molecular features from patients with resected pancreatic ductal adenocarcinoma to accurately predict disease survival (DS). We show that a full multi-omic model predicts DS with the highest accuracy and that plasma protein is the top single-omic predictor of DS. A parsimonious model learning only 589 multi-omic features demonstrated similar predictive performance as the full multi-omic model. Our platform enables discovery of parsimonious biomarker panels and performance assessment of outcome prediction models learning from resource-intensive panels. This approach has considerable potential to impact clinical care and democratize precision cancer medicine worldwide.

Tendons and ligaments have a poor innate healing capacity, yet account for 50% of musculoskeletal injuries in the United States. Full structure and function restoration postinjury remains an unmet clinical need. This study aimed to assess the application of novel three dimensional (3D) printed scaffolds and induced pluripotent stem cell‐derived mesenchymal stem cells (iMSCs) overexpressing the transcription factor Scleraxis (SCX, iMSC^SCX+) as a new strategy for tendon defect repair. The polycaprolactone (PCL) scaffolds were fabricated by extrusion through a patterned nozzle or conventional round nozzle. Scaffolds were seeded with iMSC^SCX+ and outcomes were assessed in vitro via gene expression analysis and immunofluorescence. In vivo, rat Achilles tendon defects were repaired with iMSC^SCX+‐seeded microgrooved scaffolds, microgrooved scaffolds only, or suture only and assessed via gait, gene expression, biomechanical testing, histology, and immunofluorescence. iMSC^SCX+‐seeded on microgrooved scaffolds showed upregulation of tendon markers and increased organization and linearity of cells compared to non‐patterned scaffolds in vitro. In vivo gait analysis showed improvement in the Scaffold + iMSC^SCX+‐treated group compared to the controls. Tensile testing of the tendons demonstrated improved biomechanical properties of the Scaffold + iMSC^SCX+ group compared with the controls. Histology and immunofluorescence demonstrated more regular tissue formation in the Scaffold + iMSC^SCX+ group. This study demonstrates the potential of 3D‐printed scaffolds with cell‐instructive surface topography seeded with iMSC^SCX+ as an approach to tendon defect repair. Further studies of cell‐scaffold constructs can potentially revolutionize tendon reconstruction by advancing the application of 3D printing‐based technologies toward patient‐specific therapies that improve healing and functional outcomes at both the cellular and tissue level.