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In Silico Modeling: Methods and Applications to Trauma and Sepsis

Vodovotz, Yoram PhD1,2; Billiar, Timothy R. MD1

doi: 10.1097/CCM.0b013e31829a6eb4
Concise Definitive Review

Objectives: To familiarize clinicians with advances in computational disease modeling applied to trauma and sepsis.

Data Sources: PubMed search and review of relevant medical literature.

Summary: Definitions, key methods, and applications of computational modeling to trauma and sepsis are reviewed.

Conclusions: Computational modeling of inflammation and organ dysfunction at the cellular, organ, whole-organism, and population levels has suggested a positive feedback cycle of inflammation → damage → inflammation that manifests via organ-specific inflammatory switching networks. This structure may manifest as multicompartment “tipping points” that drive multiple organ dysfunction. This process may be amenable to rational inflammation reprogramming.

1Department of Surgery, University of Pittsburgh, Pittsburgh, PA.

2Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA.

Supported, in part, by grants R01GM67240, R33HL089082, R01HL080926, R01AI080799, R01HL76157, and R01DC008290 from the National Institutes of Health; grant 0830-370-V601 from National Science Foundation; a Shared University Research Award from IBM; and grants from the Commonwealth of Pennsylvania, the Pittsburgh Lifesciences Greenhouse, and the Pittsburgh Tissue Engineering Initiative/Department of Defense.

Dr. Vodovotz received grant support from the National Institutes of Health (NIH) (P50-GM-53789 and UO1-DK072146) and the National Institute on Disability and Rehabilitation Research (NIDRR) (H133E070024). Dr. Vodovotz has received a U.S. Patent for “Modeling Wound Healing” (No. 8,165,819) and U.S. Patent applications for “Self-Regulating Device for Modulating Inflammation” (No. 13/121,013) and “Methods for Modeling Hepatic Inflammation” (No. 13/700,244). Dr. Billiar’s institution received grant support from NIH. Drs. Billiar and Vodovotz received article research support from NIH. Dr. Vodovotz received article research support from NIDRR. Dr. Vodovotz is the cofounder of Immunetrics. Drs. Billiar and Vodovotz own stock options with Immunetrics. Dr. Vodovotz’s laboratory received a high-performance computing platform valued at approximately $500,000 as a Shared University Award from IBM.

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© 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins