A Computational, Tissue-Realistic Model of Pressure Ulcer Formation in Individuals with Spinal Cord Injury

• Type of Material: Article
• Authors: Cordelia Ziraldo, University of Pittsburgh; Alexey Solovyev, University of Pittsburgh; Ana Allegretti, University of Pittsburgh; Shilpa Krishnan, Emory University; M. Kristi Henzel, Louis Stokes Cleveland Department of Veterans Affairs Medical Center; Gwendolyn A. Sowa, University of Pittsburgh; David Brienza, University of Pittsburgh; Gary An, University of Pittsburgh; Qi Mi, University of Pittsburgh; Yoram Vodovotz, University of Pittsburgh
• Language: English
• Date: 2015-06-01
• Publisher: PUBLIC LIBRARY SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: © 2015 Ziraldo et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pcbi.1004309
• Title of Journal or Parent Work: PLOS COMPUTATIONAL BIOLOGY
• Volume: 11
• Issue: 6
• Start Page: e1004309
• End Page: e1004309
• Grant/Funding Information: This work was made possible by a grant from the US Department of Education, National Institute on Disability and Rehabilitation Research (NIDRR grant # H133E070024) and an IBM Shared University Research Award to YV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: Biochemistry & Molecular Biology; CLINICAL-TRIALS; MECHANISMS; MYCOBACTERIUM-TUBERCULOSIS; Mathematical & Computational Biology; XANTHINE-OXIDASE; HMGB1; Biochemical Research Methods; ACUTE-CARE; Science & Technology; INFLAMMATION; Life Sciences & Biomedicine; CYTOKINE
• Research Categories: Biology, Molecular; Mathematics; Chemistry, Biochemistry

Abstract

People with spinal cord injury (SCI) are predisposed to pressure ulcers (PU). PU remain a significant burden in cost of care and quality of life despite improved mechanistic understanding and advanced interventions. An agent-based model (ABM) of ischemia/reperfusion-induced inflammation and PU (the PUABM) was created, calibrated to serial images of post-SCI PU, and used to investigate potential treatments in silico. Tissue-level features of the PUABM recapitulated visual patterns of ulcer formation in individuals with SCI. These morphological features, along with simulated cell counts and mediator concentrations, suggested that the influence of inflammatory dynamics caused simulations to be committed to “better” vs. “worse” outcomes by 4 days of simulated time and prior to ulcer formation. Sensitivity analysis of model parameters suggested that increasing oxygen availability would reduce PU incidence. Using the PUABM, in silico trials of anti-inflammatory treatments such as corticosteroids and a neutralizing antibody targeted at Damage-Associated Molecular Pattern molecules (DAMPs) suggested that, at best, early application at a sufficiently high dose could attenuate local inflammation and reduce pressure-associated tissue damage, but could not reduce PU incidence. The PUABM thus shows promise as an adjunct for mechanistic understanding, diagnosis, and design of therapies in the setting of PU.