title: A Computational, Tissue-Realistic Model of Pressure Ulcer Formation in Individuals with Spinal Cord Injury.
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.
authors.affiliation: Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Joint PhD Program in Computational Biology, University of Pittsburgh and Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America; Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Cordelia
authors.initials: C
authors.lastname: Ziraldo
authors.affiliation: Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Mathematics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Alexey
authors.initials: A
authors.lastname: Solovyev
authors.affiliation: Department of Rehabilitation Science and Technology, School of Health and Rehabilitation Science, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Ana
authors.initials: A
authors.lastname: Allegretti
authors.affiliation: Department of Rehabilitation Science and Technology, School of Health and Rehabilitation Science, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: Spinal Cord Injury/Disorders Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, United States of America.
authors.forename: M Kristi
authors.initials: MK
authors.lastname: Henzel
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Gwendolyn A
authors.initials: GA
authors.lastname: Sowa
authors.affiliation: Department of Rehabilitation Science and Technology, School of Health and Rehabilitation Science, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Brienza
authors.affiliation: Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Surgery, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Gary
authors.initials: G
authors.lastname: An
authors.affiliation: Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Sports Medicine and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Qi
authors.initials: Q
authors.lastname: Mi
authors.affiliation: Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Vodovotz
mesh_terms: D000465:Algorithms; D002630:Chemotactic Factors / Q000378:metabolism; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D011312:Pressure; D003668:Pressure Ulcer / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000150:complications*
chemical_list: D002630:Chemotactic Factors