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

PLOS Computational Biology, 2015 · DOI: 10.1371/journal.pcbi.1004309 · Published: June 25, 2015

Spinal Cord Injury Bioinformatics Dermatology

Simple Explanation

A virtual pressure ulcer was created as a platform to test therapies and determine the mechanisms most correlated with unfavorable outcomes. A layer of tissue fed with oxygen and diffusible molecules via blood vessels could develop an ulcer if pressure was applied, by simulating constriction of blood vessels in a circular region. Statistical analyses of simulation outputs revealed that inflammation was an important determinant of ulcer severity and overall tissue damage.

Study Duration

Not specified

Participants

49 patients with spinal cord injury

Evidence Level

Not specified

Key Findings

1
Tissue-level features of the PUABM recapitulated visual patterns of ulcer formation in individuals with SCI.
2
Sensitivity analysis of model parameters suggested that increasing oxygen availability would reduce PU incidence.
3
The PUABM thus shows promise as an adjunct for mechanistic understanding, diagnosis, and design of therapies in the setting of PU.

Research Summary

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. 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.

Practical Implications

Mechanistic Understanding

The PUABM offers insights into the complex interplay of factors involved in pressure ulcer formation, including inflammation, ischemia/reperfusion injury, and tissue damage.

Diagnostic Aid

The model's ability to recapitulate visual features of pressure ulcers suggests its potential as a diagnostic tool to identify patients at high risk of ulcer formation before the ulcers progress.

Therapeutic Design

In silico trials using the PUABM can aid in the design and testing of new treatment regimens, potentially identifying more effective interventions for preventing and treating pressure ulcers.

Study Limitations

1
The PUABM is a two-dimensional model, which may not fully capture the complexity of pressure ulcers that extend in depth through multiple tissue layers.
2
Many parameter values were selected to achieve appropriate qualitative behavior at the cellular or molecular scales due to the lack of appropriate data.
3
The model does not include all potential mechanisms of inflammation.

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