TY - JOUR
T1 - An in silico modeling approach to understanding the dynamics of the post-burn immune response
AU - Korkmaz, H Ibrahim
AU - Sheraton, Vivek M
AU - Bumbuc, Roland V
AU - Li, Meifang
AU - Pijpe, Anouk
AU - Mulder, Patrick P G
AU - Boekema, Bouke K H L
AU - de Jong, Evelien
AU - Papendorp, Stephan G F
AU - Brands, Ruud
AU - Middelkoop, Esther
AU - Sloot, Peter M A
AU - van Zuijlen, Paul P M
N1 - Publisher Copyright: Copyright © 2024 Korkmaz, Sheraton, Bumbuc, Li, Pijpe, Mulder, Boekema, de Jong, Papendorp, Brands, Middelkoop, Sloot and van Zuijlen.
PY - 2024
Y1 - 2024
N2 - INTRODUCTION: Burns are characterized by a massive and prolonged acute inflammation, which persists for up to months after the initial trauma. Due to the complexity of the inflammatory process, Predicting the dynamics of wound healing process can be challenging for burn injuries. The aim of this study was to develop simulation models for the post-burn immune response based on (pre)clinical data.METHODS: The simulation domain was separated into blood and tissue compartments. Each of these compartments contained solutes and cell agents. Solutes comprise pro-inflammatory cytokines, anti-inflammatory cytokines and inflammation triggering factors. The solutes diffuse around the domain based on their concentration profiles. The cells include mast cells, neutrophils, and macrophages, and were modeled as independent agents. The cells are motile and exhibit chemotaxis based on concentrations gradients of the solutes. In addition, the cells secrete various solutes that in turn alter the dynamics and responses of the burn wound system.RESULTS: We developed an Glazier-Graner-Hogeweg method-based model (GGH) to capture the complexities associated with the dynamics of inflammation after burn injuries, including changes in cell counts and cytokine levels. Through simulations from day 0 - 4 post-burn, we successfully identified key factors influencing the acute inflammatory response, i.e., the initial number of endothelial cells, the chemotaxis threshold, and the level of chemoattractants.CONCLUSION: Our findings highlight the pivotal role of the initial endothelial cell count as a key parameter for intensity of inflammation and progression of acute inflammation, 0 - 4 days post-burn.
AB - INTRODUCTION: Burns are characterized by a massive and prolonged acute inflammation, which persists for up to months after the initial trauma. Due to the complexity of the inflammatory process, Predicting the dynamics of wound healing process can be challenging for burn injuries. The aim of this study was to develop simulation models for the post-burn immune response based on (pre)clinical data.METHODS: The simulation domain was separated into blood and tissue compartments. Each of these compartments contained solutes and cell agents. Solutes comprise pro-inflammatory cytokines, anti-inflammatory cytokines and inflammation triggering factors. The solutes diffuse around the domain based on their concentration profiles. The cells include mast cells, neutrophils, and macrophages, and were modeled as independent agents. The cells are motile and exhibit chemotaxis based on concentrations gradients of the solutes. In addition, the cells secrete various solutes that in turn alter the dynamics and responses of the burn wound system.RESULTS: We developed an Glazier-Graner-Hogeweg method-based model (GGH) to capture the complexities associated with the dynamics of inflammation after burn injuries, including changes in cell counts and cytokine levels. Through simulations from day 0 - 4 post-burn, we successfully identified key factors influencing the acute inflammatory response, i.e., the initial number of endothelial cells, the chemotaxis threshold, and the level of chemoattractants.CONCLUSION: Our findings highlight the pivotal role of the initial endothelial cell count as a key parameter for intensity of inflammation and progression of acute inflammation, 0 - 4 days post-burn.
KW - burns
KW - computational modeling
KW - immune response
KW - inflammation
KW - wound healing
UR - http://www.scopus.com/inward/record.url?scp=85184731786&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2024.1303776
DO - 10.3389/fimmu.2024.1303776
M3 - Article
C2 - 38348032
SN - 1664-3224
VL - 15
SP - 1303776
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 1303776
ER -