Document Type
Manuscript
Submission Date
2025
Abstract
Introduction: Partial-thickness burn injuries, depending on depth, are distinct from deeper burns in that they can preserve the hair follicle bulb as a source of epithelial stem cells and a modulator of mechanical forces and immune cells. This changes the dynamics of wound healing and is an important consideration for therapeutic decisions. Regardless, patients require appropriate interventions to facilitate proper restoration of the skin to prevent complications like wound infection or sepsis that can occur as sequelae of the disrupted epithelial barrier and systemic inflammatory cascades. Herein, we developed a computational agent-based model of the partial-thickness burn wound environment, the Burn Agent-based Model (BABM), in order to better characterize the complex systems of wound healing and facilitate investigation of novel therapeutic strategies.
Methods: The model was developed using NetLogo and simulates a two-dimensional cross-section of epidermis and dermis containing multiple hair follicles. It includes multiple cell types present in those layers, such as keratinocytes, epithelial stem cells, neutrophils, macrophages, and fibroblasts, as well as key cytokines and chemokines. Burn injuries were implemented as a mechanical “shearing” of the entire epidermis and the superficial portion of the dermis with damage to the immediately deeper tissue. The model encompasses the first three weeks of the post-burn period, including hemostasis and coagulation, inflammation, proliferation, and re-epithelialization.
Results: We successfully created an ABM of the partial-thickness burn wound healing process at the cellular and cytokinetic level. The model implements the mitotic function of epithelial stem cells particularly within hair follicle bulbs, paracrine influences of injured keratinocytes, phagocytic and inflammatory actions of neutrophils and macrophages, migration and extra-cellular matrix deposition by fibroblasts, and the vascular dynamics of dermal capillaries representing the zones of coagulation, stasis, and hyperemia. In addition, the model incorporates multiple cytokines, notably IL1, IL6, TNFa, TGFb, EGF, FGF, PDGF, and VEGF. The model was calibrated to closely follow the cytokine profiles obtained from cytokine multiplex assays of patients hospitalized for burn injuries.
Conclusion: The BABM provides a powerful in-silico framework to study burn wound healing by simulating a small segment of injured skin that can be scaled near infinitely to represent a wound of any size but does not include the wound edge. As the model is refined and further validated, our goal is to allow for model calibration with individualized patient data in order to create a personalized “digital twin” that closely mimics the patient’s physiology and may augment diagnostic or therapeutic decision-making in the clinical setting.
Recommended Citation
Shin, Bryan; Cockrell, Robert; and An, Gary, "The Burn Agent-Based Model (BABM): Developing a Computational Agent-based Model of the Burn Wound Healing Process to Examine Fibrosis and Re-epithelialization After a Partial-thickness Burn Injury" (2025). Larner College of Medicine Fourth Year Advanced Integration Teaching/Scholarly Projects. 52.
https://scholarworks.uvm.edu/m4sp/52
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