Abstract
Implanted medical devices often trigger immunological and inflammatory reactions from surrounding tissues. The foreign body-mediated tissue responses may result in varying degrees of fibrotic tissue formation. There is an intensive research interest in the area of wound healing modeling, and quantitative methods are proposed to systematically study the behavior of this complex system of multiple cells, proteins, and enzymes. This paper introduces a kinetics-based model for analyzing reactions of various cells/proteins and biochemical processes as well as their transient behavior during the implant healing in 2-dimensional space. In particular, we provide a detailed modeling study of different roles of macrophages (MΦ) and their effects on fibrotic reactions. The main mathematical result indicates that the stability of the inflamed steady state depends primarily on the reaction dynamics of the system. However, if the said equilibrium is unstable by its reaction-only system, the spatial diffusion and chemotactic effects can help to stabilize when the model is dominated by classical and regulatory macrophages over the inflammatory macrophages. The mathematical proof and counter examples are given for these conclusions.
Highlights
Intensive research efforts have been focusing on developing mechanistic computational models for wound healing related processes
Enzyme, growth factors, and proteins participate at different stages of the wound healing reactions, and they form a network of signaling pathways that in turn leads to inflammatory, angiogenesis, and fibrotic reactions
It is commonly accepted that implants may cause foreign body reactions that are initiated with implant-mediated fibrin clot formation, followed by acute inflammatory responses [4, 5]
Summary
Intensive research efforts have been focusing on developing mechanistic computational models for wound healing related processes. The implantrecruited fibroblasts synthesize chains of amino acids called procollagen, a process that is activated by growth factors, including in particular type-β transforming growth factor (TGF-β) [6, 7] to become collagen, the dominant ingredient of the extracellular matrix (ECM) [8] These processes may, differ slightly between dermal wound healing and implantation when it comes to specific activation and inhibition loops of reactions. Our primary goal in this paper is to use computational modeling to study the fibrotic reaction process following implantation with specific attention given to the effects caused by varying the mix of different phenotypes of MΦ.
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