Tissue regeneration is an active multiplex process involving the dynamic inflammatory microenvironment. Under a normal physiological framework, inflammation is necessary for the systematic immunity including tissue repair and regeneration as well as returning to homeostasis. Inflammatory cellular response and metabolic mechanisms play key roles in the well-orchestrated tissue regeneration. If this response is dysregulated, it becomes chronic, which in turn causes progressive fibrosis, improper repair, and autoimmune disorders, ultimately leading to organ failure and death. Therefore, understanding of the complex inflammatory multiple player responses and their cellular metabolisms facilitates the latest insights and brings novel therapeutic methods for early diseases and modern health challenges. This review discusses the recent advances in molecular interactions of immune cells, controlled shift of pro- to anti-inflammation, reparative inflammatory metabolisms in tissue regeneration, controlling of an unfavorable microenvironment, dysregulated inflammatory diseases, and emerging therapeutic strategies including the use of biomaterials, which expand therapeutic views and briefly denote important gaps that are still prevailing.
Cellular metabolism plays a major role in the regulation of inflammation. The inflammatory macrophages undergo a wide‐range of metabolic rewriting due to the production of significant amount of itaconate metabolite from cis‐aconitate in the tricarboxylic acid cycle. This itaconate molecule has been recently described as a promising immunoregulator. However, its function and mode of action on macrophages and tissue repair and regeneration are yet unclear. Herein, the itaconate‐derivative dimethyl itaconate (DMI) suppresses the IL‐23/IL‐17 inflammatory axis‐associated genes and promotes antioxidant nuclear factor erythroid 2‐related factor 2 target genes. The poly‐ε‐caprolactone (PCL)/DMI nanofibers implanted in mice initially maintain inflammation by suppressing anti‐inflammatory activity and particular inflammation, while at later stage promotes anti‐inflammatory activity for an appropriate tissue repair. Furthermore, the PCL/DMI nanofiber patches show an excellent myocardial protection by reducing infarct area and improving ventricular function via time‐dependent regulation of myocardium‐associated genes. This study unveils potential DMI macrophage modulatory functions in tissue microenvironment and macrophages rewriting for proper tissue repair.
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