Inflammation and metabolism in tissue repair and regeneration

Abstract

Tissue repair after injury is a complex, metabolically demanding process. Depending on the tissue's regenerative capacity and the quality of the inflammatory response, the outcome is generally imperfect, with some degree of fibrosis, which is defined by aberrant accumulation of collagenous connective tissue. Inflammatory cells multitask at the wound site by facilitating wound debridement and producing chemokines, metabolites, and growth factors. If this well-orchestrated response becomes dysregulated, the wound can become chronic or progressively fibrotic, with both outcomes impairing tissue function, which can ultimately lead to organ failure and death. Here we review the current understanding of the role of inflammation and cell metabolism in tissue-regenerative responses, highlight emerging concepts that may expand therapeutic perspectives, and briefly discuss where important knowledge gaps remain.

Learning from regeneration research organisms: The circuitous road to scar free wound healing

“…The inflammation phase initiates the wound healing process and begins when blood vessel disruption occurs (Eming et al, 2007, 2014, 2017; LeBert and Huttenlocher, 2014; Rosique et al, 2015). Broken blood vessels lead to the release of clotting factors that cause the blood to coagulate and form a fibrin clot (LeBert and Huttenlocher, 2014; Rosique et al, 2015).…”

“…Broken blood vessels lead to the release of clotting factors that cause the blood to coagulate and form a fibrin clot (LeBert and Huttenlocher, 2014; Rosique et al, 2015). The fibrin clot serves many purposes, including cessation of bleeding and provision of a temporary matrix for cellular migration (Eming et al, 2007, 2014, 2017). Damage to the tissue releases mitogens such as Tissue Factor and Tumor Necrosis Factor-alpha (TNF-α) which help to recruit immune cells to the injury site (Eming et al, 2007, 2014, 2017).…”

“…The fibrin clot serves many purposes, including cessation of bleeding and provision of a temporary matrix for cellular migration (Eming et al, 2007, 2014, 2017). Damage to the tissue releases mitogens such as Tissue Factor and Tumor Necrosis Factor-alpha (TNF-α) which help to recruit immune cells to the injury site (Eming et al, 2007, 2014, 2017). Additionally, platelets are recruited into the fibrin clot from the vasculature, which then secrete growth factors and chemokines to attract immune cells to the wound bed (Eming et al, 2007, 2014, 2017; LeBert and Huttenlocher, 2014; Mescher et al, 2017; Rosique et al, 2015).…”

“…Damage to the tissue releases mitogens such as Tissue Factor and Tumor Necrosis Factor-alpha (TNF-α) which help to recruit immune cells to the injury site (Eming et al, 2007, 2014, 2017). Additionally, platelets are recruited into the fibrin clot from the vasculature, which then secrete growth factors and chemokines to attract immune cells to the wound bed (Eming et al, 2007, 2014, 2017; LeBert and Huttenlocher, 2014; Mescher et al, 2017; Rosique et al, 2015). Neutrophils arrive to the wound and eliminate microorganisms within the wound bed by phagocytosis and the release of antimicrobial granules (MacLeod and Mansbridge, 2016; Willenborg and Eming, 2014).…”

Mechanisms of urodele limb regeneration

“…The immune system plays an important role in wound repair and regeneration (for reviews see Eming, Wynn, & Martin, 2017; Mescher 2017; Mescher, Neff & King, 2017). Macrophages of the innate immune system are a central mediator of wound repair in mammals.…”