Tissue Repair and Fibrosis

Tissue repair following injury involves two fundamental processes: regeneration (replacement of damaged tissue with identical functional cells) and fibrosis (replacement with connective tissue scar). The repair process proceeds through four overlapping phases: hemostasis (platelet plug and fibrin clot formation within minutes), inflammation (neutrophil then macrophage infiltration over hours to days, clearing debris and releasing cytokines), proliferation (fibroblast activation, angiogenesis, granulation tissue formation, and re-epithelialization over days to weeks), and remodeling (collagen cross-linking and maturation over weeks to months, achieving maximum 80% of original tissue strength). Fibrosis occurs when the balance tips toward excessive extracellular matrix (ECM) deposition over degradation. The key mediator is transforming growth factor-beta (TGF-β), which activates fibroblasts to differentiate into myofibroblasts — contractile cells that produce large quantities of collagen types I and III, fibronectin, and other ECM components. Matrix metalloproteinases (MMPs) degrade ECM, while tissue inhibitors of metalloproteinases (TIMPs) prevent degradation; an imbalance favoring TIMPs results in net ECM accumulation and progressive fibrosis. Pathological fibrosis can affect any organ: pulmonary fibrosis (IPF), hepatic fibrosis/cirrhosis, renal fibrosis, cardiac fibrosis post-MI, and skin fibrosis (keloids, scleroderma). Factors impairing...