Healing I: Introduction

Healing is the physiological process by which the body restores the integrity and function of damaged tissues following injury. It involves a coordinated interplay of cellular proliferation, extracellular matrix remodeling, and growth factor signaling. The extent and nature of the tissue damage determine whether healing occurs by resolution, regeneration, or replacement.

Resolution

Resolution represents the most complete form of healing, occurring when the injury is minimal and tissue architecture remains largely intact. Damaged cells recover their normal structure and function without residual scarring. An example is a mild sunburn, where epithelial cells repair sublethal damage through intracellular repair mechanisms, and the tissue returns to its pre‑injury state once inflammation subsides.

Regeneration

Regeneration involves the replacement of lost cells with new ones that are structurally and functionally identical. It occurs in tissues containing labile or stable cell populations capable of proliferation. The liver exemplifies this process: hepatocytes re-enter the cell cycle under the influence of growth factors such as hepatocyte growth factor (HGF) and transforming growth factor-alpha (TGF-alpha), thereby restoring hepatic mass through controlled mitosis. However, when the extracellular matrix framework is disrupted or damage is extensive, regeneration may be incomplete, and scar formation often accompanies the repair process.

Replacement

Replacement, or repair by fibrosis, predominates in tissues composed of permanent cells—such as cardiomyocytes and neurons—that have little or no capacity for division. Following a myocardial infarction, for instance, necrotic cardiomyocytes are removed by macrophages and replaced by granulation tissue rich in fibroblasts and new capillaries. Over time, this tissue matures into a dense collagenous scar. Although this fibrous matrix maintains structural stability, it lacks the contractile and conductive properties of the original myocardium, resulting in permanent functional loss.