Introduction Wound healing is a physiological process involving tissue repair in response to injury involving a complex interaction of various cell types, cytokines, and inflammatory mediators. The overall process protects underlying structures from further damage. Hemostasis, inflammation, granulation, and remodeling. Certain conditions such as diabetes, peripheral vascular disease, and malnutrition can limit the body’s ability to heal itself, thus resulting in complications. 2/3/2025 2
Wound Healing Time Course 2/3/2025 tissue repair mechanisms by Shallo A, 3
Con… 2/3/2025 4
Stages Exudative stage (day 1–4) Hemostasis : limits blood loss from the wound via vasoconstriction. There is a release of inflammatory mediators (growth factors, chemokines, and cytokines) via the activation of platelets. Inflammation : clears cellular debris through phagocytosis. There is a migration of inflammatory cells that facilitate tissue regeneration (via growth factors) 2/3/2025 5
Proliferative stage (day 2–16) Granulation : lays the framework for new connective tissue and vasculature Type III Collagen, poor tensile strength. 2/3/2025 6
Remodeling stage (day 5–25): modifies the wound contents to increase its tensile strength May last years after an injury Apoptosis of excess cells Degradation and alignment of collagen fibers 2/3/2025 7
Granulation Tissue Hallmark of wound healing. Term comes from soft, pink, granular appearance when viewed from the surface of a wound Histology: Proliferation of small blood vessels and fibroblasts; tissue often edematous 2/3/2025 8
GT Granulation Tissue 2/3/2025 9
Types of Wound Healing Regeneration (epithelialization) is the process of returning the site of injury to its original state. This is seen in re-epithelialization after having minor lacerations. Preservation of the basement membrane and a relatively intact ECM (e.g., collagen, adhesive proteins) Reparation (or tissue repair, a form of wound healing) is the process of generating a scar or less functional tissue with a different form and/or composition of the original tissue. Does not restore complete functionality 2/3/2025 10
Resolution of Inflammation: “Regeneration” vs. “Healing” 2/3/2025 11
As per their proliferative capacity, cells can be Labile (continuously dividing) tissues Hematopoietic cells Surface epithelium (skin, mucosa) Stable tissues ( G0 stage of the cell cycle ) Parenchyma of liver , kidney, and pancreas Endothelial cells, fibroblasts, and smooth muscle cells Permanent tissues Terminally differentiated cells of nervous system, cardiac myocytes Skeletal muscle cells? 2/3/2025 12
So, how repair process comes in to being? The regeneration of injured cells and tissues involves cell proliferation , which is driven by growth factors and is critically dependent on the integrity of the ECM , and by the development of mature cells from tissue stem cells. 2/3/2025 13
Cell Proliferation: Signals and Control Mechanisms Remnants of the injured tissue (which attempt to restore normal structure) Vascular endothelial cells (to create new vessels that provide the nutrients needed for the repair process) Fibroblasts (the source of the fibrous tissue that forms the scar to fill defects that cannot be corrected by regeneration) The two main factors determining cell proliferation Intrinsic proliferative capacity Presence of tissue stem cells 2/3/2025 14
2/3/2025 tissue repair mechanisms by Shallo A, 15
An example of healing by fibrosis: Myocardial Infarction 2/3/2025 16 Edge of acute infarct
Mechanisms Angiogenesis Deposition of Connective Tissue Activation of Fibroblasts Remodeling of Connective Tissue 2/3/2025 17
Reparation Primary intention: when the tissue surface edges have been approximated Small defect with little risk of complications and/or infection Secondary intention: when there are significant tissue losses and the wound surface cannot be brought together (e.g., lacerations, burns, and ulcers) Scar formation occurs with a higher risk of infection Tertiary or delayed primary intention: when there is a need to delay the closure of a wound (due to contamination risk, poor circulation, etc.) 2/3/2025 18
Ulcers: an example of healing by 2 nd intention 2/3/2025 19
Factors affecting repair Local Ongoing inflammation (infection, foreign body) Tissue under tension (immobility) Inadequate perfusion Degree of exudate removal Tissue type Systemic Diabetes, Heart failure, Pulmonary diseases, malnutrition Drugs (steroids) Smoking 2/3/2025 20
Complication of wound healing 1. Dehiscence Complete Partial 2/3/2025 21
Abnormal wound healing 2. Keloids Overgrowth of translation tissue causing disfiguring scar beyond the edge of wound Firm, rubbery lesions or shiny, fibrous nodules and can vary from pink to the color of the person's skin or red to dark brown in color 2/3/2025 22
Pathogenesis Excessive Fibroblast proliferation TGF-beta activity Genetic African, blacks Asian descents Predilection sites Upper chest, shoulders, upper back, and head and neck, especially on the ear Keloids never regress, they grow bigger as time passes 2/3/2025 23
3. Hypertrophic scars Raised scars that do not grow beyond the boundaries of the original wound. Made of wavy and linearly arranged array of collagen parallel to surface epithelia 2/3/2025 24