Which phase of wound healing are buds of granulation tissue generated?

The body is a complex and remarkable machine, and the dynamic process of wound healing is a great example of how our body’s different systems, along with the proper wound care products, work together to repair and replace devitalized tissues. But how, exactly, does our body heal?

When the skin is injured, our body sets into motion an automatic series of events, often referred to as the “cascade of healing,” in order to repair the injured tissues. The cascade of healing is divided into these four overlapping phases: Hemostasis, Inflammatory, Proliferative, and Maturation.

Phase 1: Hemostasis Phase

Hemostasis, the first phase of healing, begins at the onset of injury, and the objective is to stop the bleeding. In this phase, the body activates its emergency repair system, the blood clotting system, and forms a dam to block the drainage. During this process, platelets come into contact with collagen, resulting in activation and aggregation. An enzyme called thrombin is at the center, and it initiates the formation of a fibrin mesh, which strengthens the platelet clumps into a stable clot.

Phase 2: Defensive/Inflammatory Phase

If Phase 1 is primarily about coagulation, the second phase, called the Defensive/Inflammatory Phase, focuses on destroying bacteria and removing debris—essentially preparing the wound bed for the growth of new tissue.

The 4 phases of wound healing. Healing begins with Hemostasis.

During Phase 2, a type of white blood cells called neutrophils enter the wound to destroy bacteria and remove debris. These cells often reach their peak population between 24 and 48 hours after injury, reducing greatly in number after three days. As the white blood cells leave, specialized cells called macrophages arrive to continue clearing debris. These cells also secrete growth factors and proteins that attract immune system cells to the wound to facilitate tissue repair. This phase often lasts four to six days and is often associated with edema, erythema (reddening of the skin), heat and pain.

Phase 3: Proliferative Phase

Once the wound is cleaned out, the wound enters Phase 3, the Proliferative Phase, where the focus is to fill and cover the wound.

The Proliferative phase features three distinct stages: 1) filling the wound; 2) contraction of the wound margins; and 3) covering the wound (epithelialization).

During the first stage, shiny, deep red granulation tissue fills the wound bed with connective tissue, and new blood vessels are formed. During contraction, the wound margins contract and pull toward the center of the wound. In the third stage, epithelial cells arise from the wound bed or margins and begin to migrate across the wound bed in leapfrog fashion until the wound is covered with epithelium. The Proliferative phase often lasts anywhere from four to 24 days.

Phase 4: Maturation Phase

During the Maturation phase, the new tissue slowly gains strength and flexibility. Here, collagen fibers reorganize, the tissue remodels and matures and there is an overall increase in tensile strength (though maximum strength is limited to 80% of the pre-injured strength). The Maturation phase varies greatly from wound to wound, often lasting anywhere from 21 days to two years.

The healing process is remarkable and complex, and it is also susceptible to interruption due to local and systemic factors, including moisture, infection, and maceration (local); and age, nutritional status, body type (systemic). When the right healing environment is established, the body works in wondrous ways to heal and replace devitalized tissue.

In adults, optimal wound healing should involve four continuous and overlapping phases: Haemostasis, inflammation, proliferation, and remodelling .[4]

Figure.4 Wound Healing Stages

The process of the wound being closed by clotting.

• Happens very quickly.
• Starts when blood leaks out of the body, then blood vessels constrict to restrict the blood flow.
• The platelets aggregate and adhere to the sub-endothelium surface within seconds of the rupture of a blood vessel's epithelial wall.
• After that, the first fibrin strands begin to adhere in about sixty seconds.
• As the fibrin mesh begins, the blood is transformed from liquid to gel through pro-coagulants and the release of prothrombin.
• The formation of a thrombus or clot keeps the platelets and blood cells trapped in the wound area.
• The thrombus is generally important in the stages of wound healing but becomes a problem if it detaches from the vessel wall and goes through the circulatory system, possibly causing a stroke, pulmonary embolism or heart attack[5][3].

• Begins right after the injury when the injured blood vessels leak transudate (made of water, salt, and protein) causing localized swelling.
• Inflammation both controls bleeding and prevents infection.
• The fluid engorgement allows healing and repair cells to move to the site of the wound.
• During the inflammatory phase, damaged cells, pathogens, and bacteria are removed from the wound area.
• The white blood cells, growth factors, nutrients and enzymes create the swelling, heat, pain and redness commonly seen during this stage of wound healing.
• Inflammation is a natural part of the wound healing process and is only problematic if prolonged or excessive.

When the wound is rebuilt with new tissue made up of collagen and extracellular matrix

• The wound contracts as new tissues are built.
• A new network of blood vessels must be constructed so that the granulation tissue can be healthy and receive sufficient oxygen and nutrients.
• Myofibroblasts cause the wound to contract by gripping the wound edges and pulling them together using a mechanism similar to that of smooth muscle cells.
• In healthy stages of wound healing, granulation tissue is pink or red and uneven in texture. Healthy granulation tissue does not bleed easily.
• Dark granulation tissue can be a sign of infection, ischemia, or poor perfusion.
• Finally epithelial cells resurface the injury.
• Epithelialization happens faster when wounds are kept moist and hydrated.
• Generally, when occlusive or semi-occlusive dressings are applied within 48 hours after injury, they will maintain correct tissue humidity to optimize epithelialization.

Maturation Phase (Remodelling Stage)[edit | edit source]

• Collagen is remodelled from type III to type I and the wound fully closes.
• The cells that had been used to repair the wound but which are no longer needed are removed by apoptosis, or programmed cell death.
• The collagen laid down during the proliferative phase, it is disorganized and the wound is thick.
• Collagen is remodelled into a more organized structure along lines of stress, thereby increasing the tensile strength of the healing tissues. Fibroblasts secrete matrix metalloproteinases. The enzymes facilitate remodelling of type III collagen to type I collagen[4].
• Generally, remodelling begins about 21 days after an injury and can continue for a year or more.
• Even with cross-linking, healed wound areas continue to be weaker than uninjured skin, generally only having 80% of the tensile strength of unwounded skin[5].

Any disruption in wound healing phases leads to excessive wound healing or chronic wound formation.

• The pathogenesis of the excessive wound healing is not fully understood.
• An abnormal form of a wound healing that is characterized by a continuous localized inflammation.
• Excessive collagen synthesis, abnormal collagen turnover and exaggerated ECM accumulation in these wounds. e.g. "Keloid" and "hypertrophic scars".

Other Complications can include:

• Deficient scar formation.
• Exuberant granulation.
• Deficient contraction (in skin grafts) or excessive contraction (in burns).
• Others: Dystrophic calcification[6], pigmentary changes[7], painful scars, incisional hernia.[8]

Factors Affecting the Wound Healing[edit | edit source]

Also, consider

• Extrinsic factors which include: support surfaces, friction, and shear and effective repositioning schedules.
• Local factors: moisture (keeping a wound moist improves healing)[9]; edema; faulty technique of wound closure; Ischemia and necrosis; foreign bodies[10].

The most common wounds that are treated by wound care physical therapist are:[11]

• Stage III, IV or unstageable pressure ulcers.
• Diabetic wounds, see image.
• Chronic wounds.
• Venous and/or arterial wounds.
• Extremity wounds with oedema.
• Non-healing surgical wounds.

Physical therapy wound care begins with a comprehensive evaluation and the development of an individualized care plan. [11]

What stage wound has granulation tissue?

What stage of healing occurs after the formation of granulation tissue?

What step is granulation in tissue repair?

What is Stage 3 of wound healing?