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You are watching: The granulations that appear during the healing of a large, open wound are composed mainly of

StatPearls . Treacertain Island (FL): StatPearls Publishing; 2021 Jan-.



Granulation tissue is a crucial component in the wound healing process. Wounds deserve to heal by primary intention (wound edges approximate easily) and secondary intention (wounds edges do not approximate). Granulation tissue matrix will fill wounds that heal by second intention. This tworry type is likewise present in chronic wounds that have actually many kind of various causes. This short article will comment on the device of wound healing and also repair, the function that granulation tissue plays in that procedure, the pathophysiology resulting in chronic wounds and persistent granulation tworry, and also the clinical significance of granulation tissue. 


Granulation tproblem is thought about a contractile organ, defined histologically by the existence and also proliferation of fibroblasts, keratinocytes, endothelial cells, new thin-walled capillaries, and also inflammatory cell infiltration of the extracellular matrix. The formation of granulation tproblem is complicated and calls for an detailed interplay in between the cell forms at the wound site.


This cell form is responsible for the development of the granulation tworry extracellular matrix (ECM). The ECM initially consists of kind III collagen, which is a rapidly developed and a weaker form of collagen that is eventually reinserted by the more powerful type I collagen at the finish of wound healing and sauto development. TGF-β is a growth aspect produced by both fibroblasts and also keratinocytes during the wound healing process and has been shown to induce granulation tproblem development and also the differentiation of myofibroblasts.


The keratinocytes are responsible for re-epithelialization of the epidermis after injury. The ability of the keratinocytes to distinguish and also prolifeprice relies on the stem cell population at the wound site and also stimulation by assorted cytokines and expansion determinants (epidermal growth element, TGF-α & KGF: keratinocyte expansion factor). The cell to cell binding in between keratinocytes is looser in the time of the wound healing process and becomes stronger by its completion. Immediately after injury, the keratinocytes nearby to the wound undergo an activation procedure that transforms gene expression and also promotes their migration over the bed of the wound.

In an autocrine and also paracrine fashion, keratinocytes create signals that manage even more keratinocyte activation and stimulate other cell kinds (fibroblasts) in the time of wound closure. IL-1 boosts keratinocyte migration and proliferation, activate adjacent fibroblasts, boosts KGF (keratinocyte growth factor). TNF-α acts similarly to IL-1 and activates the FGF (fibroblast growth factor) pathmeans. TGF-β, produced by keratinocytes and fibroblasts, acts to revert keratinocytes to their basal cell phenotype. This signaling process is deficient in venous ulcers and also contributes to non-healing.

Endothelial Cells

The endothelial cells are responsible for revascularization/angiogenesis at the website of the wound. Initially quiescent, the resident endothelial cells come to be set off by numerous angiogenic components, consisting of fibroblast expansion element, vascular endothelial growth element (VEGF), platelet-acquired expansion aspect (PDGF), angiogenin, and also transcreating growth components α & β (TGFα & TGFβ). Once triggered, the endothelial cells undergo four occasions in the formation of brand-new blood vessels:

Angiogenesis needs that the endothelial cells thrive easily into the brand-new tissue from the older intact blood vessels that branch out and develop anastomoses through various other vessels and also restoring blood flow. This process is crucial for the restoration of the flow of nutrients and oxygen to the site, removing waste, and also transportation of leukocytes to the site. Without this, granulation tproblem development would be stunted and also wound healing expanded.


Myofibroblasts are responsible for the contractile process in wound clocertain. When granulation tworry is forming, fibroblasts slowly modulate right into myofibroblasts, identified by bundles of actin microfilaments along their cell"s plasma membrane. Prostaglandins, bradykinins, epinephrine, and also norepinephrine modulate the attribute of contraction by the myofibroblasts. Ultimately, the actin binds to the extracellular component fibronectin, attaches to the collagen fibers, retracts, and also draws collagen fibers toward it. The mass result causes wound contraction and also closure.

Immune Cells

Neutrophils (initially to the wound) and macrophperiods are the main immune cells at the site of wounds that aid in wound healing and also defend versus invading pathogens. Both cell types are phagocytic, definition that they engulf and ingest pathogens, debris, and also damaged tconcern, enabling for defense and healing.<1><2><3>


Granulation tissue is a form of brand-new connective tworry, and also microscopic blood vessels have actually three major features.


During this phase of wound healing, the blood vessels at the site of injury contract, and the blood that leaked out through the wounds start to coagulate and scab over. The coagulation procedure outcomes from the aggregation of thrombocytes, forming a fibrin netoccupational. The fibrin netoccupational is the basis for a clot and serves as a short-term matrix for migrating cells. The thrombocytes release cytokines and also expansion components that serve as pro-inflammatory signals to entice the immune response to the site of the wound.

Inflammatory Stage

This phase begins as soon as neutrophils begin to arrive at the wound website. Neutrophils arrive at the wound within a couple of minutes and also proceed to accumulate for numerous days. The neutrophils" role is to entrap the microorganisms current at the wound website from the start of the injury. The neutrophils likewise amplify the pro-inflammatory response and release their very own markers.

Monocytes arrive at the site of injury within two days, wright here they distinguish into macrophperiods. The function of macrophperiods is to phagocytose debris, pathogens, and neutrophils while likewise creating chemical mediators (TGF-beta and VEGF) that serve to recruit fibroblasts and endothelial cells that mark the following stage of healing. Throughout this phase, the site of injury becomes erythematous and edematous. This phase takes about 72 hrs to complete.

Proliferative Stage

During this stage of healing, re-epithelialization and also the replacement of the clot by granulation tconcern occurs all at once. This phase is very cellular with the major cell kinds, including fibroblasts, keratinocytes, and also endothelial cells. Fibroblasts function to synthesize collagen and the extracellular matrix. The granulation tworry itself is consisted of of extracellular matrix, proteoglycans, hyaluronic acid, collagen, and also elastin. Cytokines and also development determinants, interleukins, and angiogenesis factors are energetic during this time, which have the right to proceed all over from days to weeks under normal scenarios. Granulation tworry grows from the base of the wound and also have the right to frequently fill any kind of dimension wound. Any errors in the development of granulation tworry can cause chronic wound development. Fopower bodies at the website of a wound have the right to likewise lead to persistent granulation tconcern and also negative wound healing via excess macropheras, fibroblasts, and also capillaries reacting around the foreign product.

Remodeling Stage

The last stage of wound healing involves apoptosis and also the manufacturing of new cells. The apoptosis and destruction of the extracellular matrix and also immature form III collagen and also the ultimate development of mature kind I collagen are critical to scar formation, integrity, and toughness. This phase can proceed from months to years. If tbelow are errors throughout this phase, there might be too much wound healing bring about hypertrophic or keloidal scarring or a chronic wound resulting in persistent granulation tworry.  

Healthy granulation tconcern appears pink to red as a result of brand-new capillary formation, is soft to the touch, moist appears “bumpy,” and commonly painless. Unhealthy granulation tissue is darker red, bleeds quickly through minimal contact, painful, and also probably extended by shiny white or yellow fibrous tconcern that is avascular, impeding healing. When granulation tworry appears “unhealthy,” an infectious procedure or poor healing need to be suspected. Wound culture and appropriate treatment according to the society results should be completed as soon as feasible. Once the infection is ruled out or cleared, some chronic wounds may respond to basic cautery through silver nitrate or via topical steroid preparations, while those through the overlying fibrous tworry will certainly need debridement via a curette or scalpel to allow for healing.<1><2><3><4><5><6><7>


Wound healing deserve to become prolonged under numerous circumstances. The pathophysiology of wound healing, bring about excess and also unhealthy and balanced granulation tconcern and chronic wounds are complex. The causes might include infection at the website of the wound bring about extreme recruitment of inflammatory cells. Infections lead to raised release of reactive oxygen species that are damaging to the tworry and can additionally cause the development of biomovies, which add to bad wound healing and are brought about by bacterial toxins. Infections deserve to cause further complications, including abscess, cellulitis, osteomyelitis, and also loss of limbs. 

Necrosis, negative perfusion, and negative nutrition/metabolism because of inadequate blood supply due to the trauma itself, poor angiogenesis, and underlying problems (diabetes and vascular insufficiency) are also resources of chronic wounds and also persistent granulation tworry.

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Clinical Significance

Granulation tproblem might persist under several situations resulting from underlying conditions and/or errors in the steras of wound healing (errors in the proliferative phase and also remodeling phase).<1><2><3><4><6><9><8>