Granulation tissue

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Granulation tissue is new connective tissue and microscopic blood vessels that form on the surfaces of a wound during the healing process. [1] Granulation tissue typically grows from the base of a wound and is able to fill wounds of almost any size. Examples of granulation tissue can be seen in pyogenic granulomas and pulp polyps. Its histological appearance is characterized by proliferation of fibroblasts and thin-walled, delicate capillaries (angiogenesis), and infiltrated inflammatory cells in a loose extracellular matrix.

Contents

Appearance

Example of granulation tissue from a cut on a finger with "proud flesh". Finger with granulation tissue.jpg
Example of granulation tissue from a cut on a finger with "proud flesh".

During the migratory phase of wound healing, granulation tissue is:

Structure

Granulation tissue is composed of tissue matrix supporting a variety of cell types, [3] most of which can be associated with one of the following functions:

An excess of granulation tissue (caro luxurians) is informally referred to as "proud flesh". [4]

Extracellular matrix

Histopathology of granulation tissue at 11 days after injury, showing fibroblasts, hemorrhage and lymphocytes. Histopathology of biopsy site at 11 days, high magnification.jpg
Histopathology of granulation tissue at 11 days after injury, showing fibroblasts, hemorrhage and lymphocytes.

The extracellular matrix of granulation tissue is created and modified by fibroblasts. [5] Initially, it consists of a network of type-III collagen, a weaker form of the structural protein that can be produced rapidly. This is later replaced by the stronger, long-stranded type-I collagen, as evidenced in scar tissue.

Immunity

The main immune cells active in the tissue are macrophages and neutrophils, although other leukocytes are also present. [6] These work to phagocytize old or damaged tissue, and protect the healing tissue from pathogenic infection. This is necessary both to aid the healing process and to protect against invading pathogens, as the wound often does not have an effective skin barrier to act as a first line of defense.

Vascularization

It is necessary for a network of blood vessels to be established as soon as possible to provide the growing tissue with nutrients, to take away cellular wastes, and transport new leukocytes to the area. Fibroblasts, the main cells that deposit granulation tissue, depend on oxygen to proliferate and lay down the new extracellular matrix. [7]

In vascularisation, also called angiogenesis, endothelial cells quickly grow into the tissue from older, intact blood vessels. [8] These branch out in a systematic way, forming anastomoses with other vessels.

Approximate times of the different phases of wound healing, with substantial variation depending on wound size and healing conditions. Granulation tissue formation is seen in green box at days to weeks. Wound healing phases.png
Approximate times of the different phases of wound healing, with substantial variation depending on wound size and healing conditions. Granulation tissue formation is seen in green box at days to weeks.

Related Research Articles

<span class="mw-page-title-main">Angiogenesis</span> Blood vessel formation, when new vessels emerge from existing vessels

Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature mainly by processes of sprouting and splitting, but processes such as coalescent angiogenesis, vessel elongation and vessel cooption also play a role. Vasculogenesis is the embryonic formation of endothelial cells from mesoderm cell precursors, and from neovascularization, although discussions are not always precise. The first vessels in the developing embryo form through vasculogenesis, after which angiogenesis is responsible for most, if not all, blood vessel growth during development and in disease.

<span class="mw-page-title-main">Fibronectin</span> Protein involved in cell adhesion, cell growth, cell migration and differentiation

Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collagen, fibrin, and heparan sulfate proteoglycans.

<span class="mw-page-title-main">Extracellular matrix</span> Network of proteins and molecules outside cells that provides structural support for cells

In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and biochemical support to surrounding cells. Because multicellularity evolved independently in different multicellular lineages, the composition of ECM varies between multicellular structures; however, cell adhesion, cell-to-cell communication and differentiation are common functions of the ECM.

<span class="mw-page-title-main">Connective tissue</span> Type of biological tissue in animals

Connective tissue is one of the four primary types of animal tissue, a group of cells that are similar in structure, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesoderm, the middle embryonic germ layer. Connective tissue is found in between other tissues everywhere in the body, including the nervous system. The three meninges, membranes that envelop the brain and spinal cord, are composed of connective tissue. Most types of connective tissue consists of three main components: elastic and collagen fibers, ground substance, and cells. Blood, and lymph are classed as specialized fluid connective tissues that do not contain fiber. All are immersed in the body water. The cells of connective tissue include fibroblasts, adipocytes, macrophages, mast cells and leukocytes.

<span class="mw-page-title-main">Healing</span> Process of the restoration of health

With physical trauma or disease suffered by an organism, healing involves the repairing of damaged tissue(s), organs and the biological system as a whole and resumption of (normal) functioning. Medicine includes the process by which the cells in the body regenerate and repair to reduce the size of a damaged or necrotic area and replace it with new living tissue. The replacement can happen in two ways: by regeneration in which the necrotic cells are replaced by new cells that form "like" tissue as was originally there; or by repair in which injured tissue is replaced with scar tissue. Most organs will heal using a mixture of both mechanisms.

<span class="mw-page-title-main">Wound healing</span> Series of events that restore integrity to damaged tissue after an injury

Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue.

<span class="mw-page-title-main">Fibrosis</span> Excess connective tissue in healing

Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of permanent scar tissue.

In cellular biology, haptotaxis is the directional motility or outgrowth of cells, e.g. in the case of axonal outgrowth, usually up a gradient of cellular adhesion sites or substrate-bound chemoattractants. These gradients are naturally present in the extracellular matrix (ECM) of the body during processes such as angiogenesis, or artificially present in biomaterials where gradients are established by altering the concentration of adhesion sites on a polymer substrate.

<span class="mw-page-title-main">Basement membrane</span> Thin fibrous layer between the cells and the adjacent connective tissue in animals

The basement membrane, also known as base membrane, is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between epithelial tissues including mesothelium and endothelium, and the underlying connective tissue.

Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any organ, for example in the uterine mucosa (endometrium), prostate, bone marrow, lymph node and the ovary. They are cells that support the function of the parenchymal cells of that organ. The most common stromal cells include fibroblasts and pericytes. The term stromal comes from Latin stromat-, "bed covering", and Ancient Greek στρῶμα, strôma, "bed".

<span class="mw-page-title-main">Interstitium</span> In anatomy, a fluid-filled space between a structural barrier and internal structures

The interstitium is a contiguous fluid-filled space existing between a structural barrier, such as a cell membrane or the skin, and internal structures, such as organs, including muscles and the circulatory system. The fluid in this space is called interstitial fluid, comprises water and solutes, and drains into the lymph system. The interstitial compartment is composed of connective and supporting tissues within the body – called the extracellular matrix – that are situated outside the blood and lymphatic vessels and the parenchyma of organs. The role of the interstitium in solute concentration, protein transport and hydrostatic pressure impacts human pathology and physiological responses such as edema, inflammation and shock.

A chronic wound is a wound that does not heal in an orderly set of stages and in a predictable amount of time the way most wounds do; wounds that do not heal within three months are often considered chronic. Chronic wounds seem to be detained in one or more of the phases of wound healing. For example, chronic wounds often remain in the inflammatory stage for too long. To overcome that stage and jump-start the healing process, a number of factors need to be addressed such as bacterial burden, necrotic tissue, and moisture balance of the whole wound. In acute wounds, there is a precise balance between production and degradation of molecules such as collagen; in chronic wounds this balance is lost and degradation plays too large a role.

<span class="mw-page-title-main">Myofibroblast</span> Cell type with functions of both muscular and fibrous connective tissue

A myofibroblast is a cell phenotype that was first described as being in a state between a fibroblast and a smooth muscle cell.

<span class="mw-page-title-main">Leukocyte extravasation</span> Movement of white blood cells out of blood vessels and towards the inflamed site

In immunology, leukocyte extravasation is the movement of leukocytes out of the circulatory system (extravasation) and towards the site of tissue damage or infection. This process forms part of the innate immune response, involving the recruitment of non-specific leukocytes. Monocytes also use this process in the absence of infection or tissue damage during their development into macrophages.

<span class="mw-page-title-main">Desmoplasia</span> Growth of fibrous or connective tissue

In medicine, desmoplasia is the growth of fibrous connective tissue. It is also called a desmoplastic reaction to emphasize that it is secondary to an insult. Desmoplasia may occur around a neoplasm, causing dense fibrosis around the tumor, or scar tissue (adhesions) within the abdomen after abdominal surgery.

Acellular dermis is a type of biomaterial derived from processing human or animal tissues to remove cells and retain portions of the extracellular matrix (ECM). These materials are typically cell-free, distinguishing them from classical allografts and xenografts, can be integrated or incorporated into the body, and have been FDA approved for human use for more than 10 years in a wide range of clinical indications.

<span class="mw-page-title-main">Tumor microenvironment</span> Surroundings of tumors including nearby cells and blood vessels

The tumor microenvironment is a complex ecosystem surrounding a tumor, composed of cancer cells, stromal tissue and the extracellular matrix. Mutual interaction between cancer cells and the different components of the tumor microenvironment support its growth and invasion in healthy tissues which correlates with tumor resistance to current treatments and poor prognosis. The tumor microenvironment is in constant change because of the tumor's ability to influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells.

<span class="mw-page-title-main">Diabetic foot ulcer</span> Medical condition

Diabetic foot ulcer is a breakdown of the skin and sometimes deeper tissues of the foot that leads to sore formation. It is thought to occur due to abnormal pressure or mechanical stress chronically applied to the foot, usually with concomitant predisposing conditions such as peripheral sensory neuropathy, peripheral motor neuropathy, autonomic neuropathy or peripheral arterial disease. It is a major complication of diabetes mellitus, and it is a type of diabetic foot disease. Secondary complications to the ulcer, such as infection of the skin or subcutaneous tissue, bone infection, gangrene or sepsis are possible, often leading to amputation.

A cancer-associated fibroblast (CAF) is a cell type within the tumor microenvironment that promotes tumorigenic features by initiating the remodelling of the extracellular matrix or by secreting cytokines. CAFs are a complex and abundant cell type within the tumour microenvironment; the number cannot decrease, as they are unable to undergo apoptosis.

<span class="mw-page-title-main">Dermal macrophage</span> Skin macrophages used for wound repair and hair growth

Dermal macrophages are macrophages in the skin that facilitate skin homeostasis by mediating wound repair, hair growth, and salt balance. Their functional role in these processes is the mediator of inflammation. They can acquire an M1 or M2 phenotype to promote or suppress an inflammatory response, thereby influencing other cells' activity via the production of pro-inflammatory or anti-inflammatory cytokines. Dermal macrophages' ability to acquire pro-inflammatory properties also potentiates them in cancer defence. M1 macrophages can suppress tumour growth in the skin by their pro-inflammatory properties. However, M2 macrophages support tumour growth and invasion by the production of Th2 cytokines such as TGFβ and IL-10. Thus, the exact contribution of each phenotype to cancer defence and the skin's homeostasis is still unclear.

References

  1. "Granulation Tissue Definition". Memidex. Archived from the original on 16 November 2018. Retrieved 25 October 2014.
  2. Bhat, Sriram (2013). Srb's Manual of Surgery, 4e. Jaypee Brother Medical Pub. p. 18. ISBN   9789350259443.
  3. Olczyk, Pawel; Mencner, Łukasz; Komosinska-Vassev, Katarzyna (2014). "The Role of the Extracellular Matrix Components in Cutaneous Wound Healing". BioMed Research International. 2014: 1–8. doi: 10.1155/2014/747584 . PMID   24772435.
  4. Healing and Repair Archived 2010-09-27 at the Wayback Machine Chapter 9 from an "Introduction to Pathology" on a Tuskegee University website
  5. Midwood, Kim S.; Williams, Leyla Valenick; Schwarzbauer, Jean E. (June 2004). "Tissue repair and the dynamics of the extracellular matrix". The International Journal of Biochemistry & Cell Biology. 36 (6): 1031–1037. doi:10.1016/j.biocel.2003.12.003. PMID   15094118.
  6. Sindrilaru, A; Scharffetter-Kochanek, K (September 2013). "Disclosure of the Culprits: Macrophages-Versatile Regulators of Wound Healing". Advances in Wound Care. 2 (7): 357–368. doi:10.1089/wound.2012.0407. PMC   3842885 . PMID   24587973.
  7. Cialdai, Francesca; Risaliti, Chiara; Monici, Monica (4 October 2022). "Role of fibroblasts in wound healing and tissue remodeling on Earth and in space". Frontiers in Bioengineering and Biotechnology. 10. doi: 10.3389/fbioe.2022.958381 . PMC   9578548 . PMID   36267456.
  8. Tonnesen, Marcia G.; Feng, Xiaodong; Clark, Richard A.F. (December 2000). "Angiogenesis in Wound Healing". Journal of Investigative Dermatology Symposium Proceedings. 5 (1): 40–46. doi:10.1046/j.1087-0024.2000.00014.x. PMID   11147674.