Wound healing

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Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue. Wound healing_sentence_0

In this article, which focuses on humans, wound healing is depicted in a discrete timeline of physical attributes (phases) constituting the post-trauma repairing process. Wound healing_sentence_1

In undamaged skin, the epidermis (surface layer) and dermis (deeper layer) form a protective barrier against the external environment. Wound healing_sentence_2

When the barrier is broken, a regulated sequence of biochemical events is set into motion to repair the damage. Wound healing_sentence_3

This process is divided into predictable phases: blood clotting (hemostasis), inflammation, tissue growth (cell proliferation), and tissue remodeling (maturation and cell differentiation). Wound healing_sentence_4

Blood clotting may be considered to be part of the inflammation stage instead of a separate stage. Wound healing_sentence_5

The wound healing process is not only complex but also fragile, and it is susceptible to interruption or failure leading to the formation of non-healing chronic wounds. Wound healing_sentence_6

Factors that contribute to non-healing chronic wounds are diabetes, venous or arterial disease, infection, and metabolic deficiencies of old age. Wound healing_sentence_7

Wound care encourages and speeds wound healing via cleaning and protection from reinjury or infection. Wound healing_sentence_8

Depending on each patient's needs, it can range from the simplest first aid to entire nursing specialties such as wound, ostomy, and continence nursing and burn center care. Wound healing_sentence_9

Stages Wound healing_section_0

Wound healing_unordered_list_0

  • Hemostasis (blood clotting): Within the first few minutes of injury, platelets in the blood begin to stick to the injured site. They change into an amorphous shape, more suitable for clotting, and they release chemical signals to promote clotting. This results in the activation of fibrin, which forms a mesh and acts as "glue" to bind platelets to each other. This makes a clot that serves to plug the break in the blood vessel, slowing/preventing further bleeding.Wound healing_item_0_0
  • Inflammation: During this phase, damaged and dead cells are cleared out, along with bacteria and other pathogens or debris. This happens through the process of phagocytosis, where white blood cells engulf debris and destroy it. Platelet-derived growth factors are released into the wound that cause the migration and division of cells during the proliferative phase.Wound healing_item_0_1
  • Proliferation (growth of new tissue): In this phase, angiogenesis, collagen deposition, granulation tissue formation, epithelialization, and wound contraction occur. In angiogenesis, vascular endothelial cells form new blood vessels. In fibroplasia and granulation tissue formation, fibroblasts grow and form a new, provisional extracellular matrix (ECM) by excreting collagen and fibronectin. Concurrently, re-epithelialization of the epidermis occurs, in which epithelial cells proliferate and 'crawl' atop the wound bed, providing cover for the new tissue. In wound contraction, myofibroblasts decrease the size of the wound by gripping the wound edges and contracting using a mechanism that resembles that in smooth muscle cells. When the cells' roles are close to complete, unneeded cells undergo apoptosis.Wound healing_item_0_2
  • Maturation (remodeling): During maturation and remodeling, collagen is realigned along tension lines, and cells that are no longer needed are removed by programmed cell death, or apoptosis.Wound healing_item_0_3

Timing and re-epithelialization Wound healing_section_1

Timing is important to wound healing. Wound healing_sentence_10

Critically, the timing of wound re-epithelialization can decide the outcome of the healing. Wound healing_sentence_11

If the epithelization of tissue over a denuded area is slow, a scar will form over many weeks, or months; If the epithelization of a wounded area is fast, the healing will result in regeneration. Wound healing_sentence_12

Early vs cellular phase Wound healing_section_2

Wound healing is classically divided into hemostasis, inflammation, proliferation, and remodeling. Wound healing_sentence_13

Although a useful construct, this model employs considerable overlapping among individual phases. Wound healing_sentence_14

A complementary model has recently been described where the many elements of wound healing are more clearly delineated. Wound healing_sentence_15

The importance of this new model becomes more apparent through its utility in the fields of regenerative medicine and tissue engineering (see Research and development section below). Wound healing_sentence_16

In this construct, the process of wound healing is divided into two major phases: the early phase and the cellular phase: Wound healing_sentence_17

The early phase, which begins immediately following skin injury, involves cascading molecular and cellular events leading to hemostasis and formation of an early, makeshift extracellular matrix that provides structural staging for cellular attachment and subsequent cellular proliferation. Wound healing_sentence_18

The cellular phase involves several types of cells working together to mount an inflammatory response, synthesize granulation tissue, and restore the epithelial layer. Wound healing_sentence_19

Subdivisions of the cellular phase are: Wound healing_sentence_20

Wound healing_ordered_list_1

  1. Macrophages and inflammatory components (within 1–2 days)Wound healing_item_1_4
  2. Epithelial-mesenchymal interaction: re-epithelialization (phenotype change within hours, migration begins on day 1 or 2)Wound healing_item_1_5
  3. Fibroblasts and myofibroblasts: progressive alignment, collagen production, and matrix contraction (between day 4 and day 14)Wound healing_item_1_6
  4. Endothelial cells and angiogenesis (begins on day 4)Wound healing_item_1_7
  5. Dermal matrix: elements of fabrication (begins on day 4, lasting 2 weeks) and alteration/remodeling (begins after week 2, lasting weeks to months—depending on wound size).Wound healing_item_1_8

Inflammatory phase Wound healing_section_3

Just before the inflammatory phase is initiated, the clotting cascade occurs in order to achieve hemostasis, or stop blood loss by way of a fibrin clot. Wound healing_sentence_21

Thereafter, various soluble factors (including chemokines and cytokines) are released to attract cells that phagocytise debris, bacteria, and damaged tissue, in addition to releasing signaling molecules that initiate the proliferative phase of wound healing. Wound healing_sentence_22

Clotting cascade Wound healing_section_4

Main article: Coagulation Wound healing_sentence_23

When tissue is first wounded, blood comes in contact with collagen, triggering blood platelets to begin secreting inflammatory factors. Wound healing_sentence_24

Platelets also express sticky glycoproteins on their cell membranes that allow them to aggregate, forming a mass. Wound healing_sentence_25

Fibrin and fibronectin cross-link together and form a plug that traps proteins and particles and prevents further blood loss. Wound healing_sentence_26

This fibrin-fibronectin plug is also the main structural support for the wound until collagen is deposited. Wound healing_sentence_27

Migratory cells use this plug as a matrix to crawl across, and platelets adhere to it and secrete factors. Wound healing_sentence_28

The clot is eventually lysed and replaced with granulation tissue and then later with collagen. Wound healing_sentence_29

Platelets, the cells present in the highest numbers shortly after a wound occurs, release mediators into the blood, including cytokines and growth factors. Wound healing_sentence_30

Growth factors stimulate cells to speed their rate of division. Wound healing_sentence_31

Platelets release other proinflammatory factors like serotonin, bradykinin, prostaglandins, prostacyclins, thromboxane, and histamine, which serve several purposes, including increasing cell proliferation and migration to the area and causing blood vessels to become dilated and porous. Wound healing_sentence_32

In many ways, extravasated platelets in trauma perform a similar function to tissue macrophages and mast cells exposed to microbial molecular signatures in infection: they become activated, and secrete molecular mediators – vasoactive amines, eicosanoids, and cytokines – that initiate the inflammatory process. Wound healing_sentence_33

Vasoconstriction and vasodilation Wound healing_section_5

Immediately after a blood vessel is breached, ruptured cell membranes release inflammatory factors like thromboxanes and prostaglandins that cause the vessel to spasm to prevent blood loss and to collect inflammatory cells and factors in the area. Wound healing_sentence_34

This vasoconstriction lasts five to ten minutes and is followed by vasodilation, a widening of blood vessels, which peaks at about 20 minutes post-wounding. Wound healing_sentence_35

Vasodilation is the end result of factors released by platelets and other cells. Wound healing_sentence_36

The main factor involved in causing vasodilation is histamine. Wound healing_sentence_37

Histamine also causes blood vessels to become porous, allowing the tissue to become edematous because proteins from the bloodstream leak into the extravascular space, which increases its osmolar load and draws water into the area. Wound healing_sentence_38

Increased porosity of blood vessels also facilitates the entry of inflammatory cells like leukocytes into the wound site from the bloodstream. Wound healing_sentence_39

Polymorphonuclear neutrophils Wound healing_section_6

Within an hour of wounding, polymorphonuclear neutrophils (PMNs) arrive at the wound site and become the predominant cells in the wound for the first two days after the injury occurs, with especially high numbers on the second day. Wound healing_sentence_40

They are attracted to the site by fibronectin, growth factors, and substances such as kinins. Wound healing_sentence_41

Neutrophils phagocytise debris and kill bacteria by releasing free radicals in what is called a 'respiratory burst. Wound healing_sentence_42

They also cleanse the wound by secreting proteases that break down damaged tissue. Wound healing_sentence_43

Functional neutrophils at the wound site only have life-spans of around 2 days, so they usually undergo apoptosis once they have completed their tasks and are engulfed and degraded by macrophages. Wound healing_sentence_44

Other leukocytes to enter the area include helper T cells, which secrete cytokines to cause more T cells to divide and to increase inflammation and enhance vasodilation and vessel permeability. Wound healing_sentence_45

T cells also increase the activity of macrophages. Wound healing_sentence_46

Macrophages Wound healing_section_7

One of the macrophage's roles is to phagocytize other expended phagocytes, bacteria and damaged tissue, and they also debride damaged tissue by releasing proteases. Wound healing_sentence_47

Macrophages function in regeneration and are essential for wound healing. Wound healing_sentence_48

They are stimulated by the low oxygen content of their surroundings to produce factors that induce and speed angiogenesis and they also stimulate cells that reepithelialize the wound, create granulation tissue, and lay down a new extracellular matrix. Wound healing_sentence_49

By secreting these factors, macrophages contribute to pushing the wound healing process into the next phase. Wound healing_sentence_50

They replace PMNs as the predominant cells in the wound by two days after injury. Wound healing_sentence_51

The spleen contains half the body's monocytes in reserve ready to be deployed to injured tissue. Wound healing_sentence_52

Attracted to the wound site by growth factors released by platelets and other cells, monocytes from the bloodstream enter the area through blood vessel walls. Wound healing_sentence_53

Numbers of monocytes in the wound peak one to one and a half days after the injury occurs. Wound healing_sentence_54

Once they are in the wound site, monocytes mature into macrophages. Wound healing_sentence_55

Macrophages also secrete a number of factors such as growth factors and other cytokines, especially during the third and fourth post-wounding days. Wound healing_sentence_56

These factors attract cells involved in the proliferation stage of healing to the area. Wound healing_sentence_57

In wound healing that result in incomplete repair, scar contraction occurs, bringing varying gradations of structural imperfections, deformities and problems with flexibility. Wound healing_sentence_58

Macrophages may restrain the contraction phase. Wound healing_sentence_59

Scientists have reported that removing the macrophages from a salamander resulted in failure of a typical regeneration response (limb regeneration), instead bringing on a repair (scarring) response. Wound healing_sentence_60

Decline of inflammatory phase Wound healing_section_8

As inflammation dies down, fewer inflammatory factors are secreted, existing ones are broken down, and numbers of neutrophils and macrophages are reduced at the wound site. Wound healing_sentence_61

These changes indicate that the inflammatory phase is ending and the proliferative phase is underway. Wound healing_sentence_62

In vitro evidence, obtained using the dermal equivalent model, suggests that the presence of macrophages actually delays wound contraction and thus the disappearance of macrophages from the wound may be essential for subsequent phases to occur. Wound healing_sentence_63

Because inflammation plays roles in fighting infection, clearing debris and inducing the proliferation phase, it is a necessary part of healing. Wound healing_sentence_64

However, inflammation can lead to tissue damage if it lasts too long. Wound healing_sentence_65

Thus the reduction of inflammation is frequently a goal in therapeutic settings. Wound healing_sentence_66

Inflammation lasts as long as there is debris in the wound. Wound healing_sentence_67

Thus, if the individual's immune system is compromised and is unable to clear the debris from the wound and/or if excessive detritus, devitalized tissue, or microbial biofilm is present in the wound, these factors may cause a prolonged inflammatory phase and prevent the wound from properly commencing the proliferation phase of healing. Wound healing_sentence_68

This can lead to a chronic wound. Wound healing_sentence_69

Proliferative phase Wound healing_section_9

About two or three days after the wound occurs, fibroblasts begin to enter the wound site, marking the onset of the proliferative phase even before the inflammatory phase has ended. Wound healing_sentence_70

As in the other phases of wound healing, steps in the proliferative phase do not occur in a series but rather partially overlap in time. Wound healing_sentence_71

Angiogenesis Wound healing_section_10

Further information: Angiogenesis Wound healing_sentence_72

Also called neovascularization, the process of angiogenesis occurs concurrently with fibroblast proliferation when endothelial cells migrate to the area of the wound. Wound healing_sentence_73

Because the activity of fibroblasts and epithelial cells requires oxygen and nutrients, angiogenesis is imperative for other stages in wound healing, like epidermal and fibroblast migration. Wound healing_sentence_74

The tissue in which angiogenesis has occurred typically looks red (is erythematous) due to the presence of capillaries. Wound healing_sentence_75

Angiogenesis occurs in overlapping phases in response to inflammation: Wound healing_sentence_76

Wound healing_ordered_list_2

  1. Latent period: During the haemostatic and inflammatory phase of the wound healing process, vasodilation and permeabilisation allow leukocyte extravasation and phagocytic debridement and decontamination of the wound area. Tissue swelling aids later angiogenesis by expanding and loosening the existing collagenous extracellular matrix.Wound healing_item_2_9
  2. Endothelial activation: As the wound macrophages switches from inflammatory to healing mode, it begins to secrete endothelial chemotactic and growth factors to attract adjacent endothelial cells. Activated endothelial cells respond by retracting and reducing cell junctions, loosening themselves from their embedded endothelium. Characteristically the activated endothelial cells show enlarged nucleoli.Wound healing_item_2_10
  3. Degradation of endothelial basement membrane: The wound macrophages, mast cells and the endothelial cells themselves secrete proteases to break down existing vascular basal lamina.Wound healing_item_2_11
  4. Vascular sprouting: With the breakdown of endothelial basement membrane, detached endothelial cells from pre-existing capillaries and post-capillary venules can divide and migrate chemotactically towards the wound, laying down new vessels in the process. Vascular sprouting can be aided by ambient hypoxia and acidosis in the wound environment, as hypoxia stimulates the endothelial transcription factor, hypoxia inducible factor (HIF) to transactivate angiogenic genes such as VEGF and GLUT1. Sprouted vessels can self-organise into luminal morphologies, and fusion of blind channels give rise to new capillary networks.Wound healing_item_2_12
  5. Vascular maturation: the endothelium of vessels mature by laying down new endothelial extracellular matrix, followed by basal lamina formation. Lastly the vessel establishes a pericyte layer.Wound healing_item_2_13

Stem cells of endothelial cells, originating from parts of uninjured blood vessels, develop pseudopodia and push through the ECM into the wound site to establish new blood vessels. Wound healing_sentence_77

Endothelial cells are attracted to the wound area by fibronectin found on the fibrin scab and chemotactically by angiogenic factors released by other cells, e.g. from macrophages and platelets when in a low-oxygen environment. Wound healing_sentence_78

Endothelial growth and proliferation is also directly stimulated by hypoxia, and presence of lactic acid in the wound. Wound healing_sentence_79

For example, hypoxia stimulates the endothelial transcription factor, hypoxia-inducible factor (HIF) to transactivate a set of proliferative genes including vascular endothelial growth factor (VEGF) and glucose transporter 1 (GLUT1). Wound healing_sentence_80

To migrate, endothelial cells need collagenases and plasminogen activator to degrade the clot and part of the ECM. Wound healing_sentence_81

Zinc-dependent metalloproteinases digest basement membrane and ECM to allow cell migration, proliferation and angiogenesis. Wound healing_sentence_82

When macrophages and other growth factor-producing cells are no longer in a hypoxic, lactic acid-filled environment, they stop producing angiogenic factors. Wound healing_sentence_83

Thus, when tissue is adequately perfused, migration and proliferation of endothelial cells is reduced. Wound healing_sentence_84

Eventually blood vessels that are no longer needed die by apoptosis. Wound healing_sentence_85

Fibroplasia and granulation tissue formation Wound healing_section_11

Simultaneously with angiogenesis, fibroblasts begin accumulating in the wound site. Wound healing_sentence_86

Fibroblasts begin entering the wound site two to five days after wounding as the inflammatory phase is ending, and their numbers peak at one to two weeks post-wounding. Wound healing_sentence_87

By the end of the first week, fibroblasts are the main cells in the wound. Wound healing_sentence_88

Fibroplasia ends two to four weeks after wounding. Wound healing_sentence_89

As a model the mechanism of fibroplasia may be conceptualised as an analogous process to angiogenesis (see above) - only the cell type involved is fibroblasts rather than endothelial cells. Wound healing_sentence_90

Initially there is a latent phase where the wound undergoes plasma exudation, inflammatory decontamination and debridement. Wound healing_sentence_91

Oedema increases the wound histologic accessibility for later fibroplastic migration. Wound healing_sentence_92

Second, as inflammation nears completion, macrophage and mast cells release fibroblast growth and chemotactic factors to activate fibroblasts from adjacent tissue. Wound healing_sentence_93

Fibroblasts at this stage loosen themselves from surrounding cells and ECM. Wound healing_sentence_94

Phagocytes further release proteases that break down the ECM of neighbouring tissue, freeing the activated fibroblasts to proliferate and migrate towards the wound. Wound healing_sentence_95

The difference between vascular sprouting and fibroblast proliferation is that the former is enhanced by hypoxia, whilst the latter is inhibited by hypoxia. Wound healing_sentence_96

The deposited fibroblastic connective tissue matures by secreting ECM into the extracellular space, forming granulation tissue (see below). Wound healing_sentence_97

Lastly collagen is deposited into the ECM. Wound healing_sentence_98

In the first two or three days after injury, fibroblasts mainly migrate and proliferate, while later, they are the main cells that lay down the collagen matrix in the wound site. Wound healing_sentence_99

Origins of these fibroblasts are thought to be from the adjacent uninjured cutaneous tissue (although new evidence suggests that some are derived from blood-borne, circulating adult stem cells/precursors). Wound healing_sentence_100

Initially fibroblasts utilize the fibrin cross-linking fibers (well-formed by the end of the inflammatory phase) to migrate across the wound, subsequently adhering to fibronectin. Wound healing_sentence_101

Fibroblasts then deposit ground substance into the wound bed, and later collagen, which they can adhere to for migration. Wound healing_sentence_102

Granulation tissue functions as rudimentary tissue, and begins to appear in the wound already during the inflammatory phase, two to five days post wounding, and continues growing until the wound bed is covered. Wound healing_sentence_103

Granulation tissue consists of new blood vessels, fibroblasts, inflammatory cells, endothelial cells, myofibroblasts, and the components of a new, provisional extracellular matrix (ECM). Wound healing_sentence_104

The provisional ECM is different in composition from the ECM in normal tissue and its components originate from fibroblasts. Wound healing_sentence_105

Such components include fibronectin, collagen, glycosaminoglycans, elastin, glycoproteins and proteoglycans. Wound healing_sentence_106

Its main components are fibronectin and hyaluronan, which create a very hydrated matrix and facilitate cell migration. Wound healing_sentence_107

Later this provisional matrix is replaced with an ECM that more closely resembles that found in non-injured tissue. Wound healing_sentence_108

Growth factors (PDGF, TGF-β) and fibronectin encourage proliferation, migration to the wound bed, and production of ECM molecules by fibroblasts. Wound healing_sentence_109

Fibroblasts also secrete growth factors that attract epithelial cells to the wound site. Wound healing_sentence_110

Hypoxia also contributes to fibroblast proliferation and excretion of growth factors, though too little oxygen will inhibit their growth and deposition of ECM components, and can lead to excessive, fibrotic scarring. Wound healing_sentence_111

Collagen deposition Wound healing_section_12

One of fibroblasts' most important duties is the production of collagen. Wound healing_sentence_112

Collagen deposition is important because it increases the strength of the wound; before it is laid down, the only thing holding the wound closed is the fibrin-fibronectin clot, which does not provide much resistance to traumatic injury. Wound healing_sentence_113

Also, cells involved in inflammation, angiogenesis, and connective tissue construction attach to, grow and differentiate on the collagen matrix laid down by fibroblasts. Wound healing_sentence_114

Type III collagen and fibronectin generally begin to be produced in appreciable amounts at somewhere between approximately 10 hours and 3 days, depending mainly on wound size. Wound healing_sentence_115

Their deposition peaks at one to three weeks. Wound healing_sentence_116

They are the predominating tensile substances until the later phase of maturation, in which they are replaced by the stronger type I collagen. Wound healing_sentence_117

Even as fibroblasts are producing new collagen, collagenases and other factors degrade it. Wound healing_sentence_118

Shortly after wounding, synthesis exceeds degradation so collagen levels in the wound rise, but later production and degradation become equal so there is no net collagen gain. Wound healing_sentence_119

This homeostasis signals the onset of the later maturation phase. Wound healing_sentence_120

Granulation gradually ceases and fibroblasts decrease in number in the wound once their work is done. Wound healing_sentence_121

At the end of the granulation phase, fibroblasts begin to commit apoptosis, converting granulation tissue from an environment rich in cells to one that consists mainly of collagen. Wound healing_sentence_122

Epithelialization Wound healing_section_13

The formation of granulation tissue into an open wound allows the reepithelialization phase to take place, as epithelial cells migrate across the new tissue to form a barrier between the wound and the environment. Wound healing_sentence_123

Basal keratinocytes from the wound edges and dermal appendages such as hair follicles, sweat glands and sebacious (oil) glands are the main cells responsible for the epithelialization phase of wound healing. Wound healing_sentence_124

They advance in a sheet across the wound site and proliferate at its edges, ceasing movement when they meet in the middle. Wound healing_sentence_125

In healing that results in a scar, sweat glands, hair follicles and nerves do not form. Wound healing_sentence_126

With the lack of hair follicles, nerves and sweat glands, the wound, and the resulting healing scar, provide a challenge to the body with regards to temperature control. Wound healing_sentence_127

Keratinocytes migrate without first proliferating. Wound healing_sentence_128

Migration can begin as early as a few hours after wounding. Wound healing_sentence_129

However, epithelial cells require viable tissue to migrate across, so if the wound is deep it must first be filled with granulation tissue. Wound healing_sentence_130

Thus the time of onset of migration is variable and may occur about one day after wounding. Wound healing_sentence_131

Cells on the wound margins proliferate on the second and third day post-wounding in order to provide more cells for migration. Wound healing_sentence_132

If the basement membrane is not breached, epithelial cells are replaced within three days by division and upward migration of cells in the stratum basale in the same fashion that occurs in uninjured skin. Wound healing_sentence_133

However, if the basement membrane is ruined at the wound site, reepithelization must occur from the wound margins and from skin appendages such as hair follicles and sweat and oil glands that enter the dermis that are lined with viable keratinocytes. Wound healing_sentence_134

If the wound is very deep, skin appendages may also be ruined and migration can only occur from wound edges. Wound healing_sentence_135

Migration of keratinocytes over the wound site is stimulated by lack of contact inhibition and by chemicals such as nitric oxide. Wound healing_sentence_136

Before they begin to migrate, cells must dissolve their desmosomes and hemidesmosomes, which normally anchor the cells by intermediate filaments in their cytoskeleton to other cells and to the ECM. Wound healing_sentence_137

Transmembrane receptor proteins called integrins, which are made of glycoproteins and normally anchor the cell to the basement membrane by its cytoskeleton, are released from the cell's intermediate filaments and relocate to actin filaments to serve as attachments to the ECM for pseudopodia during migration. Wound healing_sentence_138

Thus keratinocytes detach from the basement membrane and are able to enter the wound bed. Wound healing_sentence_139

Before they begin migrating, keratinocytes change shape, becoming longer and flatter and extending cellular processes like lamellipodia and wide processes that look like ruffles. Wound healing_sentence_140

Actin filaments and pseudopodia form. Wound healing_sentence_141

During migration, integrins on the pseudopod attach to the ECM, and the actin filaments in the projection pull the cell along. Wound healing_sentence_142

The interaction with molecules in the ECM through integrins further promotes the formation of actin filaments, lamellipodia, and filopodia. Wound healing_sentence_143

Epithelial cells climb over one another in order to migrate. Wound healing_sentence_144

This growing sheet of epithelial cells is often called the epithelial tongue. Wound healing_sentence_145

The first cells to attach to the basement membrane form the stratum basale. Wound healing_sentence_146

These basal cells continue to migrate across the wound bed, and epithelial cells above them slide along as well. Wound healing_sentence_147

The more quickly this migration occurs, the less of a scar there will be. Wound healing_sentence_148

Fibrin, collagen, and fibronectin in the ECM may further signal cells to divide and migrate. Wound healing_sentence_149

Like fibroblasts, migrating keratinocytes use the fibronectin cross-linked with fibrin that was deposited in inflammation as an attachment site to crawl across. Wound healing_sentence_150

As keratinocytes migrate, they move over granulation tissue but stay underneath the scab, thereby separating the scab from the underlying tissue. Wound healing_sentence_151

Epithelial cells have the ability to phagocytize debris such as dead tissue and bacterial matter that would otherwise obstruct their path. Wound healing_sentence_152

Because they must dissolve any scab that forms, keratinocyte migration is best enhanced by a moist environment, since a dry one leads to formation of a bigger, tougher scab. Wound healing_sentence_153

To make their way along the tissue, keratinocytes must dissolve the clot, debris, and parts of the ECM in order to get through. Wound healing_sentence_154

They secrete plasminogen activator, which activates plasminogen, turning it into plasmin to dissolve the scab. Wound healing_sentence_155

Cells can only migrate over living tissue, so they must excrete collagenases and proteases like matrix metalloproteinases (MMPs) to dissolve damaged parts of the ECM in their way, particularly at the front of the migrating sheet. Wound healing_sentence_156

Keratinocytes also dissolve the basement membrane, using instead the new ECM laid down by fibroblasts to crawl across. Wound healing_sentence_157

As keratinocytes continue migrating, new epithelial cells must be formed at the wound edges to replace them and to provide more cells for the advancing sheet. Wound healing_sentence_158

Proliferation behind migrating keratinocytes normally begins a few days after wounding and occurs at a rate that is 17 times higher in this stage of epithelialization than in normal tissues. Wound healing_sentence_159

Until the entire wound area is resurfaced, the only epithelial cells to proliferate are at the wound edges. Wound healing_sentence_160

Growth factors, stimulated by integrins and MMPs, cause cells to proliferate at the wound edges. Wound healing_sentence_161

Keratinocytes themselves also produce and secrete factors, including growth factors and basement membrane proteins, which aid both in epithelialization and in other phases of healing. Wound healing_sentence_162

Growth factors are also important for the innate immune defense of skin wounds by stimulation of the production of antimicrobial peptides and neutrophil chemotactic cytokines in keratinocytes. Wound healing_sentence_163

Keratinocytes continue migrating across the wound bed until cells from either side meet in the middle, at which point contact inhibition causes them to stop migrating. Wound healing_sentence_164

When they have finished migrating, the keratinocytes secrete the proteins that form the new basement membrane. Wound healing_sentence_165

Cells reverse the morphological changes they underwent in order to begin migrating; they reestablish desmosomes and hemidesmosomes and become anchored once again to the basement membrane. Wound healing_sentence_166

Basal cells begin to divide and differentiate in the same manner as they do in normal skin to reestablish the strata found in reepithelialized skin. Wound healing_sentence_167

Contraction Wound healing_section_14

Contraction is a key phase of wound healing with repair. Wound healing_sentence_168

If contraction continues for too long, it can lead to disfigurement and loss of function. Wound healing_sentence_169

Thus there is a great interest in understanding the biology of wound contraction, which can be modelled in vitro using the collagen gel contraction assay or the dermal equivalent model. Wound healing_sentence_170

Contraction commences approximately a week after wounding, when fibroblasts have differentiated into myofibroblasts. Wound healing_sentence_171

In full thickness wounds, contraction peaks at 5 to 15 days post wounding. Wound healing_sentence_172

Contraction can last for several weeks and continues even after the wound is completely reepithelialized. Wound healing_sentence_173

A large wound can become 40 to 80% smaller after contraction. Wound healing_sentence_174

Wounds can contract at a speed of up to 0.75 mm per day, depending on how loose the tissue in the wounded area is. Wound healing_sentence_175

Contraction usually does not occur symmetrically; rather most wounds have an 'axis of contraction' which allows for greater organization and alignment of cells with collagen. Wound healing_sentence_176

At first, contraction occurs without myofibroblast involvement. Wound healing_sentence_177

Later, fibroblasts, stimulated by growth factors, differentiate into myofibroblasts. Wound healing_sentence_178

Myofibroblasts, which are similar to smooth muscle cells, are responsible for contraction. Wound healing_sentence_179

Myofibroblasts contain the same kind of actin as that found in smooth muscle cells. Wound healing_sentence_180

Myofibroblasts are attracted by fibronectin and growth factors and they move along fibronectin linked to fibrin in the provisional ECM in order to reach the wound edges. Wound healing_sentence_181

They form connections to the ECM at the wound edges, and they attach to each other and to the wound edges by desmosomes. Wound healing_sentence_182

Also, at an adhesion called the fibronexus, actin in the myofibroblast is linked across the cell membrane to molecules in the extracellular matrix like fibronectin and collagen. Wound healing_sentence_183

Myofibroblasts have many such adhesions, which allow them to pull the ECM when they contract, reducing the wound size. Wound healing_sentence_184

In this part of contraction, closure occurs more quickly than in the first, myofibroblast-independent part. Wound healing_sentence_185

As the actin in myofibroblasts contracts, the wound edges are pulled together. Wound healing_sentence_186

Fibroblasts lay down collagen to reinforce the wound as myofibroblasts contract. Wound healing_sentence_187

The contraction stage in proliferation ends as myofibroblasts stop contracting and commit apoptosis. Wound healing_sentence_188

The breakdown of the provisional matrix leads to a decrease in hyaluronic acid and an increase in chondroitin sulfate, which gradually triggers fibroblasts to stop migrating and proliferating. Wound healing_sentence_189

These events signal the onset of the maturation stage of wound healing. Wound healing_sentence_190

Maturation and remodeling Wound healing_section_15

When the levels of collagen production and degradation equalize, the maturation phase of tissue repair is said to have begun. Wound healing_sentence_191

During maturation, type III collagen, which is prevalent during proliferation, is replaced by type I collagen. Wound healing_sentence_192

Originally disorganized collagen fibers are rearranged, cross-linked, and aligned along tension lines. Wound healing_sentence_193

The onset of the maturation phase may vary extensively, depending on the size of the wound and whether it was initially closed or left open, ranging from approximately 3 days to 3 weeks. Wound healing_sentence_194

The maturation phase can last for a year or longer, similarly depending on wound type. Wound healing_sentence_195

As the phase progresses, the tensile strength of the wound increases. Wound healing_sentence_196

Collagen will reach approximately 20% of its tensile strength after 3 weeks, increasing to 80% by 12th week. Wound healing_sentence_197

The maximum scar strength is 80% of that of unwounded skin. Wound healing_sentence_198

Since activity at the wound site is reduced, the scar loses its red appearance as blood vessels that are no longer needed are removed by apoptosis. Wound healing_sentence_199

The phases of wound healing normally progress in a predictable, timely manner; if they do not, healing may progress inappropriately to either a chronic wound such as a venous ulcer or pathological scarring such as a keloid scar. Wound healing_sentence_200

Factors affecting wound healing Wound healing_section_16

Many factors controlling the efficacy, speed, and manner of wound healing fall under two types: local and systemic factors. Wound healing_sentence_201

Local factors Wound healing_section_17

Wound healing_unordered_list_3

  • Moisture; keeping a wound moist rather than dry makes wound healing more rapid and with less pain and less scarringWound healing_item_3_14
  • Mechanical factorsWound healing_item_3_15
  • OedemaWound healing_item_3_16
  • Ionizing radiationWound healing_item_3_17
  • Faulty technique of wound closureWound healing_item_3_18
  • Ischemia and necrosisWound healing_item_3_19
  • Foreign bodies. Sharp, small foreign bodies can penetrate the skin leaving little surface wound but causing internal injury and internal bleeding. For a glass foreign body, "frequently, an innocent skin wound disguises the extensive nature of the injuries beneath". First-degree nerve injury requires a few hours to a few weeks to recover. If a foreign body passes by a nerve and causes first-degree nerve injury during entry, then the sensation of the foreign body or pain due to internal wounding may be delayed by a few hours to a few weeks after entry. A sudden increase in pain during the first few weeks of wound healing could be a sign of a recovered nerve reporting internal injuries rather than a newly developed infection.Wound healing_item_3_20
  • Low oxygen tensionWound healing_item_3_21
  • PerfusionWound healing_item_3_22

Systemic factors Wound healing_section_18

Wound healing_unordered_list_4

  • InflammationWound healing_item_4_23
  • Diabetes – Individuals with diabetes demonstrate reduced capability in the healing of acute wounds. Additionally, diabetic individuals are susceptible to developing chronic diabetic foot ulcers, a serious complication of diabetes which affects 15% of people with diabetes and accounts for 84% of all diabetes-related lower leg amputations. The impaired healing abilities of diabetics with diabetic foot ulcers and/or acute wounds involves multiple pathophysiological mechanisms. This impaired healing involves hypoxia, fibroblast and epidermal cell dysfunction, impaired angiogenesis and neovascularization, high levels of metalloproteases, damage from reactive oxygen species and AGEs (advanced glycation end-products), decreased host immune resistance, and neuropathy.Wound healing_item_4_24
  • Nutrients – Malnutrition or nutritional deficiencies have a recognizable impact on wound healing post trauma or surgical intervention. Nutrients including proteins, carbohydrates, arginine, glutamine, polyunsaturated fatty acids, vitamin A, vitamin C, vitamin E, magnesium, copper, zinc and iron all play significant roles in wound healing. Fats and carbohydrates provide the majority of energy required for wound healing. Glucose is the most prominent source of fuel and it is used to create cellular ATP, providing energy for angiogenesis and the deposition of new tissues. As the nutritional needs of each patient and their associated wound are complex, it is suggested that tailored nutritional support would benefit both acute and chronic wound healing.Wound healing_item_4_25
  • Metabolic diseasesWound healing_item_4_26
  • ImmunosuppressionWound healing_item_4_27
  • Connective tissue disordersWound healing_item_4_28
  • Smoking – Smoking causes a delay in the speed of wound repair notably in the proliferative and inflammatory phases. It also increases the likelihood of certain complications such as wound rupture, wound and flap necrosis, decrease in wound tensile strength and infection. Passive smoking also impairs a proper wound healing process.Wound healing_item_4_29
  • Age – Increased age (over 60 years) is a risk factor for impaired wound healing. It is recognized that, in older adults of otherwise overall good health, the effects of aging causes a temporal delay in healing, but no major impairment with regard to the quality of healing. Delayed wound healing in patients of increasing age is associated with altered inflammatory response; for example delayed T-cell infiltration of the wound with alterations in the production of chemokines, and reduced macrophage phagocytic capacity.Wound healing_item_4_30
  • Alcohol – Alcohol consumption impairs wound healing and also increases the chances of infection. Alcohol affects the proliferative phase of healing. A single unit of alcohol causes a negative effect on re-epithelialization, wound closure, collagen production and angiogenesis.Wound healing_item_4_31

In the 2000s, there were proposed the first Mathematical models of the healing process, based on simplified assumptions and on a system of differential equations solved through MATLAB. Wound healing_sentence_202

The data shed an experimental evidence for which the "rate of the healing process" appears to be "highly influenced by the activity and size of the injury itself as well as the activity of the healing agent." Wound healing_sentence_203

Research and development Wound healing_section_19

Up until about 2000, the classic paradigm of wound healing, involving stem cells restricted to organ-specific lineages, had never been seriously challenged. Wound healing_sentence_204

Since then, the notion of adult stem cells having cellular plasticity or the ability to differentiate into non-lineage cells has emerged as an alternative explanation. Wound healing_sentence_205

To be more specific, hematopoietic progenitor cells (that give rise to mature cells in the blood) may have the ability de-differentiate back into hematopoietic stem cells and/or transdifferentiate into non-lineage cells, such as fibroblasts. Wound healing_sentence_206

Stem cells and cellular plasticity Wound healing_section_20

Multipotent adult stem cells have the capacity to be self-renewing and give rise to different cell types. Wound healing_sentence_207

Stem cells give rise to progenitor cells, which are cells that are not self-renewing, but can generate several types of cells. Wound healing_sentence_208

The extent of stem cell involvement in cutaneous (skin) wound healing is complex and not fully understood. Wound healing_sentence_209

It is thought that the epidermis and dermis are reconstituted by mitotically active stem cells that reside at the apex of rete ridges (basal stem cells or BSC), the bulge of hair follicles (hair follicular stem cell or HFSC), and the papillary dermis (dermal stem cells). Wound healing_sentence_210

Moreover, bone marrow may also contain stem cells that play a major role in cutaneous wound healing. Wound healing_sentence_211

In rare circumstances, such as extensive cutaneous injury, self-renewal subpopulations in the bone marrow are induced to participate in the healing process, whereby they give rise to collagen-secreting cells that seem to play a role during wound repair. Wound healing_sentence_212

These two self-renewal subpopulations are (1) bone marrow-derived mesenchymal stem cells (MSC) and (2) hematopoietic stem cells (HSC). Wound healing_sentence_213

Bone marrow also harbors a progenitor subpopulation (endothelial progenitor cells or EPC) that, in the same type of setting, are mobilized to aid in the reconstruction of blood vessels. Wound healing_sentence_214

Moreover, it thought that, extensive injury to skin also promotes the early trafficking of a unique subclass of leukocytes (circulating fibrocytes) to the injured region, where they perform various functions related to wound healing. Wound healing_sentence_215

Wound repair versus regeneration Wound healing_section_21

An injury is an interruption of morphology and/or functionality of a given tissue. Wound healing_sentence_216

After injury, structural tissue heals with incomplete or complete regeneration. Wound healing_sentence_217

Tissue without an interruption to the morphology almost always completely regenerates. Wound healing_sentence_218

An example of complete regeneration without an interruption of the morphology is non-injured tissue, such as skin. Wound healing_sentence_219

Non-injured skin has a continued replacement and regeneration of cells which always results in complete regeneration. Wound healing_sentence_220

There is a subtle distinction between 'repair' and 'regeneration'. Wound healing_sentence_221

Repair means incomplete regeneration. Wound healing_sentence_222

Repair or incomplete regeneration, refers to the physiologic adaptation of an organ after injury in an effort to re-establish continuity without regards to exact replacement of lost/damaged tissue. Wound healing_sentence_223

True tissue regeneration or complete regeneration, refers to the replacement of lost/damaged tissue with an ‘exact’ copy, such that both morphology and functionality are completely restored. Wound healing_sentence_224

Though after injury mammals can completely regenerate spontaneously, they usually do not completely regenerate. Wound healing_sentence_225

An example of a tissue regenerating completely after an interruption of morphology is the endometrium; the endometrium after the process of breakdown via the menstruation cycle heals with complete regeneration. Wound healing_sentence_226

In some instances, after a tissue breakdown, such as in skin, a regeneration closer to complete regeneration may be induced by the use of biodegradable (collagen-glycoaminoglycan) scaffolds. Wound healing_sentence_227

These scaffolds are structurally analogous to extracellular matrix (ECM) found in normal/un-injured dermis. Wound healing_sentence_228

Fundamental conditions required for tissue regeneration often oppose conditions that favor efficient wound repair, including inhibition of (1) platelet activation, (2) inflammatory response, and (3) wound contraction. Wound healing_sentence_229

In addition to providing support for fibroblast and endothelial cell attachment, biodegradable scaffolds inhibit wound contraction, thereby allowing the healing process to proceed towards a more-regenerative/less-scarring pathway. Wound healing_sentence_230

Pharmaceutical agents have been investigated which may be able to turn off myofibroblast differentiation. Wound healing_sentence_231

A new way of thinking derived from the notion that heparan sulfates are key player in tissue homeostasis: the process that makes the tissue replace dead cells by identical cells. Wound healing_sentence_232

In wound areas, tissue homeostasis is lost as the heparan sulfates are degraded preventing the replacement of dead cells by identical cells. Wound healing_sentence_233

Heparan sulfate analogues cannot be degraded by all know heparanases and glycanases and bind to the free heparin sulfate binding spots on the ECM, therefore preserving the normal tissue homeostasis and preventing scarring. Wound healing_sentence_234

Repair or regeneration with regards to hypoxia-inducible factor 1-alpha (HIF-1a). Wound healing_sentence_235

In normal circumstances after injury HIF-1a is degraded by prolyl hydroxylases (PHDs). Wound healing_sentence_236

Scientists found that the simple up-regulation of HIF-1a via PHD inhibitors regenerates lost or damaged tissue in mammals that have a repair response; and the continued down-regulation of Hif-1a results in healing with a scarring response in mammals with a previous regenerative response to the loss of tissue. Wound healing_sentence_237

The act of regulating HIF-1a can either turn off, or turn on the key process of mammalian regeneration. Wound healing_sentence_238

Further information: Liver regeneration Wound healing_sentence_239

Scarless wound healing Wound healing_section_22

Scarless wound healing is a concept based on the healing or repair of the skin (or other tissue/organs) after injury with the aim of healing with subjectively and relatively less scar tissue than normally expected. Wound healing_sentence_240

Scarless healing is sometimes mixed up with the concept of scar free healing, which is wound healing which results in absolutely no scar (free of scarring). Wound healing_sentence_241

However they are different concepts. Wound healing_sentence_242

A reverse to scarless wound healing is scarification (wound healing to scar more). Wound healing_sentence_243

Historically, certain cultures consider scarification attractive; however, this is generally not the case in the modern western society, in which many patients are turning to plastic surgery clinics with unrealistic expectations. Wound healing_sentence_244

Depending on scar type, treatment may be invasive (intralesional steroid injections, surgery) and/or conservative (compression therapy, topical silicone gel, brachytherapy, photodynamic therapy). Wound healing_sentence_245

Clinical judgment is necessary to successfully balance the potential benefits of the various treatments available against the likelihood of a poor response and possible complications resulting from these treatments. Wound healing_sentence_246

Many of these treatments may only have a placebo effect, and the evidence base for the use of many current treatments is poor. Wound healing_sentence_247

Since the 1960s, comprehension of the basic biologic processes involved in wound repair and tissue regeneration have expanded due to advances in cellular and molecular biology. Wound healing_sentence_248

Currently, the principal goals in wound management are to achieve rapid wound closure with a functional tissue that has minimal aesthetic scarring. Wound healing_sentence_249

However, the ultimate goal of wound healing biology is to induce a more perfect reconstruction of the wound area. Wound healing_sentence_250

Scarless wound healing only occurs in mammalian foetal tissues and complete regeneration is limited to lower vertebrates, such as salamanders, and invertebrates. Wound healing_sentence_251

In adult humans, injured tissue are repaired by collagen deposition, collagen remodelling and eventual scar formation, where fetal wound healing is believed to be more of a regenerative process with minimal or no scar formation. Wound healing_sentence_252

Therefore, foetal wound healing can be used to provide an accessible mammalian model of an optimal healing response in adult human tissues. Wound healing_sentence_253

Clues as to how this might be achieved come from studies of wound healing in embryos, where repair is fast and efficient and results in essentially perfect regeneration of any lost tissue. Wound healing_sentence_254

The etymology of the term scarless wound healing has a long history. Wound healing_sentence_255

In print the antiquated concept of scarless healing was brought up the early 20th century and appeared in a paper published in the London Lancet. Wound healing_sentence_256

This process involved cutting in a surgical slant, instead of a right angle…; it was described in various Newspapers. Wound healing_sentence_257

Cancer Wound healing_section_23

After inflammation, restoration of normal tissue integrity and function is preserved by feedback interactions between diverse cell types mediated by adhesion molecules and secreted cytokines. Wound healing_sentence_258

Disruption of normal feedback mechanisms in cancer threatens tissue integrity and enables a malignant tumor to escape the immune system. Wound healing_sentence_259

An example of the importance of the wound healing response within tumors is illustrated in work by Howard Chang and colleagues at Stanford University studying Breast cancers. Wound healing_sentence_260

Oral Collagen Supplements Wound healing_section_24

Preliminary results are promising for the and skin aging.Oral collagen supplements also increase skin elasticity, hydration, and dermal collagen density. Wound healing_sentence_261

Collagen supplementation is generally safe with no reported adverse events. Wound healing_sentence_262

Further studies are needed to elucidate medical use in skin barrier diseases such as atopic dermatitis and to determine optimal dosing regimens. Wound healing_sentence_263

Simulating wound healing from a growth perspective Wound healing_section_25

Considerable effort has been devoted to understanding the physical relationships governing wound healing and subsequent scarring, with mathematical models and simulations developed to elucidate these relationships. Wound healing_sentence_264

The growth of tissue around the wound site is a result of the migration of cells and collagen deposition by these cells. Wound healing_sentence_265

The alignment of collagen describes the degree of scarring; basket-weave orientation of collagen is characteristic of normal skin, whereas aligned collagen fibers lead to significant scarring. Wound healing_sentence_266

It has been shown that the growth of tissue and extent of scar formation can be controlled by modulating the stress at a wound site. Wound healing_sentence_267

The growth of tissue can be simulated using the aforementioned relationships from a biochemical and biomechanical point of view. Wound healing_sentence_268

The biologically active chemicals that play an important role in wound healing are modeled with Fickian diffusion to generate concentration profiles. Wound healing_sentence_269

The balance equation for open systems when modeling wound healing incorporates mass growth due to cell migration and proliferation. Wound healing_sentence_270

Here the following equation is used: Wound healing_sentence_271

Dtρ0 = Div (R) + R0, Wound healing_sentence_272

where ρ represents mass density, R represents a mass flux (from cell migration), and R0 represents a mass source (from cell proliferation, division, or enlargement). Wound healing_sentence_273

Relationships like these can be incorporated into an agent-based models, where the sensitivity to single parameters such as initial collagen alignment, cytokine properties, and cell proliferation rates can be tested. Wound healing_sentence_274

Wound closure intentions Wound healing_section_26

Successful wound healing is dependent on various cell types, molecular mediators and structural elements. Wound healing_sentence_275

Primary intention Wound healing_section_27

Primary intention is the healing of a clean wound without tissue loss. Wound healing_sentence_276

In this process, wound edges are brought together, so that they are adjacent to each other (re-approximated). Wound healing_sentence_277

Wound closure is performed with sutures (stitches), staples, or adhesive tape or glue. Wound healing_sentence_278

Primary intention can only be implemented when the wound is precise and there is minimal disruption to the local tissue and the epithelial basement membrane, e.g. surgical incisions. Wound healing_sentence_279

This process is faster than healing by secondary intention. Wound healing_sentence_280

There is also less scarring associated with primary intention, as there are no large tissue losses to be filled with granulation tissue. Wound healing_sentence_281

(Primary intention does require some granulation tissue to form.) Wound healing_sentence_282

Wound healing_unordered_list_5

  • Examples of primary intention include: well-repaired lacerations, well reduced bone fractures, healing after flap surgery.Wound healing_item_5_32
  • Early removal of dressings from clean or clean-contaminated wounds does affect primary healing of wounds.Wound healing_item_5_33

Secondary intention Wound healing_section_28

Wound healing_unordered_list_6

  • Secondary intention is implemented when primary intention is not possible.Wound healing_item_6_34
  • This is due to wounds being created by major trauma in which there has been a significant loss in tissue or tissue damage.Wound healing_item_6_35
  • The wound is allowed to granulate.Wound healing_item_6_36
  • Surgeon may pack the wound with a gauze or use a drainage system.Wound healing_item_6_37
  • Granulation results in a broader scar.Wound healing_item_6_38
  • Healing process can be slow due to presence of drainage from infection.Wound healing_item_6_39
  • Wound care must be performed daily to encourage wound debris removal to allow for granulation tissue formation.Wound healing_item_6_40
  • Using antibiotics or antiseptics for the surgical wound healing by secondary intention is controversial.Wound healing_item_6_41
  • Examples: gingivectomy, gingivoplasty, tooth extraction sockets, poorly reduced fractures, burns, severe lacerations, pressure ulcers.Wound healing_item_6_42
  • There is insufficient evidence that the choice of dressings or topical agents affects the secondary healing of wounds.Wound healing_item_6_43
  • There is lack of evidence for the effectiveness of negative pressure wound therapy in wound healing by secondary intention.Wound healing_item_6_44

Tertiary intention Wound healing_section_29

(Delayed primary closure or secondary suture): Wound healing_sentence_283

Wound healing_unordered_list_7

  • The wound is initially cleaned, debrided and observed, typically 4 or 5 days before closure.Wound healing_item_7_45
  • The wound is purposely left open.Wound healing_item_7_46
  • Examples: healing of wounds by use of tissue grafts.Wound healing_item_7_47

If the wound edges are not reapproximated immediately, delayed primary wound healing transpires. Wound healing_sentence_284

This type of healing may be desired in the case of contaminated wounds. Wound healing_sentence_285

By the fourth day, phagocytosis of contaminated tissues is well underway, and the processes of epithelization, collagen deposition, and maturation are occurring. Wound healing_sentence_286

Foreign materials are walled off by macrophages that may metamorphose into epithelioid cells, which are encircled by mononuclear leukocytes, forming granulomas. Wound healing_sentence_287

Usually the wound is closed surgically at this juncture, and if the "cleansing" of the wound is incomplete, chronic inflammation can ensue, resulting in prominent scarring. Wound healing_sentence_288

Overview of involved growth factors Wound healing_section_30

Following are the main growth factors involved in wound healing: Wound healing_sentence_289

Wound healing_table_general_0

Growth factorWound healing_header_cell_0_0_0 AbbreviationWound healing_header_cell_0_0_1 Main originsWound healing_header_cell_0_0_2 EffectsWound healing_header_cell_0_0_3
Epidermal growth factorWound healing_header_cell_0_1_0 EGFWound healing_cell_0_1_1 Wound healing_cell_0_1_2 Wound healing_cell_0_1_3
Transforming growth factor-αWound healing_header_cell_0_2_0 TGF-αWound healing_cell_0_2_1 Wound healing_cell_0_2_2 Wound healing_cell_0_2_3
Hepatocyte growth factorWound healing_header_cell_0_3_0 HGFWound healing_cell_0_3_1 Wound healing_cell_0_3_2 Wound healing_cell_0_3_3
Vascular endothelial growth factorWound healing_header_cell_0_4_0 VEGFWound healing_cell_0_4_1 Wound healing_cell_0_4_2 Wound healing_cell_0_4_3
Platelet derived growth factorWound healing_header_cell_0_5_0 PDGFWound healing_cell_0_5_1 Wound healing_cell_0_5_2 Wound healing_cell_0_5_3
Fibroblast growth factor 1 and 2Wound healing_header_cell_0_6_0 FGF-1, −2Wound healing_cell_0_6_1 Wound healing_cell_0_6_2 Wound healing_cell_0_6_3
Transforming growth factor-βWound healing_header_cell_0_7_0 TGF-βWound healing_cell_0_7_1 Wound healing_cell_0_7_2 Wound healing_cell_0_7_3
Keratinocyte growth factorWound healing_header_cell_0_8_0 KGFWound healing_cell_0_8_1 Wound healing_cell_0_8_2 Wound healing_cell_0_8_3
Unless else specified in boxes, then reference is:Wound healing_cell_0_9_0

Complications of wound healing Wound healing_section_31

The major complications are many: Wound healing_sentence_290

Wound healing_ordered_list_8

  1. Deficient scar formation: Results in wound dehiscence or rupture of the wound due to inadequate formation of granulation tissue.Wound healing_item_8_48
  2. Excessive scar formation: Hypertrophic scar, keloid, desmoid.Wound healing_item_8_49
  3. Exuberant granulation (proud flesh).Wound healing_item_8_50
  4. Deficient contraction (in skin grafts) or excessive contraction (in burns).Wound healing_item_8_51
  5. Others: Dystrophic calcification, pigmentary changes, painful scars, incisional herniaWound healing_item_8_52

Other complications can include Infection and Marjolin's ulcer. Wound healing_sentence_291

Biologics, skin substitutes, biomembranes and scaffolds Wound healing_section_32

Advancements in the clinical understanding of wounds and their pathophysiology have commanded significant biomedical innovations in the treatment of acute, chronic, and other types of wounds. Wound healing_sentence_292

Many biologics, skin substitutes, biomembranes and scaffolds have been developed to facilitate wound healing through various mechanisms. Wound healing_sentence_293

This includes a number of products under the trade names such as Epicel, Laserskin, Transcyte, Dermagraft, AlloDerm/Strattice, Biobrane, Integra, Apligraf, OrCel, GraftJacket and PermaDerm. Wound healing_sentence_294

See also Wound healing_section_33

Credits to the contents of this page go to the authors of the corresponding Wikipedia page: en.wikipedia.org/wiki/Wound healing.