Wound healing is a complex process in which skin improves itself after an injury. In this article, wound healing is described in a time line separate from the physical attributes (phase) which is a post-traumatic repair process. In undamaged skin, the epidermis (the surface layer) and the dermis (the deeper layer) form a protective barrier against the external environment. When the barrier is damaged, the sequence of biochemical events is set into motion to repair the damage. This process is divided into predictable phases: blood clotting (hemostasis), inflammation, tissue growth (proliferation), and tissue remodeling (maturation). Blood clots can be considered as part of the inflammatory stage rather than at a separate stage.
- Hemostasis (blood clots): In the first few minutes of injury, the platelets in the blood begin to stick to the injured site. It activates platelets, causing some things to happen. They change to an amorphous form, more suitable for freezing, and they release chemical signals to increase clotting. This results in fibrin activation, which forms the mesh and acts as a "glue" to bind the platelets to each other. This creates a clot that serves to break the gap in the blood vessels, slowing/preventing further bleeding.
- Inflammation: During this phase, damaged and dead cells are cleaned, along with bacteria and pathogens or other debris. It occurs through the process of phagocytosis, in which white blood cells "eat" debris by swallowing it. The growth factor derived from platelets is released into wounds that cause migration and cell division during the proliferative phase.
- 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 temporary extracellular matrix (ECM) by excreting collagen and fibronectin. Simultaneously, re-epithelialization of the epidermis occurs, in which epithelial cells multiply and 'crawl' over the wound bed, providing a cover for the new tissue. In wound contraction, myofibroblasts reduce the size of the wound by gripping the wound edges and contracting using mechanisms that resemble smooth muscle cells. When the cell's role is almost complete, unneeded cells experience apoptosis.
- Remodeling: During maturation and remodeling, collagen is rearranged along the line of stress, and cells that are no longer needed are eliminated by programmed cell death, or apoptosis.
The wound healing process is not only complex but also fragile, and prone to disorders or failures that lead to the formation of chronic wounds that do not heal. Factors contributing to chronic wounds that do not cure are diabetes, venous diseases or arteries, infections, and advanced age metabolic deficiencies.
Wound care encourages and accelerates wound healing through cleansing and protection from reinjury or infection. Depending on the needs of each patient, it can range from the simplest first aid to all nursing specialties such as wound care, ostomy, and nursing care and burn centers.
Video Wound healing
Timing and reepithelialization
Timing is important for wound healing. Critically, reepithelialization time of the wound can decide the healing result. If tissue epithelization over a bare area is slow, scars will form for weeks, or months; If epithelialization of the wound area is rapid, healing will result in regeneration.
Maps Wound healing
Initial vs. mobile phase
Wound healing is classically divided into hemostasis, inflammation, proliferation, and remodeling. Despite useful constructs, this model employs considerable overlap between individual phases. A recent complementary model has been described in which many elements of wound healing are more clearly described. The importance of this new model becomes more apparent through its usefulness in the field of regenerative medicine and tissue engineering (see Research and development section below). In this construct, the wound healing process is divided into two main phases: initial phase and mobile phase :
The initial phase, which begins shortly after a skin injury, involves the cellular and molecular cascade leading to hemostasis and the formation of an early and urgent maternal and extracellular matrix that provides structural staging for cellular attachment and subsequent cellular proliferation.
The cellular phase involves several types of cells working together to install an inflammatory response, synthesize the granulation tissue, and restore the epithelial layer. Cellular cellular subdivisions are: [1] Macrophages and inflammatory components (within 1-2 days), [2] Epithelial-mesenphal interactions: re-epithelization (phenotypic changes within hours, migration begins on day 1 or 2), [3 Fibroblas and myofibroblasts: progressive smoothing, collagen production, and matrix contraction (between day 4 and day 14), [4] endothelial cells and angiogenesis (beginning on day 4), [5] dermal matrix: fabrication elements (starting on day 4, lasts 2 weeks) and changes/remodeling (starts after week 2, last week to month - depending on wound size).
Inflammatory phase
Just before the inflammatory phase begins, a coagulation cascade occurs to reach hemostasis, or stop blood loss through a fibrin clot. Subsequently, 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 wound healing proliferation phase.
Clotting cascade
When the first tissue is injured, the blood in contact with collagen, triggers the blood platelets to begin secreting the inflammatory factor. Platelets also express sticky glycoproteins on their cell membranes that allow them to aggregate, forming mass.
Fibrin and fibronectin cross-link together and form a plug that traps proteins and particles and prevents further blood loss. These fibrin-fibronectin plugs are also the main structural support for wounds until collagen is stored. Cells migrate using this plug as a matrix to be crawled, and platelets attach to it and secrete a factor. The clot is finally released and replaced with granulation tissue and then with collagen.
Platelets, the cells that are present in the highest amount immediately after the wound occurs, release the mediator into the blood, including cytokines and growth factors. Growth factors stimulate cells to accelerate their division rate. Platelets release other proinflammatory factors such as serotonin, bradykinin, prostaglandins, prostacyclins, thromboxane, and histamine, which serve several purposes, including increasing cell proliferation and migration to the area and causing the blood vessels to become dilated and porous. In many cases, traumatized thrombocyte performs the same function as tissue macrophages and mast cells exposed to microbial molecular signs of infection: they become active, and secrete the molecular mediators - vasoactive amines, eicosanoids, and cytokines - which initiate the inflammatory process.
Vasoconstriction and vasodilation
As soon as the blood vessels are broken, the ruptured cell membrane releases inflammatory factors such as thromboxanes and prostaglandins that cause the vessels to become seizures to prevent blood loss and to collect cells and inflammatory factors in the area. This vasoconstriction lasts for five to ten minutes and is followed by vasodilation, dilation of the blood vessels, which peaks about 20 minutes after the wound. Vasodilation is the end result of the factors released by platelets and other cells. The main factor involved in causing vasodilation is histamine. Histamine also causes blood vessels to become porous, allowing the tissues to become edematous because of proteins from leaking blood flow to the extravascular space, which increases the osmolar load and draws water into the area. Increased porosity of blood vessels also facilitates the entry of inflammatory cells such as leukocytes to the wound site from the bloodstream.
Polymorphonuclear neutrophils
Within one hour of injury, polymorphonuclear neutrophils (PMN) arrive at the site of the wound and become the dominant cells in the wound for the first two days after the injury occurs, with a very high number on the second day. They are attracted to the site by fibronectin, growth factors, and substances such as quinine. Neutrophils phagocytise debris and kill bacteria by releasing free radicals in so-called 'breathing bursts. They also clean the wound by removing proteases that destroy damaged tissue. The functional neutrophils at the wound site only have a life span of about 2 days, so they usually experience apoptosis after completing their task and are swallowed and degraded by macrophages.
Other leukocytes to enter the area include helper T cells, which secrete cytokines to cause more T cells to divide and increase inflammation and increase vasodilation and permeability of blood vessels. T cells also increase macrophage activity.
Macrophages
One role of macrophages is to phagocytate phagocytes, bacteria, and other damaged tissues, and they also damage damaged tissue by releasing proteases.
Macrophages function in regeneration and are essential for wound healing. They are stimulated by the low oxygen content in the vicinity to produce factors that induce and accelerate angiogenesis and they also stimulate cells that reshape wounds, make granulation tissue, and place new extracellular matrices. By secreting these factors, macrophages contribute to driving the wound healing process to the next phase. They replaced PMNs as the dominant cells in the wound by two days after the injury.
The spleen contains half the body's monocytes in reserves that are ready to be spread to the injured tissue. Attracted to the wound site by growth factors released by platelets and other cells, monocytes from the bloodstream enter the area through the walls of blood vessels. The number of monocytes at the top of the wound is one to one and a half days after the injury occurs. Once they are at the wound site, the monocyte matures into macrophages. Macrophages also secrete factors such as growth factors and other cytokines, especially during the third and fourth post-injury days. These factors attract the cells involved in the healing proliferation stage to the area.
In wound healing that results in incomplete repair, scar contractions occur, bringing various gradations of structural imperfections, deformities and problems with flexibility. Macrophages can withstand the contraction phase. Scientists have reported that removing macrophages from salamanders results in the failure of a typical regenerative response (limb regeneration), in turn leading to an improvement (scarring) response.
Decrease in the inflammatory phase
When inflammation dies, fewer inflammatory factors are secreted, existing ones are damaged, and the number of neutrophils and macrophages is reduced at the wound site. These changes indicate that the inflammatory phase has ended and the proliferation phase is underway. In vitro evidence, obtained by using a dermal equivalent model, shows that the presence of macrophages actually delayed wound contractions and thus loss of macrophages from wounds may be important for the next phase to occur.
Because inflammation plays a role in fighting infections, clearing debris and encouraging the proliferation phase, it is an important part of healing. However, inflammation can cause tissue damage if it lasts too long. Thus reduction of inflammation is often a goal in therapeutic settings. The inflammation lasts as long as there is debris in the wound. Thus, if the individual immune system is disrupted and unable to clear debris from wounds and/or if excessive detritus, smoothed tissue, or microbial biofilm is present in the wound, these factors can cause prolonged inflammatory phases and prevent injury. from properly initiating the healing proliferation phase. This can cause chronic wounds.
Proliferative phase
About two or three days after the wound occurs, fibroblasts begin to enter the wound site, marking the beginning of the proliferative phase even before the inflammatory phase ends. As with other wound healing phases, the steps in the proliferation phase do not occur in a series but rather partially overlap in time.
Angiogenesis
Also called neovascularization, angiogenesis processes occur in conjunction with fibroblast proliferation when endothelial cells migrate to the wound area. Because the activity of fibroblasts and epithelial cells requires oxygen and nutrients, angiogenesis is essential for other stages of wound healing, such as epidermal migration and fibroblasts. The tissues in which angiogenesis has occurred usually appear red (erythematous) due to the presence of capillaries.
Angiogenesis occurs in an overlapping phase in response to inflammation:
The stem cells of the endothelial cells, which originate from unharmed blood vessel sections, develop pseudopodia and push through the ECM to place the wound to form new blood vessels.
Endothelial cells are attracted to the wound area by fibronectin found in fibrin scabs and chemotactically by angiogenic factors released by other cells, eg from macrophages and platelets when in low oxygen environments. Endothelial growth and proliferation are also directly stimulated by hypoxia, and the presence of lactic acid in the wound. For example, hypoxia stimulates endothelial transcription factor, hypoxia-inducible factor (HIF) to transfactivate a set of proliferative genes including vascular endothelial growth factor (VEGF) and glucose transporter 1 (GLUT1).
To migrate, endothelial cells require collagenase and plasminogen activator to decrease clot and part of ECM. Zinc-dependent metalloproteinase digests basement membrane and ECM to allow cell migration, proliferation and angiogenesis.
When macrophages and other growth-producing cells are no longer in an acidic, lactic acid environment, they stop producing angiogenic factors. Thus, when the tissue is sufficiently diffused, the migration and proliferation of endothelial cells decreases. Eventually blood vessels that are no longer needed die by apoptosis.
Fibroplasia and granulation tissue formation
Along with angiogenesis, fibroblasts begin to accumulate at the site of the wound. Fibroblasts begin entering the wound site two to five days after injury when the inflammatory phase ends, and their number peaks at one to two weeks after the wound. At the end of the first week, fibroblasts are the major cells in the wound. Fibroplasia lasts two to four weeks after injury.
As a model of the mechanism of fibroplasia can be conceptualized as an analogous process to angiogenesis (see above) - only the types of cells involved are fibroblasts rather than endothelial cells. Initially there is a latent phase in which the wound undergoes plasma exudation, inflammatory decontamination and debridement. Edema improves histological access to wounds for fibroplastic migration later. Second, as inflammation approaches completion, macrophages and mast cells release the growth of fibroblasts and chemotactic factors to activate fibroblasts from nearby tissues. Fibroblasts at this stage break away from surrounding cells and ECM. Phagocytes subsequently release proteases that break down ECM from neighboring tissues, freeing the activated fibroblasts to proliferate and migrate toward the wound. The difference between vascular sprouting and fibroblast proliferation is that the first is enhanced by hypoxia, while the latter is inhibited by hypoxia. The fibroblastic connective tissue that is deposited becomes matured by removing the ECM into the extracellular space, forming a granulation tissue (see below). The last collagen is saved to ECM.
In the first two or three days after injury, fibroblasts primarily migrate and proliferate, while later, they are the primary cells that place the collagen matrix at the wound site. The origin of these fibroblasts is thought to originate from adjacent unharmed skin tissue (though new evidence suggests that some originate from adult blood circulating adult/adult precursors). Initially fibroblasts utilize fibrin cross-linking fibers (well formed at the end of the inflammatory phase) to migrate across the wound, then follow fibronectin. Fibroblasts then store the substance of the soil into the wound bed, and then collagen, which they can obey for migration.
The granulation tissue serves as an imperfect tissue, and begins to appear in wounds that have been during the inflammatory phase, two to five days post-wound, and continue to grow until the bed sores are closed. The granulation tissue consists of new blood vessels, fibroblasts, inflammatory cells, endothelial cells, miofibroblasts, and new temporary (ECM) extracellular matrix components. The intermittent ECM differs in the composition of the ECM in normal tissue and its component is derived from fibroblasts. These components include fibronectin, collagen, glycosaminoglycans, elastin, glycoproteins and proteoglycans. Its main components are fibronectin and hyaluronan, which creates a highly hydrated matrix and facilitates cell migration. Then this temporary matrix is ​​replaced by an ECM that is more similar to that found on an unscathed network.
Growth factors (PDGF, TGF-?) And fibronectin promote proliferation, migration to wound base, and ECM molecule production by fibroblasts. Fibroblasts also secrete growth factors that attract epithelial cells to the site of the wound. Hypoxia also contributes to the proliferation of fibroblasts and excretion of growth factors, although too little oxygen will inhibit the growth and deposition of ECM components, and can lead to excessive fibrosis scarring.
Collagen Deposition
One of the most important tasks of fibroblasts is the production of collagen.
Collagen deposition is important because it increases the strength of the wound; before being laid, the only one holding a closed wound is a fibrin-fibronectin clot, which does not provide much resistance to a traumatic injury. Also, the cells involved in the inflammation, angiogenesis, and connective tissue construction attach, grow and differentiate on the collagen matrix defined by fibroblasts.
Collagen type III and fibronectin generally begin to be produced in considerable quantities somewhere between about 10 hours and 3 days, depending mainly on the size of the wound. Deposits deposition them at one to three weeks. They are the tensile substance that dominates until the final phase of maturation, where they are replaced by stronger type I collagen.
Even when fibroblasts produce new collagen, collagenase and other factors lower it. Shortly after injury, synthesis exceeds degradation so that the level of collagen in the wound increases, but then the production and degradation become the same so no net collagen gain. This homeostasis marks the beginning of the next ripening phase. Granulation gradually stops and fibroblasts are reduced in number in wounds once their work is done. At the end of the granulation phase, fibroblasts begin apoptosis, transforming the granulation tissue from the cell-rich environment into cells that are primarily composed of collagen.
Epithelialization
The formation of granulation tissue into open wounds allows the phase of reepithelialization to take place, the epithelial cells migrating across the new tissue to form a barrier between the wound and the environment. Basal keratinocytes from the edges of the wound and skin such as hair follicles, sweat glands, and oil glands (oils) are the main cells responsible for the epithelial phase of wound healing. They advance in a sheet on the wound site and proliferate at the end, stopping moving when they meet in the middle. In healing that produces scars, sweat glands, hair roots and nerves are not formed. With the lack of hair follicles, the nerves and sweat glands, wounds, and healing scars are generated, it presents a challenge for the body with regards to temperature control.
Keratinocytes migrate without first proliferation. Migration can begin as early as several hours after injury. However, epithelial cells require proper tissue to migrate, so if the wound is deep, it should be filled first with granulation tissue. Thus the start time of migration varies and can occur about one day after the wound. Cells on the edges of the wound multiply on the second and third post-wound days to provide more cells for migration.
If the basement membrane is not violated, the epithelial cells are replaced within three days by division and migration into cells in the basal stratum in the same way that occurs on the unharmed skin. However, if the basal membrane is damaged at the wound site, reepithelization must occur from the wound edges and from the skin's complement like hair follicles and sweat and oil glands that enter the dermis coated with a proper keratinocyte. If the wound is very deep, the skin complement can also be damaged and migration can only occur from the edge of the wound.
The migration of keratinocytes over the site of the wound is stimulated by a lack of contact inhibition and by chemicals such as nitric oxide. Before they begin to migrate, the cells must dissolve their desmosomes and hemidesmosomes, which usually anchors cells with intermediate filaments in their cytoskeleton to other cells and to the ECM. The transmembrane receptor protein is called integrin, made of glycoproteins and usually anchors cells to the basement membrane by the cytoskeleton, released from the intermediate filament of the cell and moves to the actin filament to serve as an attachment to the ECM for pseudopodia during migration. Thus keratinocytes escape from the basement membrane and may enter the wound bed.
Before they begin to migrate, keratinocytes change shape, become longer and more flat and extend cellular processes such as lamellipodia and a wide process that looks like ruffles. Actin filaments and pseudopodia forms. During migration, the integrins on the pseudopod are attached to the ECM, and actin filaments in the projection draw together cells. Interactions with molecules in ECM through integrins further promote the formation of actin filaments, lamellipodia, and filopodia.
Epithelial cells climb to each other to migrate. These growing epithelial cells are often called epithelial tongues. The first cells attached to the basement membrane form the basal stratum. These basal cells continue to migrate across the wound bed, and the epithelial cells above them also slide. The faster this migration takes place, the less scarring there is.
Fibrin, collagen, and fibronectin in ECM can then signal cell to divide and migrate. Like fibroblasts, migrating keratinocytes use crosslinked fibronectin with fibrin deposited in inflammation as an attachment site to be crawled.
When keratinocytes migrate, they move above the granulation tissue but remain under the scab, thus separating the scab from the underlying tissue. Kerokans are formed in locations affected by harmful UVR and the main biological function of human scabs wounds is to inhibit UVR exposure, thus protecting cells exposed to wounds from UVR-induced DNA damage. Epithelial cells have the ability to phagocytate debris such as dead tissue and bacterial material that will block their path. Because they have to dissolve any scab formed, keratinocyte migration is best enhanced by moist environments, since dry ones lead to larger and harder scab formation. To make their way along the network, keratinocytes must dissolve the clots, debris, and parts of the ECM to get through. They secrete plasminogen activators, which activate plasminogen, converting it into plasmin to dissolve the scab. Cells can only migrate to living tissue, so they should excrete collagenases and proteases such as metalloproteinase matrices (MMPs) to dissolve the damaged ECM parts in their way, especially on the front of the sheets that migrate. Keratinocytes also dissolve the basement membrane, instead using a new ECM made by fibroblast to be crawled.
As keratinocytes continue to migrate, new epithelial cells must be formed at the edges of the wound to replace them and to provide more cells for the advanced sheet. The proliferation behind migrating keratinocytes usually begins a few days after injury and occurs at a rate that is 17 times higher in epithelial stage than in normal tissue. Until the entire wound area reappears, the only proliferating epithelial cells are on the edge of the wound.
Growth factors, stimulated by integrins and MMP, cause cells proliferate at the edges of the wound. Keratinocytes themselves also produce and excrete factors, including growth factors and basement membrane proteins, which help both in epithelialization and other healing phases. Growth factors are also important for the immune defense of skin lesions by stimulating the production of antimicrobial peptides and neutrophil chemotactic cytokines in keratinocytes.
Keratinocytes continue to migrate throughout the wound bed until cells from both sides meet in the middle, where point inhibition contact causes them to stop migrating. When they have finished migrating, keratinocytes secrete proteins that form new basal membranes. Cells reverse the morphological changes they experience to begin migrating; they rebuild the desmosomes and hemidesmosomes and return anchored to the basement membrane. Basal cells begin to divide and differentiate in the same way as in normal skin to rebuild the strata found on the reepitelial skin.
Contraction
Contraction is the key phase of wound healing with improvement. If the contractions last too long, contractions can cause damage and loss of function. Thus there is a great interest in understanding the biology of wound contraction, which can be modeled in vitro using a collagen gel contraction test or a dermal equivalent model.
Contractions begin about a week after injury, when fibroblasts have differentiated into miofibroblasts. In wounds with full thickness, peak contractions in 5 to 15 days post injury. Contractions may last for several weeks and continue even after the wound is completely reepitelial. Large wounds can be 40 to 80% smaller after contractions. The wound can contract at a rate of up to 0.75 mm per day, depending on how loose the tissue is in the wounded area. Contractions usually do not occur symmetrically; more wounds have a 'contraction shaft' that allows for larger organizations and cell alignment with collagen.
Initially, contractions occur without myofibroblast involvement. Then, fibroblasts, stimulated by growth factors, differentiate into miofibroblasts. Myofibroblasts, which are similar to smooth muscle cells, are responsible for contractions. Myofibroblasts contain the same type of actin as found in smooth muscle cells.
Myofibroblasts are attracted by fibronectin and growth factors and they move along fibronectin associated with fibrin in the ECM while to reach the edges of the wound. They form connections to the ECM at the edges of the wound, and they attach to each other and to the edge of the wound by the desmosomes. Also, in adhesion called fibronexus, actin in myofibroblasts is linked through cell membranes to molecules in extracellular matrices such as fibronectin and collagen. Myofibroblasts have many such adhesions, allowing them to pull the ECM when they contract, reducing the size of the wound. In this part of the contraction, closure occurs faster than in the first, myofibroblast-independent.
When actin is in the myofibroblast contract, the wound edges are pulled together. Fibroblasts put collagen to strengthen the wound during myofibroblast contract. The contraction phase in proliferation ends when the myofibroblasts stop contracting and apoptosis. Temporary matrix damage leads to decreased hyaluronic acid and increased chondroitin sulfate, which gradually triggers fibroblasts to stop migrating and multiplying. These events mark the beginning of the maturation stage of wound healing.
Maturation and remodeling
When the level of collagen production and degradation equates, the maturation phase of tissue repair is said to have begun. During ripening, collagen type III, which is prevalent during proliferation, is replaced by type I collagen. Initially unorganized collagen fibers are rearranged, crossed, and aligned along the line of stress. The beginnings of the maturation phase may vary widely, depending on the size of the wound and whether it is initially covered or left open, ranging from about 3 days to 3 weeks. The maturation phase may last for a year or longer, also depending on the type of wound.
As the phase progresses, the tensile strength of the wound increases. Collagen will reach about 20% of its tensile strength after 3 weeks, rising to 80% at week 12. The maximum scar strength is 80% of unrefined skin. Because the activity at the wound site is reduced, the scar loses its red appearance because the blood vessels that are no longer needed are removed by apoptosis.
The wound healing phase usually develops in a predictable and timely manner; if not, healing may develop improperly in either chronic wounds such as venous ulcers or pathologic scarring such as keloid scars.
Factors affecting wound healing
Many factors that control the efficacy, speed, and way of wound healing are under two types: local and systemic factors.
Local factors
- Humidity; keeping the wound moist than dry makes wound healing faster and with less pain and reduces scarring
- Mechanical factors
- Edema
- Ionizing radiation
- Technique of wound closure
- Ischemia and necrosis
- Foreign body. Sharp, small foreign objects can penetrate the skin leaving little surface injuries but causing internal injuries and internal bleeding. For a foreign body of glass, "often, innocent skin wounds disguise the wounded nature beneath it". First-degree nerve injury takes several hours to several weeks to recover. If a foreign body passes through a nerve and causes a first-degree nerve injury during admission, foreign body sensations or internal injuries can be delayed several hours to several weeks after admission. The sudden increase of pain during the first few weeks of wound healing can be a sign of nerve recovery that reports an internal injury rather than a newly developed infection.
- Low oxygen tension
- Perfusion
Systemic factors
- Inflammation
- Diabetes - Individuals with diabetes exhibit reduced abilities in acute wound healing. In addition, individual diabetes is susceptible to developing chronic diabetic foot ulcers, a serious complication of diabetes that affects 15% of people with diabetes and accounts for 84% of all diabetes-related lower leg amputations. Impaired healing ability of diabetics with diabetic foot ulcers and/or acute lesions involves several pathophysiological mechanisms. This disturbed healing involves hypoxia, fibroblast and epidermal cell dysfunction, angiogenesis and neovascularization disorders, high levels of metalloproteases, damage from reactive oxygen species and AGEs (late glycemic end products), decreased host immune resistance, and neuropathy.
- Nutrition - Malnutrition or nutritional deficiency has a recognizable effect on wound healing post trauma or surgical intervention. Nutrition including proteins, carbohydrates, arginine, glutamine, polyunsaturated fatty acids, vitamin A, vitamin C, vitamin E, magnesium, copper, zinc and iron all play an important role in wound healing. Fats and carbohydrates provide most of the energy needed for wound healing. Glucose is the most prominent fuel source used to make cellular ATP, providing energy for angiogenesis and new tissue deposition. Because the nutritional needs of each patient and its associated lesions are complex, it is suggested that tailored nutrition support will be beneficial both for acute and chronic wound healing.
- Metabolic Disease
- Immunosuppression
- Connective network disruption
- Smoking Smoking causes delays in the speed of wound repair especially in the proliferative and inflammatory phases. It also increases the likelihood of certain complications such as broken wounds, wounds and flap necrosis, decreased tensile strength of the wound and infection.
- Age - Increased age (over 60 years) is a risk factor for the healing of the affected wound. It is known that, in older adults of overall good health, the effects of aging cause a temporary delay in healing, but there is no great damage with respect to the quality of healing. Delayed wound healing in elderly patients is associated with an altered inflammatory response; eg delayed T-cell infiltration of wounds with changes in chemokine production, and reduced macrophage phagocytic capacity.
- Alcohol - Alcohol consumption damages wound healing and also increases the chance of infection. Alcohol affects the proliferative healing phase. One unit of alcohol causes negative effects on re-epithelization, wound closure, collagen production and angiogenesis. Research and development
- Examples of major intentions include: well-repaired lacerations, reduction of bone fractures, healing after flap surgery.
- Secondary intentions are implemented when primary intentions are not possible.
- This is caused by injuries caused by major trauma where there is significant tissue loss or tissue damage.
- The wound is allowed to granulate.
- The surgeon can package the wound with gauze or use a drainage system.
- Granulation produces a wider scar.
- The healing process can be slow due to drainage from infection.
- Wound care should be done daily to encourage cleansing of wound debris to allow for the formation of granulation tissue.
- Using antibiotics or antiseptics for surgical wound healing with secondary intentions is controversial.
- Examples: gingivectomy, gingivoplasty, tooth extraction socket, severe fracture, burns, severe injury, compressive ulcers.
- The wound was initially cleared, braced and observed, typically 4 or 5 days before closing.
- The injuries are intentionally left open.
- Example: wound healing by using network transplant.
- The formation of deficient scars: The result of wound dehiscence or rupture of the wound due to inadequate formation of granulation tissue.
- Excessive scar formation: Hypertrophic scars, keloid, desmoid.
- Excessive milling (proud meat).
- Contraction of deficiency (in skin grafts) or excessive contraction (on burns).
- Other: Dystrophic calcifications, pigment changes, painful scars, incisional hernia
- Marjolin ulcer
- Infection Biologics, _skin_substitutes, _biomembranes_and_scaffolds "> Biological, skin substitute, biomembrane, and scaffold
- Shared cell migration
- Dress up (medically)
- History of wound care
- Regeneration in humans
- Wound preparation
- Injuries
- Healing is scar-free
- Wound Repair and Regeneration Official publication of the European Wound Healing Institute and Network Improvement Agency.
- Burn and Wound Journal
- Fibrogenesis & amp; Tissue Repair, an online open access journal about chronic wound healing and fibrogenesis.
- EWMA Journal , Journal of the European Wound Management Association
- Ostomy Wound Management The official journal of the Association for the Advancement of Wound Care.
Until around 2000, the classical paradigm of wound healing, involving stem cells limited to organ-specific lines, was never seriously challenged. Since then, the idea of ​​adult stem cells that have cellular plasticity or the ability to differentiate into non-hereditary cells has emerged as an alternative explanation. To be more specific, hematopoietic progenitor cells (which cause mature cells in the blood) may have differentiated capabilities back to hematopoietic stem cells and/or transdifferentiate into non cells - lineage, such as fibroblasts.
Stem cell and cellular plasticity
Multipotent adult stem cells have the capacity to renew themselves and give rise to different cell types. Stem cells produce progenitor cells, which are cells that do not renew themselves, but can produce several cell types. The degree of stem cell involvement in skin wound healing (skin) is complex and not fully understood.
It is thought that the epidermis and dermis are reshaped by active stem cells located at the top of the rete ridges (basal cell or BSC), hair follicle bulges (hair follicle stem cells or HFSC), and papillary dermis. In addition, bone marrow also contains stem cells that play a major role in healing skin wounds.
In rare circumstances, such as extensive skin injuries, a subpopulation of self-renewal in the bone marrow is induced to participate in the healing process, where they induce cells that secrete collagen that seem to play a role during wound repair. These two self-renewal subpopulations are (1) bone marrow mesenchymal stem cells (MSC) and (2) hematopoietic stem cells (HSC). Bone marrow also stores subgroup progenitors (endothelial progenitor cells or EPCs) which, in the same type of arrangement, are mobilized to aid in the reconstruction of blood vessels. In addition, he thinks that, extensive injury to the skin also increases the initial trade of a unique subclass of leukocytes (circulating fibrocytes) to the injured site, where they perform various functions related to wound healing.
Repair wound versus regeneration
Injury is a morphological disorder and/or a certain tissue functionality. After injury, structural tissue heals with incomplete or complete regeneration. In fact, the network without interference in morphology almost always really regenerate. An example of complete regeneration without morphological disorders is the unharmed tissue, such as the skin. Uninjured skin has sustained replacement and cell regeneration that always results in complete regeneration.
There is a subtle difference between 'repair' and 'regeneration'. Repair means incomplete regeneration . Improvement or incomplete regeneration refers to the physiological adaptation of organs after injury in an attempt to rebuild continuity without regard to the proper replacement of lost or damaged tissue. true network regeneration or complete regeneration , refers to replacement of lost/damaged tissue with 'proper' copies, so that both morphology and functionality are completely restored. Although after an injured mammal can regenerate completely spontaneously, they usually do not fully regenerate. Examples of tissues that regenerate completely after morphological disorders are endometrium; endometrium after the damage process through the menstrual cycle heals with complete regeneration.
In some cases, after tissue damage, such as on the skin, regeneration closer to complete regeneration can be induced by the use of biodegradable scaffolds (collagen-glycoaminoglycans). The scaffold is structurally analogous to the extracellular matrix (ECM) found in the normal/unharmed dermis. Interestingly, the fundamental conditions necessary for tissue regeneration often oppose conditions favorable to efficient wound repair, including inhibition of platelet activation, (2) inflammatory responses, and (3) wound contractions. In addition to providing support for fibroblasts and endothelial cell enclosures, biodegradable scaffolds inhibit wound contraction, thus allowing the healing process to lead to more-regenerative/less-scarred pathways. Pharmaceutical agents have been investigated that may be able to kill myofibroblast differentiation.
The new way of thinking comes from the idea that heparan sulfate is a key player in tissue homeostasis: a process that makes tissue replace dead cells by identical cells. In the wound area, tissue homeostasis is lost when the degraded heparan sulfate prevents the replacement of dead cells by identical cells. The heparan sulfate analogs can not be degraded by all heparanases and glycanases and bind to the heparin-free sulfate bonds in ECM, thus maintaining normal tissue homeostasis and preventing scarring.
Improvement or regeneration is associated with hypoxia-inducible 1-alpha factor (HIF-1a). Under normal circumstances after HIF-1a injury is degraded by prolyl hydroxylase (PHDs). The scientists found that simple up-regulation of HIF-1a through PHD inhibitors regenerates lost or damaged tissue in mammals that have an improved response; and continued-down regulation of Hif-1a results in healing with scarring responses in mammals with previous regenerative responses to tissue loss. The act of setting up HIF-1a can turn off, or turn on the mammalian key regeneration process.
Wound healing without scars
Healing wound without an eyelid is a concept based on healing or repair of skin (or tissues/other organs) after injury with the goal of healing with subjective scarring and relatively less than is normally expected. Uncovered healing sometimes mixes with the concept of scar-healing, which is a wound healing that does not produce scar ( free from scar tissue). But they are a different concept.
A reversed wound healing for without scar is scarification (wound healing for more scars). Historically, certain cultures regard attractive scarification; However, this is generally not the case in modern western societies, where many patients turn to plastic surgery clinics with unrealistic expectations. Depending on the type of scar, treatment may be invasive (intralesional steroid injections, surgery) and/or conservative (compression therapy, topical silicone gel, brachytherapy, photodynamic therapy). Clinical assessment is needed to successfully balance the potential benefits of various treatments available against possible poor response and possible complications resulting from this treatment. Many of these treatments may have only a placebo effect, and the evidence base for many current treatments is poor.
Since the 1960s, an understanding of the basic biological processes involved in wound repair and tissue regeneration has evolved due to advances in cellular and molecular biology. Currently, the ultimate goal in wound management is to achieve rapid wound closure with functional tissues that have minimal aesthetic scar tissue. However, the ultimate goal of wound healing biology is to induce a more complete reconstruction of the wound area. Wound healing only occurs in mammalian fetal tissue and complete regeneration is restricted to lower vertebrates, such as salamanders and invertebrates. In adult humans, injured tissue is repaired by collagen precipitation, collagen remodeling and scar formation, where fetal wound healing is believed to be more than a regenerative process with minimal or absent scarring. Therefore, fetal wound healing can be used to provide a model of mammals that can be accessed from the optimal healing response in adult human tissue. The guidance on how this can be achieved comes from the study of wound healing in embryos, where improvements are rapid and efficient and result in perfect regeneration of lost tissues.
Etymology wound healing without a trace has a long history. In ancient healing concepts healing without a trace was raised early in the 20th century and appears in a paper published in the London Lancet. This process involves cutting in the slope of the surgery, not the right angle...; it was explained in various newspapers.
Wound healing simulation from a growth perspective
Sufficient effort has been devoted to understanding the physical relationships that regulate wound healing and subsequent scarring, with mathematical models and simulations developed to explain these relationships. The growth of tissue around the wound site is the result of cell migration and the deposition of collagen by these cells. Collagen alignment describes the level of scar tissue; collagen-bending collagen weave is a characteristic of normal skin, whereas collagen fibers parallel lead to significant scarring. It has been shown that tissue growth and scar formation levels can be controlled by modulating stress at the wound site.
Growth of tissue can be simulated using the relationship from biochemical and biomechanical point of view. Biologically active chemicals that play an important role in wound healing are modeled by Fickian diffusion to produce concentration profiles. The equilibrium equation for open systems when wound healing modeling combines mass growth due to cell migration and proliferation. Here the following equation is used:
D t ? 0 = Div (R) R 0 ,
where ? represents the mass density, R represents the mass flux (from cell migration), and R 0 represents the source of mass (from cell proliferation, division, or enlargement).
Intent to wound closure
Successful wound healing depends on different types of cells, molecular mediators and structural elements.
The main intention
The main goal is the healing of clean wounds without loss of tissue. In this process, the ends of the wound are put together, so they are adjacent to each other (recalculated). Closure of the wound is done by stitching (sutures), staples, or adhesive tape or glue.
Primary intentions can only be implemented when the wound is appropriate and there is minimal disturbance to the local tissues and epithelial basement membrane, eg surgical incision.
This process is faster than healing with secondary intentions. There is also less scarring associated with the main intention, because there is no large network losses to be met with granulation tissue. (Primary intentions do require some granulation tissue to form.)
Secondary intentions
tertiary intention
(Pending primary or secondary seam delay):
If the ends of the wound are not immediately re-diagnosed, the delay of primary wound healing occurs. This type of healing may be desirable in cases of contaminated wounds. On the fourth day, contaminated tissue phagocytosis goes well, and epithelial processes, collagen deposition, and maturation occur. The foreign material is closed by macrophages that can morpheme into epithelioid cells, which are surrounded by mononuclear leucocytes, forming granulomas. Usually the wound is closed surgically at this time, and if the "cleansing" of the wound is incomplete, chronic inflammation may occur, producing prominent scar tissue.
Overview of growth factors involved
Here are the major growth factors involved in wound healing:
Wound healing complications
Many major complications:
Advances in clinical understanding of their wounds and pathophysiology have ordered significant biomedical innovations in the treatment of acute, chronic, and other types of injuries. Many biologists, skin substitutes, biomembranes and scaffolds have been developed to facilitate wound healing through various mechanisms. 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.
See also
Notes and references
External links
Source of the article : Wikipedia
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