Year : 2019 | Volume
: 3 | Issue : 2 | Page : 50--59
A review on wound healing
MG Visha1, Monika Karunagaran2,
1 Department of Pathology, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
2 Department of Oral Pathology, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
Department of Oral Pathology, Saveetha Dental College, Saveetha University, 162, Poonamalle High Road, Velapanchavadi, Chennai - 600 077, Tamil Nadu
A wound is disruption of the anatomic structure and its useful continuity of residing tissue. Healing is the system of repair that follows damage to the skin and other soft tissues. Wound recovery is basically, a survival mechanism to restore shape and feature. The ability of a wound to heal depends partly on its intensity, as well as on the general fitness and dietary status of the man or woman. Clinically, wound may be categorized as acute or persistent primarily based at the timeliness of recuperation. The intense wound is a breakdown of the integrity of the gentle tissue envelope surrounding any part of the frame. Chronic wound is described, as ones wounds that fail to progress through orderly and timely sequence of restore or wounds that bypass through the restore system without restoring anatomic and useful effects. Although some additives of the recovery process have regenerative elements, pores and skin are the example of tissues in which the response to injury is predominantly certainly one of repair. Phases of wound healing are hemostasis, irritation, proliferation, epithelization, and maturation remodeling.
|How to cite this article:|
Visha M G, Karunagaran M. A review on wound healing.Int J Clinicopathol Correl 2019;3:50-59
|How to cite this URL:|
Visha M G, Karunagaran M. A review on wound healing. Int J Clinicopathol Correl [serial online] 2019 [cited 2020 Sep 20 ];3:50-59
Available from: http://www.ijcpc.org/text.asp?2019/3/2/50/272729
Tissue Repair and Process of Wound Healing
Wound healing is an intricate process in which the tissue repairs itself after injury. It is a process that involves the activation of intercellular pathways, coordination of tissue integrity, and homeostasis. Depending on the nature and depth of the injury, the wound healing can be classified. The acute wound is a breakdown of the integrity of the soft-tissue envelope surrounding any portion of the body. Acute wound is defined by its size, depth, and involved anatomic structures. The duration of healing and the differentiation between acute and chronic is quite uncertain and varies based on the site and cause of the wound, age, and physical condition of the patient. The time course between an acute versus chronic wound is 4 and 6 weeks. It is during this time that if an acute wound has not healed spontaneously, then it is likely to become chronic.
Tissue repair is a simple linear process, in which the growth factors cause cell proliferation, thus leading to an integration of dynamic changes that involve soluble mediators, blood cells, the production of the extracellular matrix (ECM), and the proliferation of parenchymal cells., Wound healing is a natural biological process that is a combination of a series of independent processes where dermal cells and epidermal cells, ECM, plasma-derived proteins, growth factors, and cytokines all act together to initiate wound healing.,, Wound healing is divided into four phases: the hemostasis phase, the inflammatory phase, the proliferation phase, and the remodeling phase. Other categories of wound healing are primary healing, delayed primary healing, and healing by secondary intention. Even though different categories exist, the interactions of cellular and extracellular constituents are similar.
Phases of Wound Healing
This phase entails a sequence of complex reactions, mainly hemostasis and clot formation. The clot includes a fibrin mesh with aggregated platelets embedded in it. The mesh traps crimson red cells that are the major factor of the clot plug. Fibrin is the cease manufactured from the coagulation cascades which can be stimulated by means of vascular injuries. There is an intrinsic and an extrinsic coagulation cascade brought on by using separate events. Activation of Factor XII initiates the intrinsic coagulation pathway and happens when blood is exposed to foreign surfaces. Publicity to tissue component that binds component VII initiates the extrinsic coagulation pathway. Tissue issue is not observed on vascular endothelial cells but is determined in abundance on extravascular cellular surfaces, especially on adventitial fibroblasts. On injuring to the cells, the aspect is released. Both coagulation pathways result in the manufacturing of thrombin catalyzing the conversion of fibrinogen to fibrin.
Similarly to contributing to hemostasis, fibrin is also the primary thing of the provisional matrix that bureaucracy within the wound in the course of the early recovery period. Fibronectins are a class of glycoproteins that facilitate attachment of migrating cells onto the fibrin latticework and they are an exceptionally crucial thing of the early matrix in addition to the mature dermis., Fibronectin is produced by way of fibroblasts and epithelial cells. Stimulation of the hemostatic mechanisms is limited to the website of injury in that normal endothelial cells produce prostacyclin that inhibits platelet aggregation. Similarly, in uninjured regions, antithrombin III binds thrombin and bounds its pastime and protein C degrades factors V and VII., The tactics of blood coagulation and platelet aggregation terminate while the stimuli for clot initiation use up. Clot breakdown starts as quickly as the clots form. Plasminogen activator mediates the clot lysis and converts plasminogen to plasmin, an exceedingly effective enzyme which can degrade an extensive style of ECM proteins.
In a vascular anti-inflammatory reaction, the lesioned blood vessels contract and the leaked blood coagulate contributing to the protection of its integrity. The coagulation includes an aggregation of thrombocytes and platelets in a fibrin community, relying on the action of unique factors through the activation and aggregation of those cells. The fibrin community further to reestablishing homeostasis and forming a barrier toward the invasion of microorganisms, organizes the necessary temporary matrix for cellular migration which in turn restores the skins function as a protecting barrier preserving the skins integrity. This also makes it viable for mobile migration to the lesions microenvironment and the stimulation of fibroblast proliferation. Response within the anti-inflammatory level is characterized through the influx of leukocytes in the wound vicinity. This type of response could be very short and coincides with the important thing signs and symptoms of inflammation, which are revealed with the aid of the edema and the erythema at the place of the lesion. In general, cellular response is established inside the first 24 h and might increase for up to 2 days.
A quick activation of the immune cells within the tissue may arise as takes place with astrocytes, gamma-delta cells, and Langerhans cells, which secrete chemokines and cytokines. Infection is a localized and protective tissue response; this is unleashed with the aid of the lesion, inflicting tissue destruction. Inflammatory cells play a vital position in wound recovery and contribute to the release of lysosomal enzymes and reactive oxygen species (ROS), as well as facilitate the smooth-up of various mobile particles., According to a study, Buckley argues that the interaction of leukocytes and stromal cells at some stage in an acute anti-inflammatory reaction resolves across the anti-inflammatory awareness. Neutrophils are known for expressing many pro-anti-inflammatory cytokines and a huge amount of fantastically active antimicrobial substances, including ROS, cationic peptides, and proteases on the vicinity of the lesion. The anti-inflammatory reaction continues with the energetic recruitment of the neutrophils in response to the activation of the supplement gadget, platelet degranulation, and bacterial degradation. These are attracted through many anti-inflammatory cytokines produced via activated platelets, endothelial cells, and degradation products of pathogenic marketers. Nine on this way, the neutrophils are the number one activated and recruited cells that play a function within the easy-up of the tissue, in addition to contribute to the death of invading marketers.
Only some hours after the lesion, an amount of neutrophils transmigrate via the endothelial cells present in the blood capillary walls, which might be activated with the aid of pro-anti-inflammatory cytokines, such as interleukin-1 (IL-1) β, tumor necrosis element-alpha (TNF-α), and interferon-gamma at the place of the lesion. Such cytokines promote the expression of many training of adhesion molecules. These adhesion molecules are a determining factor for the diapedesis of neutrophils, such as selectins and integrins, which have interaction with those already present at the membrane surface of endothelial cells. The referent cells also have an effect on many different factors of tissue repair, which include the decision of fibrin and ECM coagulation, the prompting of angiogenesis, and reepithelialization. As of 48 h after the onset of the lesion, the migration of monocytes from neighboring blood vessels, which also infiltrate the lesion vicinity, is intensified, and with the era of the brand new genic expression profiles, are differentiated into macrophages. Those, which can be activated through chemokine signaling, can act as cells that gift antigens and useful resource neutrophils in phagocytosis. As a result, in addition to resident macrophages, the principle population of macrophages inside the lesion is recruited from the blood in response to chemotactic products, as may be seen in ECM protein fragments, transforming growth factor-beta (TGF-β), and MCP-1. Based on the profiles of genic expression, macrophages may be classified as classically activated M1 and M2.
These macrophages launch increase elements, together with platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), which are generally necessary for the triggering and propagation of latest tissue within the lesioned area, in view that animals with a depletion of macrophages gift defects in wound restore, conferring upon those cells a key function inside the transition of the exudative degree to the proliferative degree inside the tissue restore system. Macrophages carry out the features of muscular debris phagocytosis, in addition to the manufacturing and launch of cytokines and pro-angiogenic, anti-inflammatory, and fibrogenic elements, and of free radicals. The macrophages upon secreting chemotactic factors, entice different anti-inflammatory cells to the wound location. Addition, they produce prostaglandins, which function as strong vasodilators, affecting the permeability of microblood vessels. Together, such elements purpose the activation of endothelial cells. those cells, according to Mendonça and Coutinho-Netto, also produce PDGF, TGF-β, fibroblast growth factor (FGF), and VEGF, which stand out as the primary cytokines capable of stimulating the formation of granulation tissue.
This segment is composed of different subphases. Those subphases do no longer appear in discrete time frames but constitute a usual and ongoing technique. The subphases are “fibroplasia, matrix deposition, angiogenesis, and reepithelialization.” In days 5–7, fibroblasts have migrated into the wound, laying down new collagen of the subtypes I and III. Early in normal wound recovery, kind III collagen predominates but is later changed by using kind I collagen. Tropocollagen is the precursor of all collagen kinds and is converted within the mobile's tough endoplasmic reticulum, where proline and lysine are hydroxylated. Disulfide bonds are installed, allowing three tropocollagen strands to form a triple left-handed triple helix, termed procollagen. As the procollagen is secreted into the extracellular space, peptidases within the cell wall cleave terminal peptide chains, growing genuine collagen fibrils. The wound is suffused with GLycosAminoGlycans (GAGs) and fibronectin produced via fibroblasts.
Those GAGs include heparan sulfate, hyaluronic acid, chondroitin sulfate, and keratan sulfate. Proteoglycans are GAGs that are bonded covalently to a protein core and make contributions to matrix deposition. Angiogenesis is made from determining vessel offshoots. The formation of recent vasculature calls for ECM and basement membrane degradation accompanied by means of migration, mitosis, and maturation of endothelial cells. Primary FGF and vascular endothelial growth components are believed to modulate angiogenesis. Reepithelization takes place with the migration of cells from the periphery of the wound and adnexal structures. This technique commences with the spreading of cells inside 24 h. Department of peripheral cells happens in hours 48–72, resulting in a thin epithelial cellular layer, which bridges the wound. Epidermal boom elements are believed to play a key role in this factor of wound recovery. This succession of subphases can last up to 4 weeks inside the easy and uncontaminated wound.
Phase 4-Remodeling phase
The 1/3 section of healing includes reworking, which begins 2–3 weeks after the onset of the lesion and might final for 12 months or greater. The middle intention of the remodeling stage is to reap the maximum tensile electricity via reorganization, degradation, and resynthesize of the ECM. In this very last level of the lesion's restoration, a try to get better the normal tissue structure occurs, and the granulation tissue is progressively revamped, forming scar tissue that is much less cellular and vascular 3 and that exhibits a progressive growth in its attention of collagen fibers. This segment involves remodeling of collagen from kind III to type I. Cellular interest reduces and the variety of blood vessels in the wounded area regress and decrease. After the 3rd week, the wound undergoes steady changes, known as transforming that could remaining for years after the preliminary injury passed off. Collagen is degraded and deposited in an equilibrium-generating style, resulting in no exchange in the amount of collagen gift within the wound. The collagen deposition in normal wound recovery reaches a height through the 0.33 week after the wound is created. Contraction of the wound is an ongoing process ensuing in elements from the proliferation of the specialized fibroblasts termed my fibroblasts, which resemble contractile smooth muscle cells. Wound contraction takes place to a more quantity with secondary recovery than with number one healing. Maximal tensile strength of the wound is completed by way of the 12th week, and the ultimate resultant scar has best 80% of the tensile strength of the authentic skin that it has replaced.
Factors Affecting Wound Healing
Multiple variables can lead to impeded wound healing. In common terms, the components that impact repair can be categorized into local and systemic. Local components are those that specifically impact the characteristics of the wound itself, while systemic components are generally the well-being or illness state of the person that influences his or her capacity to repair. Numerous of these components are related, and the systemic variables act through the nearby impacts influencing wound healing.
Local components affecting wound healing
Oxygen is imperative for cell digestion system, particularly vitality generation by implies of adenosine tri phosphate and is basic for about all wound-healing forms. It avoids wounds from disease, actuates angiogenesis, increments keratinocyte separation, movement, and reepithelialization, upgrades fibroblast multiplication and collagen amalgamation, and advances wound compression. Further, the level of superoxide (O2) production (a key element for oxidative killing pathogens) through polymorphonuclear leukocytes is significantly dependent on oxygen ranges. In wounds, wherein oxygenation is not restored, restoration is impaired. Brief hypoxia after injury triggers wound restoration, however, prolonged or chronic hypoxia delays wound recuperation. In acute wounds, hypoxia serves as a sign that stimulates many elements of the wound-recuperation technique.
Hypoxia can setoff cytokine and growth issue manufacturing from macrophages, keratinocytes, and fibroblasts. Cytokines that are produced in reaction to hypoxia include PDGF, TGF-β, VEGF, tumor necrosis component-α (TNF-α), and endothelin-1 and are essential promoters of mobile proliferation, migration and chemotaxis, and angiogenesis in wound healing. In normally healing wounds, ROS inclusive of hydrogen peroxide and O2 are notion to act as cellular messengers to stimulate key strategies related to wound restoration, including cellular motility, cytokine movement (which includes PDGF signal transduction), and angiogenesis. Each hypoxia and hyperoxia growth ROS production, but a multiplied degree of ROS transcends the beneficial effect and reasons extra tissue damage.
Once the skin is harmed, microorganisms that are ordinarily sequestered at the skin surface get to the basic tissues. The state of disease and replication status of the microorganisms decides whether the wound is classified as having defilement, colonization, local infection/critical colonization, and/or spreading intrusive disease. Defilement is the nearness of nonreplicating life forms on a wound, while colonization is characterized as the nearness of duplicating microorganisms on the wound without tissue harm. Nearby infection/critical colonization is a middle of the road organize, with microorganism replication and the starting of nearby tissue reactions. Obtrusive contamination is characterized as the nearness of reproducing life forms inside a wound with ensuing has damage.
It is a normal part of the wound-recovery process and is vital to the removal of contaminating microorganisms. In the absence of effective decontamination, however, infection may be prolonged, on the grounds that microbial clearance is incomplete. Each bacteria and endotoxins can result in the prolonged elevation of seasoned-inflammatory cytokines such as IL-1 and TNF-α and elongate the inflammatory section. If this maintains, the wound may additionally input a chronic country and fail to heal. This prolonged irritation additionally ends in a multiplied degree of matrix metalloproteases, an own family of proteases which could degrade the ECM. In tandem with the increased protease content, a decreased degree of the obviously occurring protease inhibitors takes place. This shift in protease balance can motive boom elements that appear in continual wounds to be swiftly degraded. Just like different infective processes, the bacteria in infected wounds arise inside the form of biofilms, which can be complex groups of aggregated microorganism embedded in a self-secreted extracellular polysaccharide matrix.
Mature biofilms broaden protected microenvironments and are extra resistant to traditional antibiotic remedy. Staphylococcus aureus, Pseudomonas aeruginosa, and β-hemolytic streptococci are commonplace bacteria in infected and clinically noninfected wounds. P. aeruginosa and Staphylococcus appear to play an important function in bacterial contamination in wounds. Many chronic ulcers probably do now not heal due to the presence of biofilms-containing P. aeruginosa, consequently protecting the bacteria from the phagocytic hobby of invading polymorphonuclear neutrophils. This mechanism might also explain the failure of antibiotics as a treatment for continual wounds.
Systemic factors that influences wound healing
The aged population is growing quicker than any other age institution and increased age is a main chance thing for impaired wound restoration. Many scientific and animal researches at the cell and molecular degree have tested age-associated changes and delays in wound recovery. It is typically recognized that, in healthy older adults, the effect of getting old reasons a temporal postpone in wound recuperation, however, no longer real impairment in phrases of the fine of recovery. Not on time, wound healing in the aged is related to an altered inflammatory response, such as delayed T-cells infiltration into the wound place with changes in chemokine manufacturing and decreased macrophage phagocytic capability. Delayed reepithelialization, collagen synthesis, and angiogenesis have additionally been found in elderly mice compared with younger mice. Universal, there are worldwide differences in wound healing among young and aged people. A evaluation of the age-associated adjustments in healing capacity demonstrates that each section of recovery undergoes characteristic age-related changes, consisting of improved platelet aggregation, expanded secretion of inflammatory mediators, behind schedule infiltration of macrophages and lymphocytes, impaired macrophage function, reduced secretion of growth factors, delayed reepithelialization, delayed angiogenesis and collagen deposition, reduced collagen turnover and remodeling, and reduced wound energy.
In aged individuals, sex hormones play a role in age-associated wound-healing deficits. As compared with aged ladies, elderly males were shown to have delayed healing of acute wounds. A partial cause of that is that the woman estrogens, male androgens, and their steroid precursor dehydroepiandrosterone appear to have extensive consequences at the wound restoration technique. It was lately found that the variations in gene expression among aged male and young human wounds are nearly completely estrogenic regulated. Estrogen impacts wound recovery with the aid of regulating a diffusion of genes associated with regeneration, matrix manufacturing, protease inhibition, epidermal characteristic, and the genes frequently associated with inflammation. Studies suggest that estrogenic can improve the age-associated impairment in recuperation in both men and women, while androgens adjust cutaneous wound healing negatively.
Stress has an exceptional impact on human fitness and social conduct. Many illnesses including cardiovascular disorder, most cancers, compromised wound restoration, and diabetes are associated with stress. Several studies have shown that stress brought about disruption of neuroendocrine-immune equilibrium is consequential to fitness. The pathophysiology of strain results inside the deregulation of the immune system, mediated mainly through the hypothalamic–pituitary–adrenal and sympathetic–adrenal–medullary axes or sympathetic nervous device.
Diabetes affects hundreds of hundreds of thousands of people global. Diabetic individuals exhibit a documented impairment inside the healing of acute wounds. Furthermore, this population is susceptible to broaden continual nonrestoration diabetic foot ulcers (DFUs) are predicted to occur in 15% of all men and women with diabetes. DFUs are a critical problem of diabetes and precede 84% of all diabetes-associated lower leg amputation. The impaired recovery of each DFUs and acute cutaneous wounds in people with diabetes involves more than one complex pathophysiological mechanisms. DFUs, such as venous stasis sickness and pressure-related chronic nonhealing wounds, are always accompanied by way of hypoxia. The impaired recuperation that takes place in people with diabetes includes hypoxia, disorder in fibroblasts and epidermal cells, impaired angiogenesis and neovascularization, high stages of metalloproteases, harm from review of systems and a long time, decreased host immune resistance, and neuropathy.
Many medicinal drugs, which include the ones which intrude with clot formation or platelet feature, or anti-inflammatory responses and proliferation, have the capability to have an effect on wound restoration.
Systemic glucocorticoids (GC), that are regularly used as agents are used to inhibit wound restore through international effects and suppression of cell wound responses, together with fibroblast proliferation and collagen synthesis. Systemic steroids reason wounds to heal with incomplete granulation tissue and decreased wound contraction. GCs also inhibit manufacturing of hypoxia-inducible issue-1, a key transcriptional issue in restoration wounds. Beyond outcomes on restore itself, systemic corticosteroids might also boom the hazard of wound contamination. While systemic corticosteroids inhibit wound repair, topical utility produces pretty special results. Topical low-dosage corticosteroid treatment of chronic wounds has been located to boost up wound recovery, lessen pain and exudate, and suppress hypergranulation tissue formation in 79% of instances. While these superb results are putting, cautious monitoring is important to keep away from a capacity extended hazard of infection with prolonged use.
Nonsteroidal anti-inflammatory drugs
NonSteriodal Anti- Inflammatory Drugs (NSAIDs) together with ibuprofen are widely used for the remedy of infection and rheumatoid arthritis and for pain control. Low-dosage aspirin, due to its anti-platelet feature, is commonly used as a preventive healing for cardiovascular disorder. There are few data to signify that quicktime period NSAIDs have a bad impact on healing. The outcomes of low-dose aspirin on healing are not absolutely clean. Medical suggestions propose that, to avoid antiplatelet effects, individuals should stop NSAIDs for a time period equal to four to five times the half-life of drugs before surgical operation. As a consequence, most people of surgical patients do no longer have significant NSAID activity at the time of wound restore. The exception can be those cardiac sufferers who have to be maintained on low-dose aspirin due to the intense risk of cardiovascular events. In phrases of the topical application of NSAIDs on the surfaces of persistent wounds, the local use of ibuprofen-foam offers moist wound healing, reduces continual and temporary wound pain, and advantages chronic venous leg ulcer healing.
Most chemotherapeutic tablets are designed to inhibit cell metabolism, fast mobile division, and angiogenesis, and as a result, inhibit many of the pathways which might be crucial to appropriate wound repair. These medicines inhibit DNA, RNA, or protein synthesis, ensuing in reduced fibroplasia and neovascularization of wounds. Chemotherapeutic capsules postpone cell migration into the wound, decrease early wound matrix formation, decrease collagen manufacturing, impair proliferation of fibroblasts, and inhibit contraction of wounds. Similarly, those dealers weaken the immune features of the patients, and thereby hinder the inflammatory segment of recuperation and growth the risk of wound contamination. Chemotherapy induces neutropenia, anemia, and thrombocytopenia, as a consequence leaving wounds vulnerable to infection, inflicting much less oxygen transport to the wound, and also making sufferers vulnerable to excessive bleeding at the wound site.
Infected wounds and wounds which can be necrotic can regularly grow to be malodorous, and consequently, the motive, the infection, or the necrotic tissue must be treated to manipulate or get rid of the odor. Odors are a commonplace feature of many persistent wounds; mainly leg ulcers and fungating wounds and a few acute wounds; dehisced surgical wounds and infected annoying wounds. Malodor influences upon the patient's nutritional repute as smell accounts for 85%–90% of flavor and flavor. Activated charcoal dressings which include cliniSorb can be used to reduce wound odor. The activated charcoal presents an excessive surface location to absorb each exudate and any odor that can be present.
Maintenance of a wet wound restoration surroundings is widely typical because the perfect environment for wounds to heal. Wound fluid or exudate within the proper amount can bathe the wound with vitamins and actively cleanse the wound's surface. The quantity of exudate produced is individual to the wound, however, usually has a tendency to upward push all through the inflammatory phase and if infection is gift. A sensitive balance to keep an appropriate quantity of fluid on the wound interface desires to be finished. This can be finished with the aid of the use of contemporary dressing substances which both lock the exudate within the frame of the dressing or permit the safe passage of exudate via the dressing by means of its moisture vapor transmission price.
Wound infection is due to multiplying pathogenic microorganism which causes a response within the affected person. Infection can be systemic, causing the patient to come to be sick or local, handiest affecting the wound mattress, and surrounding tissues. At evaluation, the health-care expert has to observe for the clinical signs of infection: pain, heat, erythema, cellulitis, edema, and pyrexia, malodor, not on time healing, wound breakdown, fragile granulation tissue, immoderate exudate, and the presence of pus. Systemic wound infection can be handled with antibiotics; nearby wound contamination can be managed with antimicrobial dressings or topical antiseptics.
Depending on the nature of a wound, both acute or persistent, it' is far crucial to evaluate the wound within 24 h. Evaluation and treatment should be documented containing patient's wound length, dimension and photographs, remedy plan, diseases history, and normal food regimen plan. The most critical a part of wound healing treatment is wound care dressings.
In historic time, honey, dust, leaves, cobwebs, oil, fat, and animal dung have been used to stop bleeding and to take in exudate from the wound. Wound requires wet and smooth environment, therefore, limits its use to some extent. Meanwhile, permeable and nonocclusive gauze and cotton bandages are less expensive, reliable, and are extraordinarily absorbent. Pressure is needed to eliminate them from the wound web site which may lead to more wound trauma. Later, xenografts, allografts, and autografts became the conventional herbal skin replacement strategies for critical wound recovery purposes. There may be an excessive risk of contamination with those natural substitutes and that they fail to offer appropriate templates for pores and skin cells to develop and regenerate. Besides, donor webpage morbidity in autograft is some other factor for its restricted use in recovery pores and skin wounds.
Polymeric wound dressings
Natural polymers are extensively used to develop wound dressing materials. Such polymer templates provide means of imparting three-dimensional (3D) structures and supply bodily and chemical integrity to the cell tissue constructs.
Collagen has resemblances with the structure and COM function of human pores and skin. As a result, it's miles a suitable polymer to manufacture and design a huge form of wound dressing substances. Collagen, located abundantly in mammals, is the main protein present in ECM. It has a tough triple-stranded helical structure and bureaucracy 70%–80% of the dry pores and skin weight.
Gelatin is a protein, derived from collagen, also called denatured collagen. Not like collagen, it has low antigenicity and is inexpensive. Gelatin is used for preparation of biocompatible and biodegradable wound dressings.
Alginate is a linear branched polysaccharide which consists of (1 → four)-linked β-D-mannuronic acid and α-glucuronic acid residues. It is nonpoisonous, mucoadhesive, and pH sensitive. It forms a reversible hydrogel which acts as a 3D platform for cellular transplantation and new pores and skin formation.
Chitosan, a poly-N-acetyl-glucosaminoglycan, is the deacetylated chitin derived from crustaceans such as shrimps and crabs, the exoskeleton of bugs, invertebrates, and mobile wall of fungi. It is exceedingly biocompatible, biodegrade capable, nontoxic, nonimmunogenic, and exhibits antibacterial properties.
Cellulose is a renewable natural polymer which is abundantly available in nature is the main constituent of plant and herbal fibers such as cotton and linen. It is environment friendly, biocompatible, and degradable by way of bacteria and fungi present in the environment.
Synthetic polymers are value powerful and dependable materials which can be tailored in a unique style within the shape of fibers, mats, mesh, movies, sheaths and scaffolds to treat pores, and skin defects and wounds. Artificial polymers are often used as cross-linking or mixing sellers and are included in herbal polymers to make the latter mechanically solid. Such herbal/synthetic polymer blends act as temporary matrices to hold epidermal/dermal cells to remedy complete thickness wound.
Poly (lactide-co-glycolide) (PLGA) is a copolymer of polylactic acid and polyglycolic acid. It is a Food and Drug Administration-permitted biodegradable polymer with vast potentials in pores and skin tissue engineering. Skin substitutes prepared from PLGA are in exceptional call for due to their controlled degradation and tunable mechanical properties.
Hydrogels are artificial polymers which can be usually made from polymethyl methacrylates and polyvinyl pyrrolidine. They are insoluble and the cross-linked polymeric components to entrap water physically. Such specific appropriate hydrophilic materials can soak up and retain a large quantity of water while positioned on the wound site. Hydrogel dressings are used at the side of gauze protecting to preserve them accurately at the wound.
Complications of Wound Healing
The complicated wound healing technique may be derailed at many steps. The principle pathological troubles may be summarized as: inadequate scar formation – leading to wound dehiscence; or immoderate scar formation – both hypertrophic or “keloid” scarring contracture formation – an exaggeration of ordinary wound part contraction forming deformities. Hypertrophic scars arise while the remodeling level exists for a longer period of time and they are extracellular and greater vascular than mature scars. They are purple, raised, itchy, and smooth. They will subsequently mature and emerge as faded and flat. Such scars normally exist in areas where wound restoration has been not on time, for instance, due to contamination, or in youngsters or in which skin anxiety is high. They continue to be in the confines of the wound location itself. Keloid scars, alternatively are areas of excessive overgrowth beyond the confines of the unique wound vicinity. They are extraregularly associated with positive racial organizations, which include Afro-Carribeans. They regularly occur inside the relevant chest location, again and shoulders.
Pressure sores/bed sores
Sustained strain over bony prominences can result in the formation of pressure sores (otherwise called “mattress sores”) that may vary in severity from erythema to deep necrotic ulcers complex via osteomyelitis. Tsokos et al. word that pressure sores may be averted, to a large extent, by using the early use of chance evaluation rankings, modification of intrinsic and extrinsic patient-associated danger factors (i.e., those elements relating to frequent modifications of body role, nutrition and many others), monitoring, and prophylaxis (which includes the usage of suitable mattresses and so on). Deaths in nursing houses and hospitals, wherein issues of the appropriateness and widespread of nursing care had been raised, require an assessment of the presence of, and volume of strain sores. In a German look at, Tsokos et al. examined 10,222 bodies prior to cremation for strain sores, and observed that there has been a fantastic correlation among their incidence and increasing age (specifically in women over 80 years). They have been additionally more generally located in those who had senile dementia, neurological diseases and terrible vitamins (especially marasmus). Citizens of nursing homes/senior citizen's houses have been most possibly to have strain sores than those residing at domestic. Superior grade sores (with deeper tissues being concerned) were found in 87%, with 69% being located over the sacrum. In those with more than one sores, they have been located inside the following mixtures; greater trochanter and sacrum-4%, hip and sacrum 3.2%, thoracic spinal column and sacrum 2.4%.
Wound healing is a complex organic manner that includes hemostasis, inflammation, proliferation, and remodeling. Massive numbers of cellular kinds, consisting of neutrophils, macrophages, lymphocytes, keratinocytes, fibroblasts, and endothelial cells, are worried in this process. More than one element can motive impaired wound restoration by way of affecting one or extra phases of the manner and are labeled into nearby and systemic elements. The impacts of these elements are not at the same time distinctive. Single or multiple factors may additionally play a role in anyone or extraindividual phases, contributing to the general final results of the healing system.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
|1||Nguyen DT, Orgill DP, Murphy GT. The Pathophysiologic Basis for Wound Healing and Cutaneous Regeneration. Biomaterials for Treating Skin Loss. Berlin, Germany: Elsevier; 2009. p. 25-57.|
|2||Zhong SP, Zhang YZ, Lim CT. Tissue scaffolds for skin wound healing and dermal reconstruction. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2010;2:510-25.|
|3||Shaw TJ, Martin P. Wound repair at a glance. J Cell Sci 2009;122:3209-13.|
|4||Eming SA, Krieg T, Davidson JM. Inflammation in wound repair: Molecular and cellular mechanisms. J Invest Dermatol 2007;127:514-25.|
|5||Metcalfe AD, Ferguson MW. Skin stem and progenitor cells: Using regeneration as a tissue-engineering strategy. Cell Mol Life Sci 2008;65:24-32.|
|6||Trent JT, Kirsner RS. Wounds and malignancy. Adv Skin Wound Care 2003;16:31-4.|
|7||Troxler M, Vowden K, Vowden P. Integrating Adjunctive Therapy Into Practice: The Importance of Recognising 'Hard-To-Heal' Wounds. World Wide Wounds; 2006.|
|8||Maxson S, Lopez EA, Yoo D, Danilkovitch-Miagkova A, Leroux MA. Concise review: Role of mesenchymal stem cells in wound repair. Stem Cells Transl Med 2012;1:142-9.|
|9||Glat PM, Longaker MT. Wound healing. In: Aston SJ, Beasley RW, Thorne CH, editors. Grabb and Smith's Plastic Surgery, 5th ed. Philadelphia: Lippincott–Raven; 1997. p. 3-12.|
|10||Hawkins DH, Abrahamse H. The role of laser fluence in cell viability, proliferation, and membrane integrity of wounded human skin fibroblasts following helium-neon laser irradiation. Lasers Surg Med 2006;38:74-83.|
|11||Zimber MP, Mansbridge JN, Taylor M, Stockton T, Hubka M, Baumgartner M, et al. Human cell-conditioned media produced under embryonic-like conditions result in improved healing time after laser resurfacing. Aesthetic Plast Surg 2012;36:431-7.|
|12||Mackool RJ, Gittes GK, Longaker MT. Scarless healing. The fetal wound. Clin Plast Surg 1998;25:357-65.|
|13||Ferguson MW, O'Kane S. Scar-free healing: From embryonic mechanisms to adult therapeutic intervention. Philos Trans R Soc Lond B Biol Sci 2004;359:839-50.|
|14||Penn JW, Grobbelaar AO, Rolfe KJ. The role of the TGF-β family in wound healing, burns and scarring: A review. Int J Burns Trauma 2012;2:18-28.|
|15||Thom SR. Hyperbaric oxygen: Its mechanisms and efficacy. Plast Reconstr Surg 2011;127 Suppl 1:131S-41S.|
|16||Martin P. Wound healing--aiming for perfect skin regeneration. Science 1997;276:75-81.|
|17||Medrado AR, Pugliese LS, Reis SR, Andrade ZA. Influence of low level laser therapy on wound healing and its biological action upon myofibroblasts. Lasers Surg Med 2003;32:239-44.|
|18||Buckley CD. Why does chronic inflammation persist: An unexpected role for fibroblasts. Immunol Lett 2011;138:12-4.|
|19||Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature 2008;453:314-21.|
|20||Nunes PS, Albuquerque RL Jr, Cavalcante DR, Dantas MD, Cardoso JC, Bezerra MS, et al. Collagen-based films containing liposome-loaded usnic acid as dressing for dermal burn healing. J Biomed Biotechnol 2011;2011:761593.|
|21||Thuraisingam T, Xu YZ, Eadie K, Heravi M, Guiot MC, Greemberg R, et al. MAPKAPK-2 signaling is critical for cutaneous wound healing. J Invest Dermatol 2010;130:278-86.|
|22||Rodero MP, Khosrotehrani K. Skin wound healing modulation by macrophages. Int J Clin Exp Pathol 2010;3:643-53.|
|23||Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med 1999;341:738-46.|
|24||Tidball JG. Inflammatory processes in muscle injury and repair. Am J Physiol Regul Integr Comp Physiol 2005;288:R345-53.|
|25||Li J, Chen J, Kirsner R. Pathophysiology of acute wound healing. Clin Dermatol 2007;25:9-18.|
|26||Mendonça RJ, Coutinho-Netto J. Cellular aspects of wound healing. An Bras Dermatol 2009;84:257-62.|
|27||Günter CI, Machens HG. New strategies in clinical care of skin wound healing. Eur Surg Res 2012;49:16-23.|
|28||Burnouf T, Goubran HA, Chen TM, Ou KL, El-Ekiaby M, Radosevic M. Blood-derived biomaterials and platelet growth factors in regenerative medicine. Blood Rev 2013;27:77-89.|
|29||Giusti I, Rughetti A, D'Ascenzo S, Di Stefano G, Nanni MR, Millimaggi D, et al. The effects of platelet gel-released supernatant on human fibroblasts. Wound Repair Regen 2013;21:300-8.|
|30||Posthauer ME, Collins N, Dorner B, Sloan C. Nutritional strategies for frail older adults. Adv Skin Wound Care 2013;26:128-40.|
|31||Posthauer ME. The role of nutrition in wound care. Adv Skin Wound Care 2012;25:62-3.|
|32||Boyapati L, Wang HL. The role of stress in periodontal disease and wound healing. Periodontol 2000 2007;44:195-210.|
|33||Brem H, Tomic-Canic M. Cellular and molecular basis of wound healing in diabetes. J Clin Invest 2007;117:1219-22.|
|34||Broughton G 2nd, Janis JE, Attinger CE. The basic science of wound healing. Plast Reconstr Surg 2006;117:12S-34S.|
|35||Burgess C. Topical vitamins. J Drugs Dermatol 2008;7:s2-6.|
|36||Calabro P, Yeh ET. Obesity, inflammation, and vascular disease: The role of the adipose tissue as an endocrine organ. Subcell Biochem 2007;42:63-91.|
|37||Campos AC, Groth AK, Branco AB. Assessment and nutritional aspects of wound healing. Curr Opin Clin Nutr Metab Care 2008;11:281-8.|
|38||Cha J, Falanga V. Stem cells in cutaneous wound healing. Clin Dermatol. 2007;25:73-78.|
|39||Chan LK, Withey S, Butler PE. Smoking and wound healing problems in reduction mammaplasty: Is the introduction of urine nicotine testing justified? Ann Plast Surg 2006;56:111-5.|
|40||Choudhry MA, Chaudry IH. Alcohol intoxication and post-burn complications. Front Biosci 2006;11:998-1005.|
|41||da Costa MA, Campos AC, Coelho JC, de Barros AM, Matsumoto HM. Oral glutamine and the healing of colonic anastomoses in rats. JPEN J Parenter Enteral Nutr 2003;27:182-5.|
|42||Davis SC, Ricotti C, Cazzaniga A, Welsh E, Eaglstein WH, Mertz PM. Microscopic and physiologic evidence for biofilm-associated wound colonization in vivo. Wound Repair Regen 2008;16:23-9.|
|43||de Mello VD, Kolehmainen M, Schwab U, Mager U, Laaksonen DE, Pulkkinen L, et al. Effect of weight loss on cytokine messenger RNA expression in peripheral blood mononuclear cells of obese subjects with the metabolic syndrome. Metabolism 2008;57:192-9.|
|44||Dong YL, Fleming RY, Yan TZ, Herndon DN, Waymack JP. Effect of ibuprofen on the inflammatory response to surgical wounds. J Trauma 1993;35:340-3.|
|45||Dvivedi S, Tiwari SM, Sharma A. Effect of ibuprofen and diclofenac sodium on experimental would healing. Indian J Exp Biol 1997;35:1243-5.|
|46||Edwards R, Harding KG. Bacteria and wound healing. Curr Opin Infect Dis 2004;17:91-6.|
|47||Emery CF, Kiecolt-Glaser JK, Glaser R, Malarkey WB, Frid DJ. Exercise accelerates wound healing among healthy older adults: A preliminary investigation. J Gerontol A Biol Sci Med Sci 2005;60:1432-6.|
|48||Fitzgerald DJ, Radek KA, Chaar M, Faunce DE, DiPietro LA, Kovacs EJ. Effects of acute ethanol exposure on the early inflammatory response after excisional injury. Alcohol Clin Exp Res 2007;31:317-23.|
|49||Fontana L, Eagon JC, Colonna M, Klein S. Impaired mononuclear cell immune function in extreme obesity is corrected by weight loss. Rejuvenation Res 2007;10:41-6.|
|50||Franz MG, Steed DL, Robson MC. Optimizing healing of the acute wound by minimizing complications. Curr Probl Surg 2007;44:691-763.|
|51||Galiano RD, Tepper OM, Pelo CR, Bhatt KA, Callaghan M, Bastidas N, et al. Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. Am J Pathol 2004;164:1935-47.|
|52||Galkowska H, Olszewski WL, Wojewodzka U, Rosinski G, Karnafel W. Neurogenic factors in the impaired healing of diabetic foot ulcers. J Surg Res 2006;134:252-8.|
|53||Gallagher KA, Liu ZJ, Xiao M, Chen H, Goldstein LJ, Buerk DG, et al. Diabetic impairments in NO-mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF-1 alpha. J Clin Invest 2007;117:1249-59.|
|54||Gawronska-Kozak B, Bogacki M, Rim JS, Monroe WT, Manuel JA. Scarless skin repair in immunodeficient mice. Wound Repair Regen 2006;14:265-76.|
|55||Gentilello LM, Cobean RA, Walker AP, Moore EE, Wertz MJ, Dellinger EP. Acute ethanol intoxication increases the risk of infection following penetrating abdominal trauma. J Trauma 1993;34:669-74.|
|56||Gilliver SC, Ashworth JJ, Ashcroft GS. The hormonal regulation of cutaneous wound healing. Clin Dermatol 2007;25:56-62.|
|57||Hofman D, Moore K, Cooper R, Eagle M, Cooper S. Use of topical corticosteroids on chronic leg ulcers. J Wound Care 2007;16:227-30.|
|58||Huijberts MS, Schaper NC, Schalkwijk CG. Advanced glycation end products and diabetic foot disease. Diabetes Metab Res Rev 2008;24 Suppl 1:S19-24.|
|59||Jacobi J, Jang JJ, Sundram U, Dayoub H, Fajardo LF, Cooke JP. Nicotine accelerates angiogenesis and wound healing in genetically diabetic mice. Am J Pathol 2002;161:97-104.|
|60||Jameson J, Havran WL. Skin gammadelta T-cell functions in homeostasis and wound healing. Immunol Rev 2007;215:114-22.|
|61||Jensen JA, Goodson WH, Hopf HW, Hunt TK. Cigarette smoking decreases tissue oxygen. Arch Surg 1991;126:1131-4.|
|62||Moschidou D, Mukherjee S, Blundell MP, Drews K, Jones GN, Abdulrazzak H, et al. Valproic acid confers functional pluripotency to human amniotic fluid stem cells in a transgene-free approach. Mol Ther 2012;20:1953-67.|
|63||Moschidou D, Mukherjee S, Blundell MP, Jones GN, Atala AJ, Thrasher AJ, et al. Human mid-trimester amniotic fluid stem cells cultured under embryonic stem cell conditions with valproic acid acquire pluripotent characteristics. Stem Cells Dev 2013;22:444-58.|
|64||Kumar V, Abbas AK, Aster JC, Robbins SL. Robbins basic pathology. Philadelphia, PA: Elsevier/Saunders; 2013.|
|65||Sood A, Granick MS, Tomaselli NL. Wound Dressings and Comparative Effectiveness Data. Adv Wound Care (New Rochelle) 2014;3:511-29.|
|66||Pham C, Greenwood J, Cleland H, Woodruff P, Maddern G. Bioengineered skin substitutes for the management of burns: A systematic review. Burns 2007;33:946-57.|
|67||Mogoşanu GD, Grumezescu AM. Natural and synthetic polymers for wounds and burns dressing. Int J Pharm 2014;463:127-36.|
|68||Kamolz LP, Wild T. Wound bed preparation: The impact of debridement and wound cleansing. Wound Med 2013;1:44-50.|
|69||Lee CH, Singla A, Lee Y. Biomedical applications of collagen. Int J Pharm 2001;221:1-22.|
|70||Moura LI, Dias AM, Carvalho E, de Sousa HC. Recent advances on the development of wound dressings for diabetic foot ulcer treatment–A review. Acta Biomater 2013;9:7093-114.|
|71||Gopinath D, Ahmed MR, Gomathi K, Chitra K, Sehgal PK, Jayakumar R. Dermal wound healing processes with curcumin incorporated collagen films. Biomaterials 2004;25:1911-7.|
|72||Russell RCG, NS Williams, CJK Bulstrode, editors. Bailey and Love's short practice of surgery. 282 × 222 mm. Illustrated. 2000. 23rd ed. London: Arnold. W. H. Allum. Epsom General... First published; 2002. p. 1348.|
|73||Tsokos M, Heinemann A, Püschel K. Pressure sores: Epidemiology, medico-legal implications and forensic argumentation concerning causality. Int J Legal Med 2000;113:283-7.|