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Wound healing
This article may be too technical for most readers to understand. (March 2014) |
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Wound healing is an intricate process whereby the skin (or another organ-tissue) repairs itself after injury.[1] In normal skin, the epidermis (outermost layer) and dermis (inner or deeper layer) exist in a steady-state equilibrium and shield from the external environment. When the skin is broken, the normal (physiologic) process of wound healing begins. The classic model of wound healing comprises three or four sequential, yet overlapping,[2] phases: (1) hemostasis (not considered a phase by some authors), (2) inflammation, (3) proliferation and (4) remodeling.[3] Upon injury to the skin, a set of complex biochemical events takes place in a closely orchestrated cascade to repair the damage.[2]
Within the first few minutes after the injury, platelets (thrombocytes) aggregate (join together) at the injury site to form a fibrin clot, which reduces active bleeding (hemostasis). The speed of wound healing depends on bloodstream levels of platelets, fibrin, and hormones such as oxytocin.[4]
During the inflammation phase, bacteria and cell debris are phagocytosed and removed from the wound by white blood cells. Blood factors are released into the wound that cause the migration and division of cells during the proliferative phase.
The proliferation phase is characterized by angiogenesis, collagen deposition, granulation tissue formation, epithelialization, and wound contraction.[5] In angiogenesis, vascular endothelial cells form new blood vessels.[6] In fibroplasia and granulation tissue formation, fibroblasts grow and form a new, provisional extracellular matrix (ECM) by excreting collagen and fibronectin.[5] Concurrently, re-epithelialization of the epidermis occurs, whereby epithelial cells proliferate and 'crawl' atop the wound bed, covering the new tissue.[7]
During wound contraction, myofibroblasts decrease the size of the wound by gripping the wound edges and contracting using a mechanism that resembles that of smooth muscle cells. When the cells' roles are close to complete, unneeded cells undergo apoptosis.[5]
During maturation and remodeling, collagen is remodeled and realigned along tension lines, and apoptosis removes unnecessary cells.
This process is fragile and susceptible to interruption or failure that can cause the formation of non-healing chronic wounds. Among the factors that may contribute are diabetes, venous or arterial disease, infection, and metabolic deficiencies of old age.[8]
- 1 Early vs cellular phase
- 2 Inflammatory phase
- 3 Proliferative phase
- 4 Maturation and remodeling
- 5 Factors affecting wound healing
- 6 Research and development
- 7 Simulating wound healing from a growth perspective
- 8 Types
- 9 Overview of involved growth factors
- 10 See also
- 11 Notes and references
- 12 External links
Early vs cellular phase[edit]
Wound healing classically comprises hemostasis, inflammation, proliferation, and remodeling. Although a useful construct, this model employs considerable overlapping among individual phases: a complementary model has recently been described[1] wherein the many elements of wound healing are more clearly defined. The importance of this new model becomes more apparent through its utility in the fields of regenerative medicine and tissue engineering (see Research and development section below). In this construct, the process of wound healing comprises two major phases: the early phase and the cellular phase:[1]
The early phase, which begins immediately after skin injury, involves cascading molecular and cellular events that cause hemostasis and formation of an early, makeshift extracellular matrix that provides structural support for cellular attachment and subsequent cellular proliferation.
The cellular phase involves several types of cells' cooperatively mounting an inflammatory response, synthesizing granulation tissue, and restoring the epithelial layer.[1] Subdivisions of the cellular phase are: [1] Macrophages and inflammatory components (within 1–2 days), [2] Epithelial-mesenchymal interaction: re-epithelialization (phenotype change within hours, migration begins on day 1 or 2), [3] Fibroblasts and myofibroblasts: progressive alignment, collagen production, and matrix contraction (between day 4 day 14), [4] Endothelial cells and angiogenesis (begins on day 4), [5] Dermal matrix: elements of fabrication (begins on day 4, lasting 2 weeks) and alteration/remodeling (begins after week 2, lasting weeks to months—depending on wound size).[1]
Inflammatory phase[edit]
Just before the inflammatory phase, the clotting cascade occurs in order to achieve hemostasis, or stop blood loss by way of a fibrin clot. Various soluble factors (including chemokines and cytokines) thereafter are released to attract cells that phagocytise debris, bacteria, and damaged tissue and release signaling molecules that initiate the proliferative phase of wound healing.
Clotting cascade[edit]
When tissue is first wounded, blood touches collagen, causing blood platelets to secrete inflammatory factors.[11] Platelets also express sticky glycoproteins on their cell membranes that allow them to aggregate.[5]
Fibrin and fibronectin link together and form a plug that traps proteins and particles and prevents further blood loss.[12] This fibrin-fibronectin plug is also the main structural support for the wound until collagen is deposited.[5] Migratory cells use this plug as a matrix across which to crawl, and platelets adhere to it and secrete factors.[5] The clot is eventually lysed and replaced with granulation tissue and then later with collagen.
Platelets, the most numerous cells soon after wounding, into the blood release such substances as ECM proteins and cytokines, including growth factors.[11] Growth factors stimulate cells to speed their rate of division. Platelets also release other proinflammatory factors like serotonin, bradykinin, prostaglandins, prostacyclins, thromboxane, and histamine,[2] which serve such purposes as increasing cell proliferation and migration to the area and causing blood vessels to become dilated and porous.
Vasoconstriction and vasodilation[edit]
Immediately after a blood vessel is breached, ruptured cell membranes release such inflammatory factors as thromboxanes and prostaglandins that cause the vessel to spasm to prevent blood loss and collect inflammatory cells and factors in the area.[2] This vasoconstriction lasts five to ten minutes and is followed by vasodilation, a widening of blood vessels, which peaks at about 20 minutes post-wounding.[2] Vasodilation is the result of factors that platelets and other cells release. The main factor involved in causing vasodilation is histamine.[2][11] Histamine also causes blood vessels to become porous, allowing the tissue to become edematous because proteins from the bloodstream leak into the extravascular space, which increases its osmolar load and draws water into the area.[2] Increased porosity of blood vessels also facilitates the entry of inflammatory cells like leukocytes into the wound site from the bloodstream.[13][14]
Polymorphonuclear neutrophils[edit]
Within an hour of wounding, polymorphonuclear neutrophils (PMNs) arrive at the wound site and become the predominant cells in the wound for the first two days after the injury occurs, with especially high numbers on the second day.[15] Fibronectin, growth factors, and such substances as kinins attract them to the wound. Neutrophils phagocytise debris and bacteria, kill bacteria by releasing free radicals in what is called a 'respiratory burst,'[16][17] and cleanse the wound by secreting proteases that decompose damaged tissue. Neutrophils usually undergo apoptosis after completing their tasks and are engulfed and degraded by macrophages.[18]
Other leukocytes to enter the area include helper T cells, which secrete cytokines to cause more T cells to divide and to increase inflammation and enhance vasodilation and vessel permeability.[13][19] T cells also increase the activity of macrophages.[13]
One of the macrophage's roles is to phagocytize other expended phagocytes,[20] bacteria and damaged tissue,[15] and they also debride damaged tissue by releasing proteases.[21]
Macrophages function in regeneration[22][23] and are essential for wound healing.[15] They are stimulated by the low oxygen content of their surroundings to produce factors that induce and speed angiogenesis[16] and they also stimulate cells that reepithelialize the wound, create granulation tissue, and lay down a new extracellular matrix.[24][25] By secreting these factors, macrophages contribute to pushing the wound healing process into the next phase. They replace PMNs as the predominant cells in the wound by two days after injury.[20]
The spleen contains half the body's monocytes in reserve ready to be deployed to injured tissue.[26][27] Attracted to the wound site by growth factors released by platelets and other cells, monocytes from the bloodstream enter the area through blood vessel walls.[28] Numbers of monocytes in the wound peak one to one and a half days after the injury occurs.[19] Once they are in the wound site, monocytes mature into macrophages. Macrophages also secrete a number of factors such as growth factors and other cytokines, especially during the third and fourth post-wounding days. These factors attract cells involved in the proliferation stage of healing to the area.[11]
In wound healing that result in incomplete repair, scar contraction occurs, bringing varying gradations of structural imperfections, deformities and problems with flexibility.[29] Macrophages may restrain the contraction phase.[23] Scientists have reported that removing the macrophages from a salamander resulted in failure of a typical regeneration response (limb regeneration), instead bringing on a repair (scarring) response.[30][31]
Decline of inflammatory phase[edit]
As inflammation dies down, fewer inflammatory factors are secreted, existing ones are broken down, and numbers of neutrophils and macrophages are reduced at the wound site.[15] These changes indicate that the inflammatory phase is ending and the proliferative phase is underway.[15] In vitro evidence, obtained using the dermal equivalent model, suggests that the presence of macrophages actually delays wound contraction and thus the disappearance of macrophages from the wound may be essential for subsequent phases to occur.[23]
Because inflammation plays roles in fighting infection, clearing debris and inducing the proliferation phase, it is a necessary part of healing. However, inflammation can lead to tissue damage if it lasts too long.[5] Thus the reduction of inflammation is frequently a goal in therapeutic settings. Inflammation lasts as long as there is debris in the wound. Thus, if the individual's immune system is compromised and is unable to clear the debris from the wound and/or if excessive detritus, devitalized tissue, or microbial biofilm is present in the wound, these factors may cause a prolonged inflammatory phase and prevent the wound from properly commencing the proliferation phase of healing. This can lead to a chronic wound.
Proliferative phase[edit]
About two or three days after the wound occurs, fibroblasts begin to enter the wound site, marking the onset of the proliferative phase even before the inflammatory phase has ended.[32] As in the other phases of wound healing, steps in the proliferative phase do not occur in a series but rather partially overlap in time.
Also called neovascularization, the process of angiogenesis occurs concurrently with fibroblast proliferation when endothelial cells migrate to the area of the wound.[33] Because the activity of fibroblasts and epithelial cells requires oxygen and nutrients, angiogenesis is imperative for other stages in wound healing, like epidermal and fibroblast migration. The tissue in which angiogenesis has occurred typically looks red (is erythematous) due to the presence of capillaries.[33]
Stem cells of endothelial cells, originating from parts of uninjured blood vessels, develop pseudopodia and push through the ECM into the wound site to establish new blood vessels.[16]
Endothelial cells are attracted to the wound area by fibronectin found on the fibrin scab and chemotactically by angiogenic factors released by other cells,[34] e.g. from macrophages and platelets when in a low-oxygen environment. Endothelial growth and proliferation is also directly stimulated by hypoxia, and presence of lactic acid in the wound.[32]
To migrate, endothelial cells need collagenases and plasminogen activator to degrade the clot and part of the ECM.[2][15] Zinc-dependent metalloproteinases digest basement membrane and ECM to allow cell migration, proliferation and angiogenesis.[35]
When macrophages and other growth factor-producing cells are no longer in a hypoxic, lactic acid-filled environment, they stop producing angiogenic factors.[16] Thus, when tissue is adequately perfused, migration and proliferation of endothelial cells is reduced. Eventually blood vessels that are no longer needed die by apoptosis.[34]
Fibroplasia and granulation tissue formation[edit]
Simultaneously with angiogenesis, fibroblasts begin accumulating in the wound site. Fibroblasts begin entering the wound site two to five days after wounding as the inflammatory phase is ending, and their numbers peak at one to two weeks post-wounding.[15] By the end of the first week, fibroblasts are the main cells in the wound.[2] Fibroplasia ends two to four weeks after wounding.
In the first two or three days after injury, fibroblasts mainly migrate and proliferate, while later, they are the main cells that lay down the collagen matrix in the wound site.[2] Origins of these fibroblasts are thought to be from the adjacent uninjured cutaneous tissue (although new evidence suggests that some are derived from blood-borne, circulating adult stem cells/precursors).[36] Initially fibroblasts utilize the fibrin cross-linking fibers (well-formed by the end of the inflammatory phase) to migrate across the wound, subsequently adhering to fibronectin.[34] Fibroblasts then deposit ground substance into the wound bed, and later collagen, which they can adhere to for migration.[11]
Granulation tissue functions as rudimentary tissue, and begins to appear in the wound already during the inflammatory phase, two to five days post wounding, and continues growing until the wound bed is covered. Granulation tissue consists of new blood vessels, fibroblasts, inflammatory cells, endothelial cells, myofibroblasts, and the components of a new, provisional extracellular matrix (ECM). The provisional ECM is different in composition from the ECM in normal tissue and its components originate from fibroblasts.[24] Such components include fibronectin, collagen, glycosaminoglycans, elastin, glycoproteins and proteoglycans.[34] Its main components are fibronectin and hyaluronan, which create a very hydrated matrix and facilitate cell migration.[28] Later this provisional matrix is replaced with an ECM that more closely resembles that found in non-injured tissue.
Growth factors (PDGF, TGF-β) and fibronectin encourage proliferation, migration to the wound bed, and production of ECM molecules by fibroblasts. Fibroblasts also secrete growth factors that attract epithelial cells to the wound site. Hypoxia also contributes to fibroblast proliferation and excretion of growth factors, though too little oxygen will inhibit their growth and deposition of ECM components, and can lead to excessive, fibrotic scarring.
Collagen deposition[edit]
One of fibroblasts' most important duties is the production of collagen.[33]
Collagen deposition is important because it increases the strength of the wound; before it is laid down, the only thing holding the wound closed is the fibrin-fibronectin clot, which does not provide much resistance to traumatic injury.[16] Also, cells involved in inflammation, angiogenesis, and connective tissue construction attach to, grow and differentiate on the collagen matrix laid down by fibroblasts.[37]
Type III collagen and fibronectin are generally beginning to be produced in appreciable amounts at somewhere between approximately 10 hours[38] and 3 days,[34] depending mainly on wound size. Their deposition peaks at one to three weeks.[24] They are the predominating tensile substances until the later phase of maturation, in which they are replaced by the stronger type I collagen.
Even as fibroblasts are producing new collagen, collagenases and other factors degrade it. Shortly after wounding, synthesis exceeds degradation so collagen levels in the wound rise, but later production and degradation become equal so there is no net collagen gain.[16] This homeostasis signals the onset of the later maturation phase. Granulation gradually ceases and fibroblasts decrease in number in the wound once their work is done.[39] At the end of the granulation phase, fibroblasts begin to commit apoptosis, converting granulation tissue from an environment rich in cells to one that consists mainly of collagen.[2]
The formation of granulation tissue into an open wound allows the reepithelialization phase to take place, as epithelial cells migrate across the new tissue to form a barrier between the wound and the environment.[34] Basal keratinocytes from the wound edges and dermal appendages such as hair follicles, sweat glands and sebacious (oil) glands are the main cells responsible for the epithelialization phase of wound healing.[39] They advance in a sheet across the wound site and proliferate at its edges, ceasing movement when they meet in the middle. Though in healing that results in a scar, sweat glands and hair follicles do not form.[40]
Keratinocytes migrate without first proliferating.[41] Migration can begin as early as a few hours after wounding. However, epithelial cells require viable tissue to migrate across, so if the wound is deep it must first be filled with granulation tissue.[42] Thus the time of onset of migration is variable and may occur about one day after wounding.[43] Cells on the wound margins proliferate on the second and third day post-wounding in order to provide more cells for migration.[24]
If the basement membrane is not breached, epithelial cells are replaced within three days by division and upward migration of cells in the stratum basale in the same fashion that occurs in uninjured skin.[34] However, if the basement membrane is ruined at the wound site, reepithelization must occur from the wound margins and from skin appendages such as hair follicles and sweat and oil glands that enter the dermis that are lined with viable keratinocytes.[24] If the wound is very deep, skin appendages may also be ruined and migration can only occur from wound edges.[42]
Migration of keratinocytes over the wound site is stimulated by lack of contact inhibition and by chemicals such as nitric oxide.[44] Before they begin to migrate, cells must dissolve their desmosomes and hemidesmosomes, which normally anchor the cells by intermediate filaments in their cytoskeleton to other cells and to the ECM.[19] Transmembrane receptor proteins called integrins, which are made of glycoproteins and normally anchor the cell to the basement membrane by its cytoskeleton, are released from the cell's intermediate filaments and relocate to actin filaments to serve as attachments to the ECM for pseudopodia during migration.[19] Thus keratinocytes detach from the basement membrane and are able to enter the wound bed.[32]
Before they begin migrating, keratinocytes change shape, becoming longer and flatter and extending cellular processes like lamellipodia and wide processes that look like ruffles.[28] Actin filaments and pseudopodia form.[32] During migration, integrins on the pseudopod attach to the ECM, and the actin filaments in the projection pull the cell along.[19] The interaction with molecules in the ECM through integrins further promotes the formation of actin filaments, lamellipodia, and filopodia.[19]
Epithelial cells climb over one another in order to migrate.[39] This growing sheet of epithelial cells is often called the epithelial tongue.[41] The first cells to attach to the basement membrane form the stratum basale. These basal cells continue to migrate across the wound bed, and epithelial cells above them slide along as well.[41] The more quickly this migration occurs, the less of a scar there will be.[45]
Fibrin, collagen, and fibronectin in the ECM may further signal cells to divide and migrate. Like fibroblasts, migrating keratinocytes use the fibronectin cross-linked with fibrin that was deposited in inflammation as an attachment site to crawl across.[21][28][39]
As keratinocytes migrate, they move over granulation tissue but underneath the scab (if one was formed), separating it from the underlying tissue.[39][43] Epithelial cells have the ability to phagocytize debris such as dead tissue and bacterial matter that would otherwise obstruct their path. Because they must dissolve any scab that forms, keratinocyte migration is best enhanced by a moist environment, since a dry one leads to formation of a bigger, tougher scab.[21][34][39][46] To make their way along the tissue, keratinocytes must dissolve the clot, debris, and parts of the ECM in order to get through.[43][47] They secrete plasminogen activator, which activates plasminogen, turning it into plasmin to dissolve the scab. Cells can only migrate over living tissue,[39] so they must excrete collagenases and proteases like matrix metalloproteinases (MMPs) to dissolve damaged parts of the ECM in their way, particularly at the front of the migrating sheet.[43] Keratinocytes also dissolve the basement membrane, using instead the new ECM laid down by fibroblasts to crawl across.[19]
As keratinocytes continue migrating, new epithelial cells must be formed at the wound edges to replace them and to provide more cells for the advancing sheet.[21] Proliferation behind migrating keratinocytes normally begins a few days after wounding[42] and occurs at a rate that is 17 times higher in this stage of epithelialization than in normal tissues.[21] Until the entire wound area is resurfaced, the only epithelial cells to proliferate are at the wound edges.[41]
Growth factors, stimulated by integrins and MMPs, cause cells to proliferate at the wound edges. Keratinocytes themselves also produce and secrete factors, including growth factors and basement membrane proteins, which aid both in epithelialization and in other phases of healing.[48] Growth factors are also important for the innate immune defense of skin wounds by stimulation of the production of antimicrobial peptides and neutrophil chemotactic cytokines in keratinocytes.
Keratinocytes continue migrating across the wound bed until cells from either side meet in the middle, at which point contact inhibition causes them to stop migrating.[28] When they have finished migrating, the keratinocytes secrete the proteins that form the new basement membrane.[28] Cells reverse the morphological changes they underwent in order to begin migrating; they reestablish desmosomes and hemidesmosomes and become anchored once again to the basement membrane.[19] Basal cells begin to divide and differentiate in the same manner as they do in normal skin to reestablish the strata found in reepithelialized skin.[28]
Contraction is a key phase of wound healing with repair. If contraction continues for too long, it can lead to disfigurement and loss of function.[29] Thus there is a great interest in understanding the biology of wound contraction, which can be modelled in vitro using the collagen gel contraction assay or the dermal equivalent model.[23][49]
Contraction commences approximately a week after wounding, when fibroblasts have differentiated into myofibroblasts [50] In full thickness wounds, contraction peaks at 5 to 15 days post wounding.[34] Contraction can last for several weeks[42] and continues even after the wound is completely reepithelialized.[2] A large wound can become 40 to 80% smaller after contraction.[28][39] Wounds can contract at a speed of up to 0.75 mm per day, depending on how loose the tissue in the wounded area is.[34] Contraction usually does not occur symmetrically; rather most wounds have an 'axis of contraction' which allows for greater organization and alignment of cells with collagen.[50]
At first, contraction occurs without myofibroblast involvement.[51] Later, fibroblasts, stimulated by growth factors, differentiate into myofibroblasts. Myofibroblasts, which are similar to smooth muscle cells, are responsible for contraction.[51] Myofibroblasts contain the same kind of actin as that found in smooth muscle cells.[29]
Myofibroblasts are attracted by fibronectin and growth factors and they move along fibronectin linked to fibrin in the provisional ECM in order to reach the wound edges.[21] They form connections to the ECM at the wound edges, and they attach to each other and to the wound edges by desmosomes. Also, at an adhesion called the fibronexus, actin in the myofibroblast is linked across the cell membrane to molecules in the extracellular matrix like fibronectin and collagen.[51] Myofibroblasts have many such adhesions, which allow them to pull the ECM when they contract, reducing the wound size.[29] In this part of contraction, closure occurs more quickly than in the first, myofibroblast-independent part.[51]
As the actin in myofibroblasts contracts, the wound edges are pulled together. Fibroblasts lay down collagen to reinforce the wound as myofibroblasts contract.[2] The contraction stage in proliferation ends as myofibroblasts stop contracting and commit apoptosis.[29] The breakdown of the provisional matrix leads to a decrease in hyaluronic acid and an increase in chondroitin sulfate, which gradually triggers fibroblasts to stop migrating and proliferating.[15] These events signal the onset of the maturation stage of wound healing.
Maturation and remodeling[edit]
When the levels of collagen production and degradation equalize, the maturation phase of tissue repair is said to have begun.[16] During maturation, type III collagen, which is prevalent during proliferation, is replaced by type I collagen.[13] Originally disorganized collagen fibers are rearranged, cross-linked, and aligned along tension lines.[28] The onset of the maturation phase may vary extensively, depending on the size of the wound and whether it was initially closed or left open,[24] ranging from approximately 3 days[38] to 3 weeks.[52] The maturation phase can last for a year or longer, similarly depending on wound type.[24]
As the phase progresses, the tensile strength of the wound increases, with the strength approaching 50% that of normal tissue by three months after injury and ultimately becoming as much as 80% as strong as normal tissue.[24] Since activity at the wound site is reduced, the scar loses its red appearance as blood vessels that are no longer needed are removed by apoptosis.[16]
The phases of wound healing normally progress in a predictable, timely manner; if they do not, healing may progress inappropriately to either a chronic wound [5] such as a venous ulcer or pathological scarring such as a keloid scar.[53][54]
Factors affecting wound healing[edit]
This section does not cite any references or sources. (January 2014) |
Many factors controlling the efficacy, speed, and manner of wound healing fall under two types: local and systemic Factors.
Local factors[edit]
- Mechanical factors
- Edema
- Ischemia and necrosis
- Foreign bodies
- Low oxygen tension
Systemic factors[edit]
- Inadequate perfusion
- Inflammation
- Diabetes
- Nutrients
- Metabolic diseases
- Immunosuppression
- Connective tissue disorders
- Smoking
Research and development[edit]
Up until a decade ago, the classic paradigm of wound healing, involving stem cells restricted to organ-specific lineages, had never been seriously challenged. Since then, the notion of adult stem cells having cellular plasticity or the ability to differentiate into non-lineage cells has emerged as an alternative explanation.[1] To be more specific, hematopoietic progenitor cells (that give rise to mature cells in the blood) may have the ability de-differentiate back into hematopoietic stem cells and/or transdifferentiate into non-lineage cells, such as fibroblasts.[36]
Stem cells and cellular plasticity[edit]
Multipotent adult stem cells have the capacity to be self-renewing and give rise to different cell types. Stem cells give rise to progenitor cells, which are cells that are not self-renewing, but can generate several types of cells. The extent of stem cell involvement in cutaneous (skin) wound healing is complex and not fully understood.
It is thought that the epidermis and dermis are reconstituted by mitotically active stem cells that reside at the apex of rete ridges (basal stem cells or BSC), the bulge of hair follicles (hair follicular stem cell or HFSC), and the papillary dermis (dermal stem cells).[1] Moreover, bone marrow may also contain stem cells that play a major role in cutaneous wound healing.[36]
In rare circumstances, such as extensive cutaneous injury, self-renewal subpopulations in the bone marrow are induced to participate in the healing process, whereby they give rise to collagen-secreting cells that seem to play a role during wound repair.[1] These two self-renewal subpopulations are (1) bone marrow-derived mesenchymal stem cells (MSC) and (2) hematopoietic stem cells (HSC). Bone marrow also harbors a progenitor subpopulation (endothelial progenitor cells or EPC) that, in the same type of setting, are mobilized to aid in the reconstruction of blood vessels.[36] Moreover, it thought that, extensive injury to skin also promotes the early trafficking of a unique subclass of leukocytes (circulating fibrocytes) to the injured region, where they perform various functions related to wound healing.[1]
Wound repair versus regeneration[edit]
An injury is an interruption of morphology and/or functionality of a given tissue. After injury, structural tissue heals with incomplete or complete regeneration.[55][56] On the other hand, tissue without an interruption to morphology almost always completely regenerates. An example of complete regeneration without an interruption of the morphology is non-injured tissue, such as skin.[57] Non-injured skin has a continued replacement and regeneration of cells which always results in complete regeneration.[57]
There is a subtle distinction between 'repair' and 'regeneration'.[1][55][56] Repair means incomplete regeneration.[55] Repair or incomplete regeneration, refers to the physiologic adaptation of an organ after injury in an effort to re-establish continuity without regards to exact replacement of lost/damaged tissue.[55] True tissue regeneration or complete regeneration,[56] refers to the replacement of lost/damaged tissue with an 'exact' copy, such that both morphology and functionality are completely restored.[56] Though after injury mammals can completely regenerate spontaneously, they usually do not completely regenerate. An example of a tissue regenerating completely after an interruption of morphology is the endometrium; the endometrium after the process of breakdown via the menstruation cycle heals with complete regeneration.[57]
In some instances, after a tissue breakdown, such as in skin, a regeneration closer to complete regeneration may be induced by the use of biodegradable (collagen-glycoaminoglycan) scaffolds. These scaffolds are structurally analogous to extracellular matrix (ECM) found in normal/un-injured dermis.[58] Interestingly, fundamental conditions required for tissue regeneration often oppose conditions that favor efficient wound repair, including inhibition of (1) platelet activation, (2) inflammatory response, and (3) wound contraction.[1] In addition to providing support for fibroblast and endothelial cell attachment, biodegradable scaffolds inhibit wound contraction, thereby allowing the healing process to proceed towards a more-regenerative/less-scarring pathway. Pharmaceutical agents have been investigated which may be able to turn off myofibroblast differentiation.[59]
A new way of thinking derived from the notion that heparan sulfates are key player in tissue homeostasis: the process that makes the tissue replace dead cells by identical cells. In wound areas, tissue homeostasis is lost as the heparan sulfates are degraded preventing the replacement of dead cells by identical cells. Heparan sulfate analogues cannot be degraded by all know heparanases and glycanases and bind to the free heparin sulfate binding spots on the ECM, therefore preserving the normal tissue homeostasis and preventing scarring.[60][61][62]
Scarless wound healing[edit]
Scarless wound healing is a concept based on the healing or repair of the skin (or other tissue/organs) after injury with the aim of healing with subjectively and relatively less scar tissue than normally expected. Scarless healing is sometimes mixed up with the concept of scar free healing, which is wound healing which results in absolutely no scar (free of scarring). However they are both two different concepts.
A reverse to scarless wound healing is scarification (wound healing to scar more). Historically, certain cultures consider scarification attractive,[63] however, this is generally not the case in the modern western society, in which many patients are turning to plastic surgery clinics with unrealistic expectations. Depending on scar type, treatment may be invasive (intralesional steroid injections, surgery) and/or conservative (compression therapy, topical silicone gel, brachytherapy, photodynamic therapy).[64] Clinical judgment is necessary to successfully balance the potential benefits of the various treatments available against the likelihood of a poor response and possible complications resulting from these treatments. Many of these treatments may only have a placebo effect, and the evidence base for the use of many current treatments is poor.[65]
In the last few decades, comprehension of the basic biologic processes involved in wound repair and tissue regeneration have expanded due to advances in cellular and molecular biology.[66] Currently, the principal goals in wound management are to achieve rapid wound closure with a functional tissue that has minimal aesthetic scaring.[67] However, the ultimate goal of wound healing biology is to induce a more perfect reconstruction of the wound area. Scarless wound healing only occurs in mammalian foetal tissues [68] and complete regeneration is limited to lower vertebrates, such as salamanders, and invertebrates.[69] In adult humans, injured tissue are repaired by collagen deposition, collagen remodelling and eventual scar formation, where fetal wound healing is believed to be more of a regenerative process with minimal or no scar formation.[68] Therefore, foetal wound healing can be used to provide an accessible mammalian model of an optimal healing response in adult human tissues. Clues as to how this might be achieved come from studies of wound healing in embryos, where repair is fast and efficient and results in essentially perfect regeneration of any lost tissue.
The etymology of the term scarless wound healing has a long history.[70][71][72] In print the antiquated concept of scarless healing was brought up the early 20th century and appeared in a paper published in the London Lancet. This process involved cutting in a surgical slant, instead of a right angle…; it was described in various Newspapers.[70][71][72]
Simulating wound healing from a growth perspective[edit]
Considerable effort has been devoted to understanding the physical relationships governing wound healing and subsequent scarring, with mathematical models and simulations developed to elucidate these relationships.[73] The growth of tissue around the wound site is a result of the migration of cells and collagen deposition by these cells. The alignment of collagen describes the degree of scarring; basket-weave orientation of collagen is characteristic of normal skin, whereas aligned collagen fibers lead to significant scarring.[74] It has been shown that the growth of tissue and extent of scar formation can be controlled by modulating the stress at a wound site.[75]
The growth of tissue can be simulated using the aforementioned relationships from a biochemical and biomechanical point of view. The biologically active chemicals that play an important role in wound healing are modeled with Fickian diffusion to generate concentration profiles. The balance equation for open systems when modeling wound healing incorporates mass growth due to cell migration and proliferation. Here the following equation is used:
Dtρ0 = Div (R) + R0,
where ρ represents mass density, R represents a mass flux (from cell migration), and R0 represents a mass source (from cell proliferation, division, or enlargement).[76]
Primary intention[edit]
- When wound edges are brought together (sutured/glued) so that they are adjacent to each other (re-approximated)
- Minimizes scarring
- Most surgical wounds heal by primary intention healing
- Wound closure is performed with sutures (stitches), staples, or adhesive tape or glue.
- Examples: well-repaired lacerations, well reduced bone fractures, healing after flap surgery
Secondary intention[edit]
- The wound is allowed to granulate
- Surgeon may pack the wound with a gauze or use a drainage system
- Granulation results in a broader scar
- Healing process can be slow due to presence of drainage from infection
- Wound care must be performed daily to encourage wound debris removal to allow for granulation tissue formation
- Examples: gingivectomy, gingivoplasty, tooth extraction sockets, poorly reduced fractures.
Tertiary intention[edit]
(Delayed primary closure or secondary suture):
- The wound is initially cleaned, debrided and observed, typically 4 or 5 days before closure.
- The wound is purposely left open
- Examples: healing of wounds by use of tissue grafts.
If the wound edges are not reapproximated immediately, delayed primary wound healing transpires. This type of healing may be desired in the case of contaminated wounds. By the fourth day, phagocytosis of contaminated tissues is well underway, and the processes of epithelization, collagen deposition, and maturation are occurring. Foreign materials are walled off by macrophages that may metamorphose into epithelioid cells, which are encircled by mononuclear leukocytes, forming granulomas. Usually the wound is closed surgically at this juncture, and if the "cleansing" of the wound is incomplete, chronic inflammation can ensue, resulting in prominent scarring.
Overview of involved growth factors[edit]
Following are the main growth factors involved in wound healing:
Growth factor | Abbreviation | Main origins | Effects |
Epidermal growth factor | EGF |
Transforming growth factor-α | TGF-α |
Hepatocyte growth factor | HGF |
Vascular endothelial growth factor | VEGF |
Platelet derived growth factor | PDGF |
Fibroblast growth factor 1 and 2 | FGF-1, −2 |
Transforming growth factor-β | TGF-β |
Keratinocyte growth factor | KGF |
Unless else specified in boxes, then reference is:[77] |
Complications of Wound Healing[edit]
This section may require cleanup to meet Wikipedia's quality standards. (April 2012) |
The major complications are many:
- Deficient Scar Formation: Result in wound dehiscence or rupture of the wound due to inadequate formation of granulation tissue.
- Excessive Scar Formation: Hypertrophic scar, Keloid, Desmoid.
- Exuberant Granulation (Proud flesh).
- Deficient Contraction (in skin grafts) or excessive contraction (in burns).
- Others: Dystrophic calcification, pigmentary changes, painful scars, inscisional hernia etc.
See also[edit]
Notes and references[edit]
- ^ a b c d e f g h i j k Nguyen, D.T., Orgill D.P., Murphy G.F. (2009). Chapter 4: The Pathophysiologic Basis for Wound Healing and Cutaneous Regeneration. Biomaterials For Treating Skin Loss. Woodhead Publishing (UK/Europe) & CRC Press (US), Cambridge/Boca Raton, p. 25-57. (ISBN 978-1-4200-9989-8/ISBN 978-1-84569-363-3)
- ^ a b c d e f g h i j k l m Stadelmann, WK; Digenis, AG; Tobin, GR (1998). "Physiology and healing dynamics of chronic cutaneous wounds". American journal of surgery 176 (2A Suppl): 26S–38S. doi:10.1016/S0002-9610(98)00183-4. PMID 9777970.
- ^ Quinn, J.V. (1998). Tissue Adhesives in Wound Care. Hamilton, Ont. B.C. Decker, Inc. Electronic book.
- ^ Poquérusse, Jessie. "The Neuroscience of Sharing". Retrieved 16 August 2012.
- ^ a b c d e f g h Midwood, K.S.; Williams, L.V.; Schwarzbauer, J.E. (2004). "Tissue repair and the dynamics of the extracellular matrix". The International Journal of Biochemistry & Cell Biology 36 (6): 1031–1037. doi:10.1016/j.biocel.2003.12.003. PMID 15094118.
- ^ Chang, HY; Sneddon, JB; Alizadeh, AA; Sood, R; West, RB; Montgomery, K; Chi, JT; Van De Rijn, M et al. (2004). "Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds". PLoS Biology 2 (2): E7. doi:10.1371/journal.pbio.0020007. PMC 314300. PMID 14737219.
- ^ Garg, H.G. (2000). Scarless Wound Healing. New York Marcel Dekker, Inc. Electronic book.
- ^ Enoch, S. Price, P. (2004). Cellular, molecular and biochemical differences in the pathophysiology of healing between acute wounds, chronic wounds and wounds in the elderly. http://www.worldwidewounds.com/2004/august/Enoch/Pathophysiology-Of-Healing.html
- ^ Reference list is found on image main page.
- ^ Galko MJ, Krasnow MA (2004). "Cellular and genetic analysis of wound healing in Drosophila Larvae". PLoS Biology 2 (8): e239. doi:10.1371/journal.pbio.0020239. PMC 479041. PMID 15269788.
- ^ a b c d e Rosenberg L., de la Torre J. (2006). Wound Healing, Growth Factors. Emedicine.com. Accessed January 20, 2008.
- ^ Sandeman, S.R.; Allen, M.C.; Liu, C.; Faragher, R.G.A.; Lloyd, A.W. (2000). "Human keratocyte migration into collagen gels declines with in vitro ageing". Mechanisms of Ageing and Development 119 (3): 149–157. doi:10.1016/S0047-6374(00)00177-9. PMID 11080534.
- ^ a b c d Dealey C. (1999). The care of wounds: A guide for nurses. Oxford ; Malden, Mass. Blackwell Science. Electronic book.
- ^ Theoret, C.L. (2004). "Update on wound repair". Clinical Techniques in Equine Practice 3 (2): 110–122. doi:10.1053/j.ctep.2004.08.009.
- ^ a b c d e f g h de la Torre J., Sholar A. (2006). Wound healing: Chronic wounds. Emedicine.com. Accessed January 20, 2008.
- ^ a b c d e f g h Greenhalgh, D.G. (1998). "The role of apoptosis in wound healing". The International Journal of Biochemistry & Cell Biology 30 (9): 1019–1030. doi:10.1016/S1357-2725(98)00058-2. PMID 9785465.
- ^ Muller, M.J.; Hollyoak, M.A.; Moaveni, Z.; La, T.; Brown, H.; Herndon, D.N.; Heggers, J.P. (2003). "Retardation of wound healing by silver sulfadiazine is reversed by Aloe vera and nystatin". Burns 29 (8): 834–836. doi:10.1016/S0305-4179(03)00198-0. PMID 14636760.
- ^ Martin, P.; Leibovich, SJ (2005). "Inflammatory cells during wound repair: the good, the bad and the ugly". Trends in Cell Biology 15 (11): 599–607. doi:10.1016/j.tcb.2005.09.002. PMID 16202600.
- ^ a b c d e f g h Santoro, M.M.; Gaudino, G. (2005). "Cellular and molecular facets of keratinocyte reepithelization during wound healing". Experimental Cell Research 304 (1): 274–286. doi:10.1016/j.yexcr.2004.10.033. PMID 15707592.
- ^ a b Expert Reviews in Molecular Medicine. (2003). The phases of cutaneous wound healing. 5: 1. Cambridge University Press. Accessed January 20, 2008.
- ^ a b c d e f Deodhar, AK; Rana, RE (4/1/1997). "Surgical physiology of wound healing: a review". Journal of Postgraduate Medicine 43 (2): 52–6. PMID 10740722.
- ^ Ovchinnikov, Dmitry A. (2008). Macrophages in the embryo and beyond: Much more than just giant phagocytes. Institute for Molecular Bioscience and Cooperative Research Centre for Chronic Inflammatory Diseases (CRC-CID), University of Queensland, Brisbane, Queensland, Australia.: researchgate.net. doi:10.1002/dvg.20417. Retrieved 2013-06-28. "Macrophages are present essentially in all tissues, beginning with embryonic development and, in addition to their role in host defense and in the clearance of apoptotic cells, are being increasingly recognized for their trophic function and role in regeneration."
- ^ a b c d Newton, P. M.; Watson, J. A.; Wolowacz, R. G.; Wood, E. J. (2004). "Macrophages Restrain Contraction of an In Vitro Wound Healing Model". Inflammation 28 (4): 207–14. doi:10.1023/B:IFLA.0000049045.41784.59. PMID 15673162.
- ^ a b c d e f g h Mercandetti M., Cohen A.J. (2005). Wound Healing: Healing and Repair. Emedicine.com. Accessed January 20, 2008.
- ^ Stashak, T.S.; Farstvedt, E.; Othic, A. (2004). "Update on wound dressings: Indications and best use". Clinical Techniques in Equine Practice 3 (2): 148–163. doi:10.1053/j.ctep.2004.08.006.
- ^ Swirski, F. K.; Nahrendorf, M.; Etzrodt, M.; Wildgruber, M.; Cortez-Retamozo, V.; Panizzi, P.; Figueiredo, J.-L.; Kohler, R. H. et al. (2009). "Identification of Splenic Reservoir Monocytes and Their Deployment to Inflammatory Sites". Science 325 (5940): 612–616. Bibcode:2009Sci...325..612S. doi:10.1126/science.1175202. PMC 2803111. PMID 19644120.
- ^ Jia, T.; Pamer, E. G. (2009). "Dispensable But Not Irrelevant". Science 325 (5940): 549–550. Bibcode:2009Sci...325..549J. doi:10.1126/science.1178329. PMC 2917045. PMID 19644100.
- ^ a b c d e f g h i Lorenz H.P. and Longaker M.T. (2003). Wounds: Biology, Pathology, and Management. Stanford University Medical Center. Accessed January 20, 2008.
- ^ a b c d e Hinz, B (2006). "Masters and servants of the force: the role of matrix adhesions in myofibroblast force perception and transmission". European Journal of Cell Biology 85 (3–4): 175–81. doi:10.1016/j.ejcb.2005.09.004. PMID 16546559.
- ^ Souppouris, Aaron (2013-05-23). "Scientists identify cell that could hold the secret to limb regeneration". the verge.com. "Researchers have identified a cell that aids limb regrowth in Salamanders. Macrophages are a type of repairing cell that devour dead cells and pathogens, and trigger other immune cells to respond to pathogens."
- ^ James W. Godwin, Alexander R. Pinto, and Nadia A. Rosenthal (2013-04-24). "Macrophages are required for adult salamander limb regeneration". University of Texas.
- ^ a b c d Falanga V. (2005). Wound Healing. American Academy of Dermatology (AAD).
- ^ a b c Kuwahara R.T. and Rasberry R. 2007. Chemical Peels. Emedicine.com. Accessed September 15, 2007.
- ^ a b c d e f g h i j Romo T. and Pearson J.M. 2005. Wound Healing, Skin. Emedicine.com. Accessed December 27, 2006.
- ^ Lansdown, A.B.G.; Sampson, B.; Rowe, A. (2001). "Experimental observations in the rat on the influence of cadmium on skin wound repair". International Journal of Experimental Pathology 82 (1): 35–41. doi:10.1046/j.1365-2613.2001.00180.x. PMC 2517695. PMID 11422539.
- ^ a b c d Song, G; Nguyen, DT; Pietramaggiori, G; Scherer, S; Chen, B; Zhan, Q; Ogawa, R; Yannas, IV et al. (2010). "Use of the parabiotic model in studies of cutaneous wound healing to define the participation of circulating cells". Wound Repair and Regeneration 18 (4): 426–432. doi:10.1111/j.1524-475X.2010.00595.x. PMC 2935287. PMID 20546556.
- ^ Ruszczak, Z. (2003). "Effect of collagen matrices on dermal wound healing". Advanced Drug Delivery Reviews 55 (12): 1595–1611. doi:10.1016/j.addr.2003.08.003. PMID 14623403.
- ^ a b Fig. 9-1. The cellular, biochemical, and mechanical phases of wound healing. Pollock, Raphael E.; F. Charles Brunicardi; Dana K. Andersen; Billiar, Timothy R.; Dunn, David; Hunter, John G.; Matthews, Jeffrey J. (2009). Schwartz's Principles of Surgery, Ninth Edition. McGraw-Hill Professional. ISBN 0-07-154769-X.
- ^ a b c d e f g h DiPietro L.A. and Burns A.L., Eds. 2003. Wound Healing: Methods and Protocols. Methods in Molecular Medicine. Totowa, N.J. Humana Press. Electronic book.
- ^ Fu, Xiao-bing; Sun, Tong-zhu; Li, Xiao-kun; Sheng, Zhi-yong (2005). "Morphological and distribution characteristics of sweat glands in hypertrophic scar and their possible effects on sweat gland regeneration". Chinese Medical Journal 118 (3): 186–91. PMID 15740645.
- ^ a b c d Bartkova, Jirina; Grøn, Birgitte; Dabelsteen, Erik; Bartek, Jiri (2003). "Cell-cycle regulatory proteins in human wound healing". Archives of Oral Biology 48 (2): 125–32. doi:10.1016/S0003-9969(02)00202-9. PMID 12642231.
- ^ a b c d Mulvaney M. and Harrington A. 1994. Chapter 7: Cutaneous trauma and its treatment. In, Textbook of Military Medicine: Military Dermatology. Office of the Surgeon General, Department of the Army. Virtual Naval Hospital Project. Accessed through web archive on September 15, 2007.
- ^ a b c d Larjava H., Koivisto L., and Hakkinen L. 2002. Chapter 3: Keratinocyte Interactions with Fibronectin During Wound Healing. In, Heino, J. and Kahari, V.M. Cell Invasion. Medical Intelligence Unit ; 33. Georgetown, Tex., Austin, Tex Landes Bioscience, Inc. Electronic book.
- ^ Witte, Maria B; Barbul, Adrian (2002). "Role of nitric oxide in wound repair". The American Journal of Surgery 183 (4): 406–12. doi:10.1016/S0002-9610(02)00815-2. PMID 11975928.
- ^ Son, Hyun Joo; Bae, Hyun Chul; Kim, Hyun Jeong; Lee, Dong Hee; Han, Dong-Wook; Park, Jong-Chul (2005). "Effects of β-glucan on proliferation and migration of fibroblasts". Current Applied Physics 5 (5): 468–71. Bibcode:2005CAP.....5..468S. doi:10.1016/j.cap.2005.01.011.
- ^ Falanga, Vincent (2004). "The chronic wound: Impaired healing and solutions in the context of wound bed preparation". Blood Cells, Molecules, and Diseases 32 (1): 88–94. doi:10.1016/j.bcmd.2003.09.020. PMID 14757419.
- ^ Etscheid, M.; Beer, N.; Dodt, J. (2005). "The hyaluronan-binding protease upregulates ERK1/2 and PI3K/Akt signalling pathways in fibroblasts and stimulates cell proliferation and migration". Cellular Signalling 17 (12): 1486–94. doi:10.1016/j.cellsig.2005.03.007. PMID 16153533.
- ^ Bayram, Yalcin; Deveci, Mustafa; Imirzalioglu, Nejat; Soysal, Yasemin; Sengezer, Mustafa (2005). "The cell based dressing with living allogenic keratinocytes in the treatment of foot ulcers: A case study". British Journal of Plastic Surgery 58 (7): 988–96. doi:10.1016/j.bjps.2005.04.031. PMID 16040019.
- ^ Grinnell, F. (1994). "Fibroblasts, myofibroblasts, and wound contraction". J. Cell Biol 124 (4): 401–404. doi:10.1083/jcb.124.4.401. PMC 2119916. PMID 8106541.
- ^ a b Eichler, MJ; Carlson, MA (2006). "Modeling dermal granulation tissue with the linear fibroblast-populated collagen matrix: a comparison with the round matrix model". Journal of dermatological science 41 (2): 97–108. doi:10.1016/j.jdermsci.2005.09.002. PMID 16226016.
- ^ a b c d Mirastschijski, U.; Haaksma, C.J.; Tomasek, J.J.; Ågren, M.S. (2004). "Matrix metalloproteinase inhibitor GM 6001 attenuates keratinocyte migration, contraction and myofibroblast formation in skin wounds". Experimental Cell Research 299 (2): 465–475. doi:10.1016/j.yexcr.2004.06.007. PMID 15350544.
- ^ worldwidewounds.com > Figure 3 – The time relationship between the different processes of wound healing. by Gregory S Schultz, Glenn Ladwig and Annette Wysocki – in turn adapted from Asmussen PD, Sollner B. Mechanism of wound healing. In: Wound Care. Tutorial Medical Series. Stuttgart: Hippokrates Verlag, 1993.
- ^ O'Leary, R; Wood, EJ; Guillou, PJ (2002). "Pathological scarring: Strategic interventions". The European journal of surgery 168 (10): 523–34. PMID 12666691.
- ^ Desmoulière, Alexis; Chaponnier, Christine; Gabbiani, Giulio (2005). "Tissue repair, contraction, and the myofibroblast". Wound Repair and Regeneration 13 (1): 7–12. doi:10.1111/j.1067-1927.2005.130102.x. PMID 15659031.
- ^ a b c d Min, Su; Wang, Song W.; Orr, William (2006). "Graphic general pathology: 2.3 Incomplete regeneration:". Pathology. pathol.med.stu.edu.cn. Retrieved 2012-12-07. "The new tissue is not the same as the tissue that was lost. After the repair process has been completed, there is a loss in the structure or function of the injured tissue. In this type of repair, it is common that granulation tissue (stromal connective tissue) proliferates to fill the defect created by the necrotic cells. The necrotic cells are then replaced by scar tissue."
- ^ a b c d Min, Su; Wang, Song W.; Orr, William (2006). "Graphic general pathology: 2.2 complete regeneration:". Pathology. pathol.med.stu.edu.cn. Retrieved 2012-12-07. "(1) Complete regeneration: The new tissue is the same as the tissue that was lost. After the repair process has been completed, the structure and function of the injured tissue are completely normal"
- ^ a b c Min, Su; Wang, Song W.; Orr, William (2006). "Graphic general pathology: 2.2 complete regeneration:". Pathology. pathol.med.stu.edu.cn. Retrieved 2013-11-10. "After the repair process has been completed, the structure and function of the injured tissue are completely normal. This type of regeneration is common in physiological situations. Examples of physiological regeneration are the continual replacement of cells of the skin and repair of the endometrium after menstruation. Complete regeneration can occur in pathological situations in tissues that have good regenerative capacity."
- ^ Yannas, I. V.; Lee, E; Orgill, DP; Skrabut, EM; Murphy, GF (1989). "Synthesis and Characterization of a Model Extracellular Matrix that Induces Partial Regeneration of Adult Mammalian Skin". Proceedings of the National Academy of Sciences 86 (3): 933–7. Bibcode:1989PNAS...86..933Y. doi:10.1073/pnas.86.3.933. JSTOR 33315. PMC 286593. PMID 2915988.
- ^ O'Leary, R.; Ponnambalam, S.; Wood, E.J. (2003). "Pioglitazone-induced myofibroblast cell death: Implications for cutaneous scarring". British Journal of Dermatology 149 (3): 665–7. doi:10.1046/j.1365-2133.2003.05501.x. PMID 14511015.
- ^ Tong, Miao; Tuk, Bastiaan; Hekking, Ineke M.; Vermeij, Marcel; Barritault, Denis; Van Neck, Johan W. (2009). "Stimulated neovascularization, inflammation resolution and collagen maturation in healing rat cutaneous wounds by a heparan sulfate glycosaminoglycan mimetic, OTR4120". Wound Repair and Regeneration 17 (6): 840–52. doi:10.1111/j.1524-475X.2009.00548.x. PMID 19903305.
- ^ Barritault, D.; Caruelle, J.-P. (2006). "Les agents de régénération (ou RGTAs) : Une nouvelle approche thérapeutique" [Regenerating agents (RGTAs): a new therapeutic approach]. Annales Pharmaceutiques Françaises (in French) 64 (2): 135–44. doi:10.1016/S0003-4509(06)75306-8. PMID 16568015.
- ^ Van Neck et al, Heparan sulfate proteoglycan mimetics thrive tissue regeneration: an overview. In Intech book under the working title "Tissue Regeneration", ISBN 978-953-307-876-2 is scheduled for on line publication on Nov 26, 2011"[page needed]
- ^ Rush, J. (2005). Spiritual tattoo: a cultural history of tattooing, piercing, scarification, branding, and implants, Frog Ltd.
- ^ Brown, B., Mckenna, S., Siddhi, K., Mcgrouther, D. & Bayat, A. (2008). The hidden cost of skin scars: quality of life after skin scarring. Journal of Plastic, Reconstructive & Aesthetic Surgery, 61, 1049-1058.
- ^ Bayat, A., Mcgrouther, D. & Ferguson, M. (2003). Skin scarring. Bmj, 326, 88.
- ^ Clark, R. (1996). The molecular and cellular biology of wound repair, Springer Us.
- ^ Tonnesen, M. G., Feng, X. & Clark, R. A. (2000). Angiogenesis in wound healing. J Investig Dermatol Symp Proc, 5, 40-46.
- ^ a b Ferguson, M., Whitby, D., Shah, M., Armstrong, J., Siebert, J. & Longaker, M. (1996). Scar formation: the spectral nature of fetal and adult wound repair. Plastic and reconstructive surgery, 97, 854.
- ^ Brockes, J., Kumar, A. & Velloso, C. (2001). Regeneration as an evolutionary variable. Journal of Anatomy, 199, 3-11.
- ^ a b "Scarless Healing". Star (Christchurch, New Zealand: Star). 1906-07-07. pp. Page 4. Retrieved 2013-07-02.
- ^ a b "Scarless Healing". Marlborough Express, Volume XXXIX, Issue 160, (paperspast.natlib.govt.nz). 1906-07-12. pp. Page 1. Retrieved 2013-07-02.
- ^ a b "A Wonderful New Surgery". Reading Eagle. 1906-07-06. pp. Page 6. Retrieved 2013-07-02.
- ^ Cumming, B. D.; McElwain, D. L. S.; Upton, Z. (2009). "A mathematical model of wound healing and subsequent scarring". Journal of the Royal Society Interface 7 (42): 19–34. doi:10.1098/rsif.2008.0536. PMC 2839370. PMID 19324672.
- ^ Gurtner, Geoffrey C.; Werner, Sabine; Barrandon, Yann; Longaker, Michael T. (2008). "Wound repair and regeneration". Nature 453 (7193): 314–21. Bibcode:2008Natur.453..314G. doi:10.1038/nature07039. PMID 18480812.
- ^ Gurtner, Geoffrey C.; Dauskardt, Reinhold H.; Wong, Victor W.; Bhatt, Kirit A.; Wu, Kenneth; Vial, Ivan N.; Padois, Karine; Korman, Joshua M. et al. (2011). "Improving Cutaneous Scar Formation by Controlling the Mechanical Environment". Annals of Surgery 254 (2): 217–25. doi:10.1097/SLA.0b013e318220b159. PMID 21606834.
- ^ Kuhl, E.; Steinmann, P. (2004). "Computational modeling of healing: An application of the material force method". Biomechanics and Modeling in Mechanobiology 2 (4): 187–203. doi:10.1007/s10237-003-0034-3. PMID 14872320.
- ^ Table 3-1 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7. 8th edition.
External links[edit]
This article's use of external links may not follow Wikipedia's policies or guidelines. (February 2013) |
- Wound Healing Society
- European Tissue Repair Society
- Wound Repair and Regeneration The official publication of the Wound Healing Society and the European Tissue Repair Society.
- Journal of Burns and Wounds
- Fibrogenesis & Tissue Repair, an online open access journal about chronic wound healing and fibrogenesis.
- EWMA Journal, Journal of the European Wound Management Association
- Grace Bio-Labs, Wound Repair Article Links


text:
Many knitting patterns that involve shaping, such as sweaters and vests that decrease gradually through the armhole, will include this or a similar phrase: Decrease at the beginning and end of every fourth row, maintaining pattern as established. This is easy enough to understand if you're working stockinette stitch -- simply decrease stitches as instructed and continue knitting all right-side rows and purling all wrong-side rows.
While it's easy to understand this in theory, it may not be obvious how to do this for complicated stitch patterns. If you're going to sew your seam with mattress stitch, you need to keep one edge stitch in stockinette stitch throughout and make your decreases after the beginning edge stitch and before the ending edge stitch. Let's look at a couple of examples.
Our example is a 2x2 rib that begins with two knit stitches on each end. The first and last knit stitches are edge stitches, so the first decrease will be worked over the second knit stitch and the following purl stitch. If you work p2tog here, you'll end up with one edge stitch followed by p2, k2, etc. At the other end of the row you'll work the decrease over the third stitch from the end, which is a purl stitch, and the second-to-last stitch, which is a knit stitch. This would be worked as ssp (slip 1, slip 1, purl the two slipped stitches together).
Here's how you would work a series of decreases on 2x2 rib, decreasing every fourth row.
Photo 1: Decreasing as described keeps all the rib columns orderly. |
Row 1: K1, p2tog, p1, k2, *p2, k2; rep from * to last 4 sts, p1, ssp, k1.
Rows 2-4: Knit the knits and purl the purls.
Row 5: K1, p2tog, k2, *p2, k2; rep from * to last 4 sts, ssp, k1.
Rows 6-8: Knit the knits and purl the purls.
Row 9: K1, k2tog, k1, *p2, k2; rep from * to last 6 sts, p2, k1, ssk, k1.
Rows 10-12: Knit the knits and purl the purls.
Row 13: K1, k2tog, *p2, k2; rep from * to last 5 sts, p2, ssk, k1.
Rows 14-16: Knit the knits and purl the purls.
Repeat these 16 decrease rows as necessary.
Photo 1 shows this series of decreases worked once.
Let's say you're working an allover 3x3 left-crossing cable with two purl stitches between. If you stop turning the cables as soon as you no longer have a full count of six stitches, you'll end up with rather large blocks of stockinette stitch above the outer cables (see Photo 2). This may not bother you, and that's fine.
However, you can continue working stitches into pattern when you are left with five or four. On the cable-turning row where you have only five stitches for the cable, place three stitches on a cable needle and hold in front, knit two, then knit three from the cable needle. To work the cable over four stitches, place three stitches on a cable needle and hold in front, knit one, then knit three from the cable needle. And if you want to maintain texture when you have only three stitches left for a cable, you could work a two-over-one cable (see Photo 3).
If your decrease row coincides with a cable-turning row, and you have a cable right at the edge (being sure you've left an edge stitch for seaming), you can place three stitches on a cable needle and hold in front, knit two together, knit one, then knit three from the cable needle.
Things can become a bit more complicated when you're decreasing in a lace or other complex stitch pattern. These have to be figured out on a case-by-case basis. Here's an example of a lace pattern that's a multiple of 12 + 1 stitches with an edge stitch on both sides. The Chart 1 shows the pattern intact, and Chart 2 shows how you would work the decreases to get the correct number of stitches and stay in pattern as closely as possible.
Chart 1: Here is the chart worked without decreases. |
Chart 2: The decreases are worked so as to maintain pattern as closely as possible. |
Chart Key |
Photo 4: The pattern is maintained through the decrease rows. |
The first decrease is on Row 2, and it's worked by making a double decrease where a single decrease is called for in the pattern at the beginning and end of the row. The same technique is used on Row 6. When we get to Row 10 we've already eliminated two of the four pattern stitches at the beginning and end of the row. If we work the remaining decrease without the corresponding yarn over, we've accomplished the goal of reducing one more stitch.
Every scenario will be a little different, but with a little ingenuity, you can maintain your lovely patterns while decreasing (see Photo 4).

subset: commoncrawl


text:
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March 9, 2012 5:06 am | Product Releases | CommentsMolex Incorporated introduced SlimStack B8 connectors, featuring a robust housing and unique CleanPoint contact for removing flux and other contaminants to provide desirable electrical reliability. These 0.40-mm pitch SMT board-to-board connectors, with a 0.80-mm height and ultra-narrow 2.50-mm width are appropriate in high end medical, consumer electronics, data/telecom and mobile device applications.
LISTED UNDER: Interconnect, ConnectorsWaterproof and Standard RF Connectors for Medical Applications
March 1, 2012 4:49 am | by For more information, please visit www.intelliconnectusa.com . Posted Ron M. Seidel, Editorial Intern March 1, 2012 | Product Releases | CommentsDesigned and manufactured in the USA, fast turnaround standard and custom designs Intelliconnect now offers their fast turnaround custom design service for non-standard medical connectors used in specialized medical products. Typical turnaround time is 7-8 weeks. Intelliconnect does not charge NRE and has low minimum order quantities.
LISTED UNDER: Medical | Interconnect, ConnectorsSmall Two Piece Battery Connectors with Two Way Insertion
January 17, 2012 7:28 am | Product Releases | CommentsDue to popular demand, Yokowo's two piece battery connectors has expanded and now will include a compact version. Featuring two less blades than the original 6-blade type, the new 4 blade model is designed to also allow for flexibility for both horizontal and vertical blade insertion. The compact size has also resulted in a reduction in pitch (from 3mm to 2.
LISTED UNDER: Interconnect, Connectors | Power, Batteries | Power, BatteryCN074 AdvancedMC Connectors for AdvancedTCA
October 20, 2011 6:28 am | Product Releases | Comments- Compression Mount Contacts (CMT) - High speed transmission 12.5 Gbps - Complete product range: B, B+, AB, A+B+ - Integrated YFLEX technology - Customized pin assignment possible - Acc. to PICMG Spec. ATCA 3.0 R2.0 Insulation Resistance 100MO min.
LISTED UNDER: Interconnect, ConnectorsTwo Piece Battery Connectors with Two Way Insertion
October 12, 2011 11:18 am | by Posted Janine E. Mooney, Associate Editor | Product Releases | CommentsYokowo's new two piece battery connector allows both horizontal and vertical blade insertion, as well as increased flexibility in designs. For reliability, the receptacle side features dual beam contact in both insertion directions. Two tabs are uniquely fitted on the receptacle to provide a secure grip around the blade upon insertion.
LISTED UNDER: Interconnect, Connectors | Power, Batteries | Power, BatteryUK Made Custom RF Connectors Delivered in 7 Weeks
September 22, 2011 12:33 pm | Product Releases | CommentsIntelliconnect, the UK based manufacturer of RF connectors, offers one of the widest ranges of standard Coaxial, Triaxial and Waterproof connectors available worldwide. In addition, their extensive design experience and UK sourced components allows Intelliconnect to offer an unrivalled custom connector design service.
LISTED UNDER: Interconnect, ConnectorsRF Connectors on show at European Microwave Week
August 24, 2011 4:52 am | Product Releases | CommentsIntelliconnect (Europe) Ltd, the only UK manufacturer of 50? Coaxial and Triaxial RF connectors will be at the European Microwave Week in October supporting their UK Technical Representative UKRF. At the Manchester based show Intelliconnect products will be found on stand number 618. UKRF Managing Director Peter Frost comments;" Intelliconnect, with their unique approach to the connectivity market, have enabled UKRF to offer timely and cost effective solutions to our customer's connectivity problems.
LISTED UNDER: Interconnect, ConnectorsConnectors Ideal for Numerous Power Bus Applications
August 9, 2011 6:26 am | Product Releases | CommentsAmphenol Industrial now offers three compact, high-amperage, ROHS-compliant RADSOK PCB connectors for a variety of power bus applications. These applications include, but are not limited to, high-power bus assembly utilities, power-to-board servers, power-to-box servers and battery power/chargers for electric vehicles.
LISTED UNDER: Interconnect, ConnectorsDownhole Pigtails on KTK Connectors Eliminate Need to Wire and Solder
July 15, 2011 7:32 am | Product Releases | CommentsAmphenol Industrial has enhanced its KTK connectors with downhole microD pigtails. These new pigtails, manufactured according to customer specification and direction, eliminate the costly and tedious task of wiring and soldering Amphenol's KTKs to microDs, saving both time and money. Featuring a bi-directional psi of 20,000, Amphenol's KTK high pressure downhole connectors for oil and gas downhole tools offer a high pressure and high temperature sealed connection standard in the downhole industry.
LISTED UNDER: Interconnect, Connectors


text: Welcome from Ryan GremoreWelcome to the internet home of the O'Brien Automotive Team, proudly serving the Normal area with quality new and used cars and award-winning service. Our new website is part of our commitment to excellence and our dedication to providing O'Brien Team customers convenient 24-hour access to useful information and satisfying service.We are proud of our new cars and their reputation for value, quality and reliability and our O'Brien Certified Best Used Cars must pass rigid standards before they are available for sale. Certified Best Used Cars are backed by a two-day money back offer, a two-week exchange policy, and a two-month/2,000 mile limited warranty - all unique to the automobile industry. Our customers have high expectations for their vehicles, and equally high expectations about the dealership professionals who serve them. Every member of the O'Brien team, from the receptionist at the front counter to the technicians in our well-equipped shop, is committed to providing you with an enjoyable experience to guarantee your satisfaction. With online access to our many quality new cars, trucks, vans, SUVs and crossovers, our huge selection of premium used cars, online specials and promotions and aggressive factory incentives, we're sure you'll find what you've been looking for at our website. Get a quick quote, learn the value of your trade, research financing options or contact our sales department with the click of your mouse. You may also browse our service and parts department pages to schedule an appointment and to order parts and accessories. And if you feel more comfortable dealing with us personally, give us a call, email us or visit our dealership at anytime for additional customer support. Click on the information tab for our business hours, phone numbers and driving directions to our store location, or to learn more about your preferred make and model. While we have taken special care to make sure the site is fast, accurate and the information you need is only a click away, nothing we can do here comes close to the friendly personal service you will find at our dealership. We are committed to building long term relationships with our customers and business partners based on honesty, fairness, trust and mutual respect. We consider our people our most valuable asset and we are dedicated to serving our community in every way possible. If you have any questions, you can always call us at 888-483-3446. That is just how we do business. We are here to help. Additionally, you can email us with questions or to request an appointment. Click the Contact Us link at on menu. Ryan Gremore Vice President and General Manager |


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Full forecast and current conditions are always available on your mobile device.
Click here to download our StormTrack Mobile App.
A fourth man sought by Bowling Green Police in a late August kidnapping turned himself in on Tuesday.
BG Police say 19-year-old Nicholas Martinez surrendered himself in Bowling Green Municipal Court on Tuesday morning. Martinez was the last of four suspects to be arrested for the kidnapping of a University of Toledo student which began in Toledo, continued to Bowling Green and ended in Holland, Ohio.
Blake Long, Brittany Long and Hui Zang were previously arrested in the case. Bowling Green Police say the four lured a Chinese University of Toledo student into their vehicle with the promise of a ride to Cedar Point, then drove him to Bowling Green and stole his credit cards. The four then drove the student to the EconoLodge in Holland, Ohio and attempted to solicit ransom from his relatives in China, police said.
Tune in to WTOL 11 News at 5 for more on this breaking news story.
Copyright 2013 Toledo News Now. All rights reserved.


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BnB Tobacco's online hookah and shisha shop offers a variety of discount shisha tobacco from top brands like Acid, Fantasia, Hookah-Hookah and more. On top of this, you will find a large selection of hookah pipes from modern and affordable to traditional and exotic. Our Hookahs are cheap, but only in price! With BNB, you know you are going to get the best quality products at the lowest prices online.
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By Paul Ryan & Becca Church | 12/11/13 6:00 PM
BOSTON (Dec. 11, 2013) – Along with the supplemental draft today (click here to see draft results), some teams were busy making trades. The New York Lizards, Ohio Machine and Chesapeake Bayhawks executed a pair of trades that ultimately saw All-Star defender Kyle Hartzell head to New York for the 2014 season. The Lizards also sent Attackman Matt Gibson to the Denver Outlaws in exchange for midfielder Justin Turri
As part of the Hartzell trade, the Lizards acquired midfielder Kevin Cooper and face off specialistMatt Dolente from the Chesapeake Bayhawks in exchange for the second and 28th selections in the supplemental draft. New York then flipped the two players and the No. 13 pick in the 2014 Collegiate Draft to Ohio for Hartzell.
Hartzell, a six-year veteran of the league, will be playing for his fourth MLL team. The Baltimore, Md., native won a title with Chesapeake in 2010 and was named to the All-Pro Team in 2012. His nine 2-point goals in 2012 were second in the league, trailing only Chesapeake's Kyle Dixon.
Cooper and Dolente, who are headed to Ohio with the 13th pick in the 2014 MLL Collegiate Draft, both finished the year with the 2013 MLL Champion Chesapeake Bayhawks last season. Cooper scored three goals in two games of his first professional season, while faceoff specialist Dolente appeared in seven games.
Initially acquired by Chesapeake in 2012 Gibson will be playing in his third season with the league. In 2012, the attackman played in 12 regular season games, scored 18 goals and recorded 15 assists on his way to being named Cascade Rookie of the Year. Last season he only appeared in six games recording four goals and five assists.
Turri is also entering his third season in the MLL and will be playing for his third team. In 2012 , his debut season, he appeared in eight games for the Charlotte Hounds scoring four goals and adding five assists. In 2013 he appeared in all 14 regular season games for the Outlaws, recording nine goals and four assists.
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Here's our wrap up and summary of the last five Denver Broncos Training Camp practices of 2013!
The most amazing winning streak in Broncos history continues in unbelievable fashion. Tim Tebow, strong defense, and Matt Prater's leg carry the Broncos to their 6th straight victory. Tebow now 7-1 as a starter!
Enjoy this song parody courtesy of Lady GaGa's "Poker Face" after Tim Tebow replaces Kyle Orton as starting QB of the Denver Broncos. Finally some football excitement in Denver again.
With the Broncos deep inside the Titan 5-yard line we pick up Mike McCoy calling in the plays.
Spencer talks about new coach John Fox, his heroes, playing offense and defense, and balancing the NFL and family life.
Meet the newest Denver Bronco wide receiver and return specialist Quan Cosby
These guys must be diehard fans. Looks fun! Good to see Mecklenburg and Mark Jackson again. Cheerleaders are also nice to look at
I can't wait to get this CBA worked out and back to watching diehard Broncos fans like this dude enjoying his afternoon at Invesco Field.
One senior NFL scout has said Von Miller will be a bust. Super Bowl winning coach Jon Gruden says he was the best overall player in the draft. See what this diehard fan has to say about Von Miller being a Stud or a Dud.
Karl Meckenburg talks about his award winning book, playing defense with Dennis Smith and Steve Atwater, what it was like to be on team with John Elway, and being accidently shot in the back of the head. Join us as we chat football, leadership, and good parenting with a Denver Broncos Legend!
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AHS Boys Soccer vs Springtown; V-5:30
The Community News • P.O. Box 1031 • 203 Pecan Dr. • Aledo, TX 76008 • 817-441-7661 • FAX: 817-441-5419
The Aledo Ladycats will play El Paso Chapin in a best-of-three Regional Semifinal Softball Playoff at Ratliff Stadium in Odessa. Game two will be Saturday at 1 p.m. Game three, if necessary, will be 30 minutes following Game two.
AHS Boys Soccer vs Springtown; V-5:30
AHS Girls Soccer vs Springtown; V-7:30
AHS Boys Soccer at Chisholm Trail; JV-7:30 P.M. V-5:30 P.M.
AHS Girls Soccer at Chisholm trail; V-7:30
Aledo Varsity Tennis hosts the Aledo Tournament
Aledo Varsity Tennis at the Crowley Tournament
Aledo Varsity Tennis competes in the District Tournament at TCU


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Raider fans are notorious for making Oakland one of the NFL's most difficult places for a visiting team to play, a reputation that Broncos players enjoyed overcoming.
"There is no better feeling – other than maybe winning the Super Bowl, but I don't know how that feels yet," cornerback Champ Bailey said after the game. "It's awesome, especially for the city of Denver. I know how much they hate the Raiders and so do we. It's good to come in here on their turf and get the win."
"There is no greater feeling in a season than winning here," added linebacker Wesley Woodyard. "This is what it's all about – a true football atmosphere. They hate (us), we hate them. This is what NFL football is all about."
Click to continue reading "Leaving the Black Hole with a Win"


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Discover our New Geriatric Emergency Department
The goal for the geriatric emergency department is to improve healthcare and emergency healthcare for functional and emergent seniors. This is for all of our aging parents, grandparents, and even for ourselves when we finally hit that age of 65 when we'll be eligible to come into the geriatric emergency department.
There are several parts to a geriatric emergency department and one of those is education. Both our nursing staff and our medical staff have been trained on how to manage geriatric illnesses. It also has to do with quality initiatives. We have a call back program, we call it the 2 step emergency department. Not only are patients seen in the emergency department which is step 1 but they're actually re-evaluated the next day at home which is step 2. We have found that the 2 step process actually decreases functional decline in functionally independent seniors.
When you have a staff that is very attuned to geriatric needs and they know about continuity of care and medication interactions its just an added resource to help you be a better physician and take care of patients, not only taking care of them in the emergency department but also upon discharge making sure they're all set up for follow-up care and social services. There's so much work that has gone into the physical plan. The point here is to make it much less noisy. These ceiling tiles are 4 inches thick and they have insulation above them. These lights change color to appear soothing as a patient when you're in here we can change the lights any way you want. We have incandescent lights, dimmable flourescent lights, these mattresses are dense foam mattresses and that way its more comfortable if you have to stay here for an extended period of time. The flooring is non-glare non-slip and we're going to encourage our patients while they're here if they're waiting for tests to walk up and down this hallway. Part of our healing is we have a medical harpist for people who are very anxious, if we can make them more calm we can better manage their anxiety, their blood pressure, their delirium, and we can use less medications and give better healthcare.
This coming year we'll see 28,000 seniors that will come through our geriatric emergency department. This absolutely is the way to the future, having an emergency department with staff and follow-ups you're helping to plan accordingly and also prevent a lot of repeat visits to the emergency department. Geriatrics particularly will feel very welcomed and gratified by all the special treatment they are going to receive.
Because of the flexibility of this administrative staff, the Sisters willing to try something new we were able to put together a program that never existed anywhere in the country that now will become the standard for geriatric emergency care.


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Quick Facts
- NAME: Jeff Bezos
- OCCUPATION: Entrepreneur
- BIRTH DATE: January 12, 1964 (Age: 50)
- EDUCATION: Princeton University
- PLACE OF BIRTH: Albuquerque, New Mexico
- Full Name: Jeffrey Preston Bezos
- AKA: Jeffrey Bezos
- AKA: Jeff Bezos
- ZODIAC SIGN: Capricorn
Best Known For
American entrepreneur Jeff Bezos is the founder and chief executive officer of Amazon.com. In 2013, he purchased The Washington Post.
Videos see all videos
Jeff Bezos the Trekkie (2:12)
Jeff Bezos Starts Amazon (2:37)
Jeff Bezos - Full Biography (41:17)
Steve Jobs - Mini Biography (3:39)
Jeff Bezos the Trekkie
When "Star Trek" first came out in the 1970's Jeff Bezos became an early and avid Trekkie.
Jeff Bezos Starts Amazon
After reading a study in 1994 that stated the internet was growing at a rate of 2,300% per year, Jeff Bezos decided to capitalize on that growth with his e-commerce start up Amazon.
Jeff Bezos - Full Biography
Business whiz Jeff Bezos started Amazon.com in the garage of his rented house with start-up money he borrowed from his parents.
Steve Jobs - Mini Biography
Steve Jobs met Steve Wozniak while in high school and in 1976, they started Apple Computers. Jobs oversaw the development of revolutionary products like the iPhone and iPad.
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Play NowJeffrey Preston Bezos. (2014). The Biography Channel website. Retrieved 01:39, Mar 12, 2014, from http://www.biography.com/people/jeff-bezos-9542209.
Jeffrey Preston Bezos. [Internet]. 2014. The Biography Channel website. Available from: http://www.biography.com/people/jeff-bezos-9542209 [Accessed 12 Mar 2014].
"Jeffrey Preston Bezos." 2014. The Biography Channel website. Mar 12 2014, 01:39 http://www.biography.com/people/jeff-bezos-9542209.
"Jeffrey Preston Bezos," The Biography Channel website, 2014, http://www.biography.com/people/jeff-bezos-9542209 [accessed Mar 12, 2014].
"Jeffrey Preston Bezos," The Biography Channel website, http://www.biography.com/people/jeff-bezos-9542209 (accessed Mar 12, 2014).
Jeffrey Preston Bezos [Internet]. The Biography Channel website; 2014 [cited 2014 Mar 12] Available from: http://www.biography.com/people/jeff-bezos-9542209.
Jeffrey Preston Bezos, http://www.biography.com/people/jeff-bezos-9542209 (last visited Mar 12, 2014).
Jeffrey Preston Bezos. The Biography Channel website. 2014. Available at: http://www.biography.com/people/jeff-bezos-9542209. Accessed Mar 12, 2014.
Entrepreneur and e-commerce pioneer Jeff Bezos was born on January 12, 1964, in Albuquerque, New Mexico. Bezos had an early love of computers and studied computer science and electrical engineering at Princeton University. After graduation, he worked on Wall Street, and in 1990 became the youngest senior vice president at the investment firm D.E. Shaw. Four years later, he quit his lucrative job to open Amazon.com, a virtual bookstore that became one of the internet's biggest success stories. In 2013,
"We will need to invent, which means we will need to experiment. Our touchstone will be readers, understanding what they care about—government, local leaders, restaurant openings, scout troops, businesses, charities, governors, sports—and working backwards from there. I'm excited and optimistic about the opportunity for invention."
[On the future of 'The Washington Post,' which recently came under Bezos's ownership.]
Bezos made headlines when he purchased The Washington Post in a $250 million deal.
Early Life and Career
Jeff Bezos was born on January 12, 1964, in Albuquerque, New Mexico, to a teenage mother, Jacklyn Gise Jorgensen, and his biological father, Ted Jorgensen. Bezos's parents were married less than a year, and when Bezos was four years old his mother married his step-father Mike Bezos, a Cuban immigrant.
As a child, Jeff Bezos showed an early interest in how things work, turning his parents' garage into a laboratory and rigging electrical contraptions around his house. As a teenager, his family moved to Miami where he developed a love for computers and excelled in school, becoming the valedictorian of his class. In high school, he also started his first business, the Dream Institute, an educational summer camp for fourth, fifth and sixth graders.
Bezos pursued his interest in computers at Princeton University, where he graduated summa cum laude in 1986 with a degree in computer science and electrical engineering. After graduation, he found work at several firms on Wall Street including Fitel, Bankers Trust, and the investment firm D.E. Shaw where he met his wife Mackenzie and was named the youngest vice president in 1990. While his career in finance was extremely lucrative, Bezos chose to make a risky move into the nascent world of e-commerce. He quit his job in 1994, moved to Seattle and targeted the untapped potential of the internet market by opening an online bookstore.
Pioneering E-Commerce
Bezos set up the office for his fledgling company in his garage where, along with a few employees, he began developing software. They expanded operations into a two-bedroom house, equipped with three Sun Microstations, and eventually developed a test site. After inviting 300 friends to beta test the site, Bezos opened Amazon.com, named after the meandering South American River, on July 16, 1995.
The initial success of the company was meteoric. With no press promotion, Amazon.com sold books across the United States and in 45 foreign countries within 30 days. In two months, sales reached $20,000 a week, growing faster than Bezos and his start-up team had envisioned.
Amazon.com went public in 1997 and many market analysts questioned whether the company could hold its own when traditional retailers launched their own e-commerce sites. Two years later, the start-up not only kept up, but also outpaced competitors, becoming an e-commerce leader.
Bezos continued to diversify Amazon's offerings with the sale of CDs and videos in 1998, and later clothes, electronics, toys and more through major retail partnerships.
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Facebook, Twitter, Google, iPhone— they're the names of technologies so pervasive in our 21st century lives that we've started using them as verbs. Behind these technologies are individuals whose ingenuity and enterprising spirit have profoundly changed our lives. Far from being computer nerds, these tech geniuses are billionaire celebrities, household names and the subjects of hit movies. From Steve Jobs of Apple to Mark Zuckerburg of Facebook, here are the most famous modern titans of tech.
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Magnetic Clasp Bracelet!A beautiful gift for the horse lover in your life! This silver-tone bracelet is made of horseshoes linked together. Alternating links are rhinestone encrusted or antiqued with rope-edge and metal studs.7" long Hinged magnetic clasp Customers who purchased this, also purchased these products: |
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