Scar free healing

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Scar-based healing is the process by which significant injuries can heal without permanent damage to injured tissues that have affected. In most healing, scars are formed due to fibrosis and wound contractions, but in scar-free healing tissue is completely regenerated. Repair scars, and scar-free healing is an important and relevant medical field. During the 90s, published research on the subject increased; it is a relatively new term in the literature. Free healing of scars is something that happens in the life of the fetus but the capacity lost during development into adulthood. In amphibians, tissue regeneration occurs, for example, as in skin regeneration in adult axolotl.

Video Scar free healing

Scars versus free healing scars

Scars occur in response to tissue that is damaged or lost after injury due to biological processes or injury, it is a process that occurs to replace lost tissue. The scarring process is complex, involving inflammatory and remodeling responses among other cell activities. Many growth factors and cytokines are also involved in the process, as well as the interaction of the extracellular matrix. Mast cells are one type of cell that acts to increase scarring.

Scars during healing can cause physical and psychological problems, and are a significant clinical burden which is the reason why the concept of scar-free healing is a concern. Some of the problems in scar healing lie in the physical outcome of the process: for example when collagen is abnormally arranged in scar tissue. Collagen scars are arranged in parallel bundles of collagen fibers while healthy scar-free tissue has a "weave basket" structure (Figure 1). The difference in collagen regulation along with the lack of differences in dermal tissue when healing has occurred with or without scarring is an indication of a normal skin regenerative failure. The severe scar tissue resulting from this collagen deposit is known as hypertrophic scarring and is of great concern throughout the world with events ranging from 32-72%.

Maps Scar free healing

Free healing wounds in nature

Unlike the limited regeneration seen in adult humans, many groups of animals have the ability to regenerate damaged tissue. Full leg regeneration looks good on invertebrates (eg, starfish and flatworms that can regenerate with fully functional appendages) and some vertebrates, but in the latter it is almost always confined to immature members of the species: an example is a tadpole that can regenerate its tail and various other body parts, an ability not seen in adult frogs. The exception to this is the much studied urodele species of amphibians, also known as salamanders, which bring their complete regeneration abilities to maturity. These vertebrates have a remarkable ability to allow the regeneration of all limbs and their tails (as well as many of their internal organs as well, including their spinal cord) through a process known as blastema formation. This involves closing the wound by layers of epithelial cells known as wound caps and subsequent innervation of this area with nerves that emit signals that return localized cell differentiation (such as muscle, cartilage and connective tissue) back to undifferentiated cell lines. also known as mesenchymal cells. This area is known as the blastema that has the potential to differentiate and proliferate once again so as to enable the regrowth of the leg similar to how it occurs during development. In wound healing in urodeles it is a rapid response to anti-inflammatory macrophages that have been shown to be key to their regenerative abilities. In one study, it was found that limbs would not regenerate in urodeles with depleted macrophages and would instead leave scars with permanent loss of functionality. Knowing how regeneration occurs in such animals can have major implications for how wound healing is handled in medicine and research has been directed at this area, as a result.

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Fetal vs. adult healing in humans

Reparation of tissue in a mammalian fetus is radically different from the observed healing mechanisms in healthy adults. During early pregnancy, fetal skin injuries have a remarkable ability to heal quickly and without scar formation. Wound healing itself is a very complex process and the mechanism by which scarring occurs involves inflammation, fibroplasia, granulation tissue formation and ultimately scarring. Since the observation of scar-free healing was first reported in the early fetus more than three decades ago, the study has focused on the underlying mechanisms that separate fetal injury repair without scarring from normal adult wound healing.

Scar-free healing has been documented in the fetus throughout the animal kingdom, including rats, mice, monkeys, pigs and humans. It is important to note that the ability of the fetus to heal without scarring is the size of the wound depends and also depends on age, where after a certain gestational age, usually 24 weeks in humans, the formation of a typical scar will occur. Although the exact mechanism of wound healing in the fetus is still unknown, studies show that it is thought to be due to the complex interactions of extracellular matrix components (ECM), inflammatory responses, cell mediators and specific expression. growth factor.

Intrauterine environment

Initially, it is thought that the intrauterine environment, the sterile amniotic fluid surrounding the embryo, is responsible for the healing of free fetal scarring. The reason that embryo wounds heal without a trace because they are not exposed to the same pollutant agent that normal adult sores are exposed such as bacteria and viruses. However, this theory is discredited by investigating the healing of fetal wounds in young marsupial pouches. These sacs can often be exposed to the mother's feces and urine, a very different environment to the sterile intrauterine environments seen in eutherian embryos. Despite these differences, skin lesions on marsupials heal without scar formation, proving irrelevant to the embryonic environment in scar-free healing.

Immune system cell and inflammatory response

One of the major differences between free healing scars of embryo and adult scar is the role played by the immune system cells and the inflammatory response.

Table 1 : Summary of key differences identified between fetal and adult wound healing.

The fetal immune system may be described as 'immunological immunity' because of marked decreases in neutrophils, macrophages, monocytes, lymphocytes and inflammatory mediators, as compared with adult wounds. Physiologically, adult and fetal neutrophils differ, due to the fact that neutrophil concentrations are higher in adults than fetuses, this results in wound phagocytosis and the recruitment and release of inflammatory cytokines. Leads to the promotion of a more aggressive inflammatory response in adult wound healing. It is also suspected that the time at which this inflammatory response occurs, is much shorter in the fetus thus limiting the damage.

The role of extracellular matrix and its components

Another difference between healing embryo and adult wounds is due to the role of fibroblast cells. Fibroblasts are responsible for the synthesis of ECM and collagen. In the fetus, fibroblasts can migrate at a faster rate than those found in adult wounds. Fibroblasts of the fetus may also proliferate and synthesize collagen simultaneously, compared with adult fibroblasts in which the synthesis of collagen is delayed. This delay is both in deposits of collagen and migration, which may contribute to adult scar formation.

Cell surface proteins and receptors found in ECM differ in wound healing in fetuses and adults. This is due to early regulation of cell adhesion proteins such as fibronectin and tenascin in the fetus. During early pregnancy in rabbit fetal wounds, the production of fibronectin occurs about 4 hours after injury, much faster than adult wounds where fibronectin expression does not occur until 12 hours post-wound. The same pattern can be seen in tenascin deposition. This fetal fibroblast ability to express and deposit fibronectin and tenascin rapidly, which ultimately allows cell migration and attachment to occur, produces a regular matrix with fewer scar tissue.

The other major components of ECM are hyaluronic acid (HA), glycosaminoglycans. It is known that fetal skin contains more HA than adult skin due to more HA receptor expression. HA expression is known to decrease the recruitment arrangement of inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-?); since fetal injuries contain a number of proinflammatory mediators that are less than adult wounds, it is thought that higher HA levels in fetal skin aid in healing are scar-free.

Analysis using microarray also showed that gene expression profiles differ greatly between free scar scars and postnatal lesions with scar formation. In wound healing without scarring there is a significant increase in regulation in genes associated with cell growth and proliferation, considered a major factor contributing to the rapid wound closure seen in the fetus. While wound healing in the fetus has been proven to be completely unmarked in an age-dependent way, adult mammals do not have complete healing scarring but have some regenerative properties. Adult regeneration is limited to a number of organs, especially, the liver.

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Advanced regeneration in adult humans

There are several examples of regeneration in humans that continue after the life of the fetus to adulthood. Generally, adult wound healing involves a fibrotic process that causes wound contractions that can lead to scar tissue formation. But in regeneration, the new network is fully synthesized. This can lead to a scar-free healing in which the function and organ structure is restored. However, organ regeneration is not fully understood.

Two types of regeneration in adult humans are currently recognized; spontaneous and induced.

Spontaneous regeneration occurs in the human body naturally. The best known example of this is liver regeneration, which can regenerate up to two thirds of the mass when injured by surgical removal, ischemia or after exposure to harmful toxins. (Figure 2)

Through this mechanism the heart can be restored to its original state, free of scars. However, although nearly 80 years of research on liver regeneration many debates still revolve around the exact mechanisms by which processes occur.

Another example of spontaneous regeneration of the uterine endometrium layer after menstruation during reproductive period. The endometrial gland of the uterine wall basal layer may regenerate the functional layer without fibrosis or scarring.

More recently, the kidney has been found to have the ability to regenerate. After removal or the inability of one kidney the other can double in size to fight other kidney loss. This is known as compensation growth.

Induction regeneration is stimulated by external sources of "non-regenerative" organs. In humans is for therapeutic use. Induction regeneration is currently being tested to replace organ transplants because problems such as rejection, lack of donors and scarring will be eliminated.

The table below details some of the tissues in which induction regeneration has been tried;

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Clinical burden and implications of scarring

After an injury or surgery, the doctor's primary goal is to restore full function to the patient and help ensure they return to their original state prior to trauma or skin surgery. Ensure the patient returns as close as possible to their original appearance and the original function is challenging in the context of scarring. Scar-free healing has not been observed in healthy post-gestational humans, although seen in human embryos. Currently, it is only possible to reduce visibility of scars, and NHS suggests a number of different methods for doing this including corticosteroid injections, skin creams, silicone gel, pressure dressings, dermal fillers, radiotherapy and laser therapy. Although this method can reduce the appearance of scars, but does not produce scar-free display. Billions of pounds are used for wound care and healing on the NHS every year. Between 2014 and 2015 in England and Wales, 19,239 people suffered burns requiring hospitalization. In addition to significant financial costs, the cost of scarring is also very great for patients. One study of the quality of life of patients with scars found that more than half the participants felt stigmatized by their scars and felt their personal relationships deteriorate. In addition to this, 68% try to hide their scars, while reporting their working life, confidence and the ability to communicate with others have been negatively affected. Future research and progress in free-wound healing can reduce costs for the NHS while also improving the quality of life for many affected people.