Katana VentraIP

Wound healing

Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue.[1]

In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier against the external environment. When the barrier is broken, a regulated sequence of biochemical events is set into motion to repair the damage.[1][2] This process is divided into predictable phases: blood clotting (hemostasis), inflammation, tissue growth (cell proliferation), and tissue remodeling (maturation and cell differentiation). Blood clotting may be considered to be part of the inflammation stage instead of a separate stage.[3]


The wound-healing process is not only complex but fragile, and it is susceptible to interruption or failure leading to the formation of non-healing chronic wounds. Factors that contribute to non-healing chronic wounds are diabetes, venous or arterial disease, infection, and metabolic deficiencies of old age.[4]


Wound care encourages and speeds wound healing via cleaning and protection from reinjury or infection. Depending on each patient's needs, it can range from the simplest first aid to entire nursing specialties such as wound, ostomy, and continence nursing and burn center care.

Hemostasis (blood clotting): Within the first few minutes of injury, in the blood begin to stick to the injured site. They change into an amorphous shape, more suitable for clotting, and they release chemical signals to promote clotting. This results in the activation of fibrin, which forms a mesh and acts as "glue" to bind platelets to each other. This makes a clot that serves to plug the break in the blood vessel, slowing/preventing further bleeding.[5][6]

platelets

Inflammation: During this phase, damaged and dead cells are cleared out, along with bacteria and other pathogens or debris. This happens through the process of , where white blood cells engulf debris and destroy it. Platelet-derived growth factors are released into the wound that cause the migration and division of cells during the proliferative phase.

phagocytosis

Proliferation (growth of new tissue): In this phase, , collagen deposition, granulation tissue formation, epithelialization, and wound contraction occur.[7] In angiogenesis, vascular endothelial cells form new blood vessels.[8] In fibroplasia and granulation tissue formation, fibroblasts grow and form a new, provisional extracellular matrix (ECM) by excreting collagen and fibronectin.[7] Concurrently, re-epithelialization of the epidermis occurs, in which epithelial cells proliferate and 'crawl' atop the wound bed, providing cover for the new tissue.[9] In wound contraction, myofibroblasts decrease the size of the wound by gripping the wound edges and contracting using a mechanism that resembles that in smooth muscle cells. When the cells' roles are close to complete, unneeded cells undergo apoptosis.[7]

angiogenesis

Maturation (remodeling): During maturation and remodeling, collagen is realigned along tension lines, and cells that are no longer needed are removed by programmed cell death, or .

apoptosis

Timing and re-epithelialization[edit]

Timing is important to wound healing. Critically, the timing of wound re-epithelialization can decide the outcome of the healing.[11] If the epithelization of tissue over a denuded area is slow, a scar will form over many weeks, or months;[12][13] If the epithelization of a wounded area is fast, the healing will result in regeneration.[13]

Maturation and remodeling[edit]

When the levels of collagen production and degradation equalize, the maturation phase of tissue repair is said to have begun.[20] During maturation, type III collagen, which is prevalent during proliferation, is replaced by type I collagen.[17] Originally disorganized collagen fibers are rearranged, cross-linked, and aligned along tension lines.[31] 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,[28] ranging from approximately three days[41] to three weeks.[56] The maturation phase can last for a year or longer, similarly depending on wound type.[28]


As the phase progresses, the tensile strength of the wound increases.[28] Collagen will reach approximately 20% of its tensile strength after three weeks, increasing to 80% after 12 months. The maximum scar strength is 80% of that of unwounded skin.[57] 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.[20]


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[7] such as a venous ulcer or pathological scarring such as a keloid scar.[58][59]

Moisture; keeping a wound moist rather than dry makes wound healing more rapid and with less pain and less scarring

[60]

Mechanical factors

Oedema

Ionizing radiation

Faulty technique of wound closure

and necrosis

Ischemia

Foreign bodies. Sharp, small foreign bodies can penetrate the skin leaving little surface wound but causing internal injury and internal bleeding. For a glass foreign body, "frequently, an innocent skin wound disguises the extensive nature of the injuries beneath". First-degree nerve injury requires a few hours to a few weeks to recover.[62] If a foreign body passes by a nerve and causes first-degree nerve injury during entry, then the sensation of the foreign body or pain due to internal wounding may be delayed by a few hours to a few weeks after entry. A sudden increase in pain during the first few weeks of wound healing could be a sign of a recovered nerve reporting internal injuries rather than a newly developed infection.

[61]

Low

oxygen tension

Perfusion

Provide wound protection

Remove excess

exudate

Possess properties

antimicrobial

Maintain a humid environment

Have high permeability to oxygen

Are easily removed from a wound site

Possess non- characteristics

anaphylactic

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.[96] 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.[97] 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.[98]


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).[99] Relationships like these can be incorporated into an agent-based models, where the sensitivity to single parameters such as initial collagen alignment, cytokine properties, and cell proliferation rates can be tested.[100]

Examples of primary intention include: well-repaired , well reduced bone fractures, healing after flap surgery.

lacerations

Early removal of dressings from clean or clean-contaminated wounds does affect primary healing of wounds.

[103]

Biologics, skin substitutes, biomembranes and scaffolds[edit]

Advancements in the clinical understanding of wounds and their pathophysiology have commanded significant biomedical innovations in the treatment of acute, chronic, and other types of wounds. Many biologics, skin substitutes, biomembranes and scaffolds have been developed to facilitate wound healing through various mechanisms.[108] This includes a number of products under the trade names such as Epicel, Laserskin, Transcyte, Dermagraft, AlloDerm/Strattice, Biobrane, Integra, Apligraf, OrCel, GraftJacket and PermaDerm.[109]