Clotting also helps to close and heal the wound, making a scab. First, the blood vessels around the wound open a bit to allow more blood flow to it. Fresh blood brings more oxygen and nutrients to the wound. White blood cells called macrophages help clean the wound by fighting any infection. They also send out chemical messengers called growth factors that help repair the area. Phase 3: Rebuilding After the wound is clean and stable, your body can begin rebuilding the site.
Oxygen-rich red blood cells come to the site to create new tissue. Chemical signals in the body tell cells around the wound to make elastic tissues called collagen. Deep wounds that damage the dermis, or even the underlying muscle and fat, are more difficult to heal than shallow, epidermal-only wounds. The wound healing processes may be extended and scar tissue is likely to form due to improper re-epithelialization.
Additionally, deep wounds are more susceptible to infection, and also to the development of systemic infection through the circulatory system, as well as dysregulation that results in chronic wounds such as ulcers. Wound healing phases : This image illustrates the phases of wound healing. Limits vary within faded intervals, mainly by wound size and healing conditions, but the image does not include major impairments that cause chronic wounds.
The wound healing process for deep wounds is similar to that of shallow wounds. However, with the removal of the dermis and its associated skin appendages, re-epithelialization can only occur from the wound edge, with no contribution from the dermal compartment. Therefore, proper reconstitution of the epidermis is often only seen at the edge of the wound, with fibrous scar tissue—formed from the extracellular matrix ECM deposited during the proliferative phase—covering the rest of the wound site.
With the formation of a scar, the original physiological properties of the tissue are lost. For example scars are less flexible than skin, and do not feature sweat glands or hair follicles. The ECM formed during wound healing may also be weaker in deep wounds, making the site susceptible to additional later wounding.
The provisional ECM laid down during the proliferative phase is rich in fibronectin and collagen III that combine to allow quicker cell movement through the wound, which is very important during wound healing. However, the ECM of mature skin is rich in collagen I.
Privacy Policy. Skip to main content. Integumentary System. Search for:. Wound Healing. Steps of Tissue Repair Wound healing is divided into four overlapping states: 1 homeostasis, 2 inflammatory, 3 proliferative, and 4 remodeling. Learning Objectives Describe the overlapping phases of tissue repair. Key Takeaways Key Points Wound healing is the process whereby the skin repairs itself after injury. Wound healing can be divided into four overlapping processes; maintenance of homoeostasis, an inflammatory response, a proliferative phase, and remodeling.
Maintenance of homoeostasis is achieved by clotting in any damaged regions of the circulatory system. The inflammatory response clears the wound site of debris and prevents infection.
During the proliferative phase new tissue and an extra cellular matrix to support tissue repair are laid down. It has been proved that one of the factors which affect SRF activity is the dynamics of cytoskeleton and the activity of cofactor G-actin MAL Megakaryoblastic Leukaemia 1 [ 98 ].
The monomeric actin G-actin while binding with MAL closes proteins pathway to the nucleus and its functional inhibition. As a result of serum stimulation and Rho activation, the polymerization of actin increases and the level of actin monomers decreases.
In such conditions, MAL is released to the nucleus where it starts the transcription of independent genes. The factors which induce polymerization of F-actin decrease the pool of free G-actin and, at the same time, they increase the availability of MAL, which may lead to SRF activation [ 99 ].
The model of in vitro differentiation of epidermal stem cells by mechanotransduction, with the use of microsamples of matrix islands, showed that cells growing on the larger islands form a dense network of actin filaments and stress fibers thereby reduce the pool of free G-actin and increase the availability of MAL.
SRF activation through mechanical signals is an alternative or parallel way to the activity of growth factors on epidermal cells [ 23 ]. In further studies, it was described as a protein which is bound to SKP1, with which it composes a ligase ubiquitin type SCF complex Skp1-cullin-F-box that takes part in the regulation of cell cycle through proteolysis dependent on ubiquitin.
Ubiquitination and the proteasome degradation of p27 enable the transition S-phase cell cycle and promote cell proliferation [ ]. SKP2 expression and the promotion of proliferation are the result of cooperation between the signalization of growth factors and mechanical forces which affect a cell.
In the studies carried out on smooth muscles and fibroblasts, it was shown that the growth factors regulate the level of SKP2 on the level of protein stabilization; in contrast, the increase of mechanical tension of cells causes the increase of protein expression on the level of transcription. Cell adhesion to substrate and mechanical tension of cells is conditional to maintain the transcription of SKP2 [ ].
NFAT1 belongs to a family of four transcription factors which are activated by the level of calcium ions in the cytoplasm. Calcium ions, through the mechanism dependent on calmodulin, activate the phosphatase of calcineurin.
A full dephosphorylation of NFAT1 leads to conformational shifts, which activates such protein functions as translocation to the nucleus, binding with the DNA and activation of transcription [ ]. The transcription factor NFAT1 is activated in response to the increase of mechanical tension of a cell, which leads to the increase of expression of SKP2 protein. Conformational shifts of NFTA1, as a result of dephosphorylation, are tightly related to cells adhesion and the formation of mechanical forces dependent on the cell adhesion surface.
This point supports the studies which show that the level of mRNA SKP2 in adherent cells may be regulated by the change in their shape. Results of many studies point that Skp2 is regulated by the influence of mechanical forces onto a cell. Shifts in mechanical tension of cells regulate mRNA level in bladder and vascular smooth muscle cells and skin fibroblasts.
This leads to the assumption that the regulation of SKP2 transcription through actions of mechanical forces is an element of many, if not all, physiological and pathological processes dependent on the regulation of intensification of cell divisions, such as morphogenesis, tissues regeneration, and wound healing [ ].
Basic research of cell and tissue mechanobiology and clinical studies point to the importance of mechanical forces in the process of skin regeneration and wound healing. More important questions to be answered is how these molecules in specific pathways interact with each other in response to mechanical force and what controls target gene activity and what mechanosensing perturbed in skin regenerations and wound healing.
The outcome of these studies is the development of new therapies which use mechanical forces that support proper healing. It may be observed that the development of therapies based on the use of mechanical forces, or of bandages with appropriate mechanical properties, prevents improper scarring.
The importance of mechanical signaling in scars formation points to the observation associated with the use of botulinum toxin type A in aesthetic medicine used to treat local subcutaneous muscle paralysis. The observations noted decrease of scarring in the areas where botulinum toxin was used; these effects are attributed to the reduced wound tension during its remodeling.
Early clinical studies also show that injection of botulinum toxin into the wound site reduces the formation of hypertrophic scars [ ]. Wounds auxiliary therapy treatment which uses devices that generate negative pressure NPWT—negative pressure vacuum-assisted closure technology is an effective method that supports extensive and rapid healing of chronic wounds.
Functioning of NPWT facilitates the approximation of wound edges and stabilizes the environment, which reduces edema and ascites, and also reduces micromechanical forces [ ]. Another beneficial therapy, which is deemed as effective physical modality for soft tissue wounds and which probably induces mechanisms of mechanotransduction and immunomodulation, is high-energy acoustic waves ESWT—extracorporeal shock wave therapy [ ].
Results of the current studies suggest there is strong evidence documenting that ESWT application is safe and effective for the treatment of different etiologically soft tissue wounds, both acute and chronic. Clinical efficiency of ESWT shows a wide range of positive results, such as completed wound closure and reepithelialization, enhanced tissue granulation, reduced necrotic fibrin tissue, improved blood flow perfusion and angiogenesis, reduced period of total wound treatment, and decreased necessity of antibiotic treatment [ ].
It seems that the mechanism of NPWT or ESWT, functioning as a technique for supporting wound healing, is based on mechanotransduction, and further researches are focused on the assessment of the optimal therapeutic parameters and the use of additional materials supporting therapy. The results of the studies and the opinions of clinicians show the importance of the transduction of mechanical forces in the process of wound healing and scar formation.
The growing importance of mechanotransduction in wound healing and scar formation will contribute, to a large measure, to designing, to new clinical therapies, and to surgical procedures. A better understanding of mechanobiology will enable the design of biomaterials, with appropriate physical and chemical properties, which will be used to treat improperly healing wounds. In addition, it will allow developing devices which will precisely control the mechanics of the wound and individualizing the therapy depending on the type, size, and anatomical location of the wound in certain patients, which will increase the efficiency of clinical therapy.
Linking mechanobiology with the science of biomaterials and nanotechnology will enable in the near future a precise interference in abnormal cell signaling responsible for the proliferation, differentiation and cell death, and the restoration of biological balance. In addition, knowledge of the mechanisms of mechanical signal transduction and its involvement in the activation of certain genes opens up new ways for combination therapies that use mechanical and drug therapy.
This can increase the effectiveness of treatment. National Center for Biotechnology Information , U. Journal List Biomed Res Int v.
Biomed Res Int. Published online Jun Author information Article notes Copyright and License information Disclaimer. Received Feb 24; Accepted Apr This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This article has been cited by other articles in PMC. Abstract Basic and clinical studies on mechanobiology of cells and tissues point to the importance of mechanical forces in the process of skin regeneration and wound healing.
Introduction Skin is a multifaceted biological system which integrates different cells in the area of a tightly organized extracellular matrix.
Mechanical Regulated Cell Proliferation and Differentiation A widely accepted concept of homeostasis describes that structural damage to tissues activates the response of the organism to restore impaired mechanical equilibrium of the skin. Transcription Factors Regulated by Mechanical Forces 3. Open in a separate window. Figure 1. YAP and TAZ in Skin Homeostasis and Wound Healing The process of stratification of the epidermis can be interpreted as cell differentiation induced by the loss of cell-extracellular matrix contact.
Development Prospects and Clinical Implications Basic research of cell and tissue mechanobiology and clinical studies point to the importance of mechanical forces in the process of skin regeneration and wound healing. Competing Interests The authors declare that they have no competing interests. References 1. Gurtner G. Wound repair and regeneration. Zielins E. Wound healing: an update.
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