Wound healing is divided into four overlapping states: 1 homeostasis, 2 inflammatory, 3 proliferative, and 4 remodeling. Wound healing is the process by which the skin, or any injured organ, repairs itself after injury. The main aim of wound healing is to prevent or limit further damage, to clean and seal the wound against infection, to restore tissue strength, and, if possible, tissue function.
Wounds in the skin can either be classed as epidermal shallow, in which the dermis remains intact or deep in which the dermis is damaged; this is sometimes referred to as a full thickness wound. Critical developments that occur during a localized inflammatory response : The phases of wound healing during an inflammatory response to infection.
Limits vary within faded intervals, mainly by wound size and healing conditions. The image does not include major impairments that cause chronic wounds. Upon wounding, the first phase of the wound response is concerned with maintaining homoeostasis within the body.
Most wounds, even superficial shallow wounds, result in damage to the circulatory system. To prevent blood loss and reduce the chance of infection spreading throughout the body, circulation platelets within the blood begin to form a fibrin clot, which seals the wound site. Additionally, vasoconstriction initially occurs around the wound site as a means of isolating the wound site.
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Skip to content Main Navigation Search. Dictionary Articles Tutorials Biology Forum. Wound healing is slower in the elderly, accompanied by a higher frequency of infection as the capacity of the immune system to fend off pathogen declines.
Aging is also apparent at the cellular level because all cells experience changes with aging. Telomeres, regions of the chromosomes necessary for cell division, shorten each time cells divide. As they do, cells are less able to divide and regenerate.
Because of alterations in cell membranes, transport of oxygen and nutrients into the cell and removal of carbon dioxide and waste products from the cell are not as efficient in the elderly. Cells may begin to function abnormally, which may lead to diseases associated with aging, including arthritis, memory issues, and some cancers.
The progressive impact of aging on the body varies considerably among individuals, but Studies indicate, however, that exercise and healthy lifestyle choices can slow down the deterioration of the body that comes with old age.
Figure 2. Development of Cancer. Note the change in cell size, nucleus size, and organization in the tissue. Cancer is a generic term for many diseases in which cells escape regulatory signals. Uncontrolled growth, invasion into adjacent tissues, and colonization of other organs, if not treated early enough, are its hallmarks. A mutation is defined as a permanent change in the DNA of a cell. Epigenetic modifications, changes that do not affect the code of the DNA but alter how the DNA is decoded, are also known to generate abnormal cells.
Alterations in the genetic material may be caused by environmental agents, infectious agents, or errors in the replication of DNA that accumulate with age. As changes in cells accumulate, they lose their ability to form regular tissues.
A tumor, a mass of cells displaying abnormal architecture, forms in the tissue. Many tumors are benign, meaning they do not metastasize nor cause disease. A tumor becomes malignant, or cancerous, when it breaches the confines of its tissue, promotes angiogenesis, attracts the growth of capillaries, and metastasizes to other organs Figure 2. The specific names of cancers reflect the tissue of origin.
Cancers derived from epithelial cells are referred to as carcinomas. Cancer in myeloid tissue or blood cells form myelomas. Leukemias are cancers of white blood cells, whereas sarcomas derive from connective tissue. Cells in tumors differ both in structure and function. Some cells, called cancer stem cells, appear to be a subtype of cell responsible for uncontrolled growth. The first, enzymatic and mechanical debridement the technique preferred by the authors , is the crucial moment in wound management, eliminating the mechanical and biochemical causes that can perpetuate the inflammatory process and preparing the wound for the action of biological and physical substances that can trigger a local anti-inflammatory action and catalyze the proliferation of cell populations, ensuring good hydration in the wound bed.
The lesions are always treated with the local application of medical devices, biophysical therapies and cell therapies. Administration of a dietary supplement containing a well-balanced mix of serratio-peptidase, escin, bromelain and selenium.
This supplement has proteolytic, fibrinolytic, anti-edema and draining properties, as well as an antioxidant action. The rationale for the prescription of this supplement is: Anti-inflammatory action proteolytic and fibrinolytic ;. Bacteriostatic action in uninfected lesions and antibiotic therapy in infected lesions;. Patients are prescribed with 3—6 months of treatment with low-dose cytokines, formulated with a kinetic system called Sequential Kinetic Activation SKA , and containing: Anti IL-1 - regulation and suppression of the inflammatory response.
IL - adjustment of the anti-inflammatory process in chronic diseases with reduction of IL Low dose therapy is an important part of wound management because it introduces into clinical practice a strategic concept for future therapies: the disease may be the result of an altered concentration of messenger or signal molecules hormones, cytokines, neurotransmitters for cellular activity, and in this case the modulation of these molecules can restore the disrupted balances, enabling healing [ 8 ].
During the process the wound is subjected to dual-type light frequencies for 8—20 minutes. Polarized light. RMC is the first center in Italy to use a unique light source that is: Polarized, propagating in parallel planes;. Low-energy, reaching the wound with a constant intensity, producing bio-stimulating effects.
The LumiHeal Protocol has been applied over the last 3 months in 8 patients with complicated treatment-resistant infected wounds. The improvement in the wounds is documented by photographic evidence [ 15 , 16 , 17 , 18 , 19 , 20 ]. Pulsed electromagnetic fields PEMF. High intensity, variable frequency magnetic fields for outpatient and home treatment. Are angiogenic, with increased proliferation of endothelial cells and FGF-2 fibroblast growth factor , improving microcirculation;.
Improve the microcirculation , with increased collagen production [ 21 , 22 ]. PRP is a powerful concentrate of growth factors that stimulate tissue regeneration and is used to treat damaged tissues. A old-patient with vascular ulcers of the lower limbs treated with PRP. Method for obtaining, through adipose liposuction, micro-fractured tissue for autologous use, which is reapplied to patients with skin lesions to further stimulate the cell regeneration process [ 27 , 28 , 29 , 30 ].
At the RMC, surgical therapies for the repair of skin lesions are standardized. They involve the use of skin substitutes that promote the production of a structured collagen matrix, enabling better angiogenesis. The results of their use in a treatment pathway that accompanies patients in their management are remarkable. The Prometheus Project - Alfakjn Wound Care has been embraced by the RMC because it is innovative and because it anticipates the next frontier for regenerative medicine: specific, individualized cell therapies.
Growth factors have made an explosive breakthrough into clinical practice, and the decision to focus on the quality and efficacy of the therapies containing them is strategic for the near future. To do this, we first tried to answer a question: Do difficult wounds exist, or is it simply that we do not know how to treat them?
Our research is based on two articles, published in Zhao R et al. These articles affirm what we wrote in the introduction: inflammation has a major role in the wound healing process, in which disabling chronic diseases add to local systemic effects such as tissue hypoxia and pH changes, post-revascularization damage, cell aging and infections. Therapeutic resources take account of the numerous techniques and resources available, with particular attention to growth factors.
In this research process we began with a definition: Repair 1. Repair 2. From this perspective, the RMC investigated a sterile gauze dressing in which the role of the bioactive substances hyaluronic acid, carnosine is specifically defined in the literature, and involves mechanical protection of the lesion gauze combined with a direct anti-inflammatory action.
Zhao et al. In this context, we began working with bioactive substances with innovative properties in relation to both composition and biological action in comparison with their competitors. This potential innovation lies in the use of bovine colostrum, that, when stabilized through industrial processes to a pH of 6.
This has positive consequences for the modulation of the inflammatory process and the tissue repair process as well as on the ability to stimulate the cellular and ultrastructural regenerative process. Bagnara G: Le cellule staminali , Cap Ed Esculapio The purpose of this test is to compare the efficacy of two medical devices in the repairing of wounds simulating this situation in vitro by making a cut on cell monolayer of human fibroblasts Hude and then evaluating the approximation of the edges of the cut in cells treated with the two medical devices, in comparison to untreated cells.
In order to select the concentrations of 2 medical devices to be used for the test r not cytotoxic concentrations for the cells , a preliminary MTT cell cultures of fibroblasts was performed. Based on the obtained results concentrations of 2 medical devices of 1—0. After making a cut on the cell monolayer of confluent fibroblasts simulation of a wound , the cells were treated with the chosen concentrations of the two medical devices, as negative control untreated cells were used and, as internal quality control one standard with known activity of wound healing activity.
Therefore, we have performed a morphologic evaluation of the monolayer by microscopy and a measurement of IL-8 levels. From the morphological evaluation a net approach of the flaps of the monolayer was observed in the plates treated with the various concentrations of Colostrum Gel. These results indicate that the effectiveness of the active ingredients present in the product have a different target than the reduction of the inflammatory response. The obtained results have showed the effectiveness in wound healing of the medical device Colostrum Gel, compared to the medical device Gel no active.
Colostrum Gel reduced IL8 production by fibroblasts and contains active ingredients. Those stimulate wound healing simulation in vitro by cutting the monolayer of cultured fibroblasts and evidence of the approximation of the edges of the cut and almost total closure of the same Figure 7.
Via A. Panizzi,10 Milano Italy. In vitro comparative evaluation of wound healing activity of medical devices - Cell Growth. This study reports the development of a murine model of pressure ulcers by using externally placed magnets to create the ischemic events of ischemia reperfusion IR injury.
The animals were individually housed, their backs have been shaved, cleaned with alcohol, the skin has been gently pulled up and placed between two round ceramic magnetic plates which have a mm diameter mm 2 and are 5 mm thick, with an average weight of 2.
Then the animals have been divided into two groups as follows:. Control group: three IR cycles have been performed in 3 mice to initiate decubitus ulcer formation.
A single IR cycle consists of a hour period of magnet placement, followed by a release of rest period of 12 hours. After the 3 IR cycles, the animals have been sacrificed.
Group B: three IR cycles have been performed in each mouse to initiate decubitus ulcer formation. The samples were then observed with an optical microscope Nikon 80i, fitted with a digital camera Picture 9. Initiate decubitus ulcer formation in mice to test colostrum derivative therapy.
Control group: 3 IR cycles Skin macroscopic analysis Macroscopic analysis of dorsal skin revealed the presence of mild skin lesions, edema and signs of necrosis of the epidermis.
Photo Histological analysis of dorsal skin samples stained by hematoxylin—eosin showed: wide ulcerative area of the epidermis; marked spongiosis of basal layer intercellular bridges appear very prominent ; marked diffuse inflammatory infiltrate; conjunctival edema; vascular hyperemia; presence of extravasal erythrocytes Picture Skin macroscopic analysis.
Macroscopic analysis of dorsal skin revealed: skin ulcers with necrosis areas and edema Picture Histological analysis of dorsal skin samples stained by hematoxylin—eosin showed: wide ulcerative area of the epidermis; when present epidermis is hyperplasic, with not regular thickness, marked spongiosis of basal layer and presence of lymphocytes; marked diffuse inflammatory infiltrate; conjunctival edema; vascular hyperemia; presence of extravasal erythrocytes Picture Wide ulcerative area of the epidermis; marked spongiosis of basal layer intercellular bridges appear very prominent ; marked diffuse inflammatory infiltrate; conjunctival edema; vascular hyperemia; presence of extravasal erythrocytes.
Macroscopic analysis of dorsal skin revealed: skin ulcers with necrosis areas and edema. Wide ulcerative area of the epidermis; when present epidermis is hyperplasic, with not regular thickness, marked spongiosis of basal layer and presence of lymphocytes; marked diffuse inflammatory infiltrate; conjunctival edema; vascular hyperemia; presence of extravasal erythrocytes. The most significant aspect with a view to new tissue regeneration therapies and hence the control of the inflammatory process were the results in relation to the disappearance of the wound and the reduction of the inflammatory process.
This requires the future consideration of the action time of the medical device and its contact time with the damaged tissue. The results in relation to clinical healing take account of chronic conditions defined as non-responders and their good management from the time of diagnosis. The RMC treats patients with chronic wounds of various etiologies.
In this article, the authors lay down the scientific basis for a chronic wound healing process involving an appropriate sequence of the modulation of the inflammatory and proliferative processes and remodeling of the ECM.
At the same time, they highlight how the abnormal evolution of the inflammatory process to a chronic condition involves abnormal cellularity, inappropriate collagen deposit and the presence of protease, preventing re-epithelialization and regeneration of the lesion. Picture A year-old patient with heart failure and lower limb ulcers. Knowledge of the biological pathways at an ultramolecular and cellular level enables the identification of various areas where clinical research could intervene with biological drugs or biophysical therapies to influence the healing pathways of non-responding chronic wounds or stimulate the metabolic or regenerative processes, blocking the mechanisms leading to chronicity and, in particular, intervening in the chronic inflammatory process.
In this case, in vitro tests could help by enabling new biological compounds to be tested on cellular models of skin damage. We have demonstrated that colostrum is paradigmatic of the therapeutic philosophy adopted by the RMC, in the sense that it is capable of reducing levels of proinflammatory cytokines and protease MMP-9 , blocking M1 activity and stimulating the activity of fibroblasts, resulting in the production of type III and VII collagen to aid regeneration.
Analysis of the results obtained with low dose therapy and the effects of biophysical therapies photobiomodulation and PEMF could provide guidance on aspects that the authors consider to be of current and future interest: modulation of nitric oxide in vasodilation and the provision of regenerative molecules PEMF , and the reduction of the inflammatory component IL-6 and C-reactive protein. Analysis of the current literature suggests that reduction of the inflammatory component is the key to regenerative recovery of chronic nonresponding wounds, now that we have a better understating of their pathogenesis and pathophysiological processes.
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