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The Science of Wound Healing
(excerpt from an article by Kathy Dix)

Virginia Rybski, a molecular biologist, is vice president of corporation development for Regenesis Biomedical. The science of wound healing, she observes, still has room for improvement. “There are three distinct sequential phases of wound healing: inflammatory phase, proliferative phase, and maturational phase. The inflammatory phase is characterized by inflammation and hemostasis. When the injury occurs to the skin, the cell membranes release vasoconstrictor proteins to help limit immediate hemorrhage, then the capillaries dilate to allow inflammatory cells to migrate to the wound. Platelets are the first cells to respond to a wound site. They release chemokines to help with clot formation. Next, neutrophils are attracted to the wound site when the complement cascade is activated by platelet degranulation. Neutrophils help kill bacteria and remove foreign debris from the wound. Later, leukocytes and macrophages respond to the wound site. Macrophages produce and secrete numerous types of proteins. These include collagenases that debride the wound, interleukins and tumor necrosis factor (TNF) that stimulate fibroblasts (produce collagen) and promote angiogenesis, and transforming growth factor (TGF) that stimulates keratinocytes. This step marks the transition into the proliferative phase.

“The proliferative phase includes epithelialization, angiogenesis, granulation tissue formation, and collagen deposition. Epithelialization — the regrowth of the epidermis — occurs early in wound repair. If the basement membrane remains intact between the epidermis and the dermis, the epithelial cells migrate upwards in the normal pattern to heal the wound. The epithelial progenitor cells remain intact below the wound and the normal layers of epidermis are restored in two to three days. If the basement membrane has been destroyed, similar to a second- or third-degree burn, then the wound is re-epithelialized from the normal cells in the periphery and from the skin appendages. Angiogenesis, stimulated by the protein TNF-alpha, is marked by endothelial cell migration and capillary formation. The new capillaries deliver nutrients to the wound and help maintain the granulation tissue bed. The migration of capillaries into the wound bed is critical for proper wound healing. The granulation phase and tissue deposition require nutrients supplied by the capillaries, and failure for this to occur results in a chronically unhealed wound. The final part of the proliferative phase is granulation tissue formation. Fibroblasts differentiate and produce ground substance and then collagen. The ground substance is deposited into the wound bed; collagen is then deposited as the wound undergoes the final phase of repair.

“The final phase of wound healing is the maturational phase. The wound undergoes contraction, ultimately resulting in a smaller amount of apparent scar tissue. The entire process is a dynamic continuum with an overlap of each phase and continued remodeling. The wound reaches maximal strength at one year, with a tensile strength that is 80 percent of normal skin. Collagen deposition continues for a prolonged period, but the net increase in collagen deposition plateaus after 21 days.”

Chronic wounds are wounds that do not heal within the first 30 days — unlike acute wounds — and do not respond to standard wound care practices. “Some researchers believe that all chronic wounds are infected,” Rybski says.

“There are numerous advanced treatment methods for chronic, non-healing wounds. These can be segmented into three main categories: pharmaceutical agents, wound dressings, and medical devices. Pharmaceutical agents include antibiotics; however, a recent systematic review of antimicrobial agents has concluded that systemic or topical antimicrobials are not generally indicated for the management of chronic wound infections. However, there may be some value in the prophylactic use of topical antimicrobials for the initial management of acute cellulitis. There is also a pharmaceutical agent containing platelet-derived growth factor (PDGF) called Regranex®, by Johnson & Johnson, which helps wounds granulate, as well as various agents to enzymatically debride wounds, such as Accuzme by Healthpoint, and ointments that contain trypsin, Balsam Peru, and Castor Oil that act as enzyme debriders, epithelial agents and pain reducers, such as Meander® by Healthpoint.”

“There are a wide variety of wound dressings that are used for various types of wounds,” Rybski continues. “Amorphous hydrogels vary in thickness and viscosity and may help facilitate autolytic debridement of necrotic tissue. Care must be taken not to apply hydrogels to periwound skin as they may cause maceration. Hydrogel dressings contain up to 95 percent water and thus cannot absorb much exudates, so they are used in dry wounds such as pressure ulcers, skin tears, surgical wounds, and radiation burns. Hydrocolloid dressings are occlusive and do not allow water, oxygen, or bacteria into the wound. This may help angiogenesis and granulation and even lower the pH of the wound bed to prevent bacterial growth, but they should not be used in the wound in infected. Alginate dressings absorb moderate-to-high amounts of wound drainage and may be used in infected and non-infected draining-type wounds. The alginate forms a gel when it comes in contact with fluid and may absorb up to 20 times its weight in fluid. As such they should not be used in dry wounds. Composite dressings — containing multiple layers — may be used in wounds with minimal to heavy exudates, healthy granulation tissue, and necrotic tissue; however, they should not be used if the patient has frail or dehydrated skin. Transparent films are flexible sheets of polyurethane coated with an adhesive so that the caregiver can easily monitor the wound bed through the film, however they should not be used in areas where there is a high friction level, such as with the buttocks or sacrum. Films also are semi-occlusive and trap moisture, creating a moist wound environment. Silver dressings have become available, since silver interferes with bacterial electron transport system and inhibits the multiplication of the bacteria. However, to achieve this, silver ions have to be able to enter a cell, so the chemical bonding of silver with a sulphonamide antimicrobial — sulphadiazine — has resulted in the development of a safe broad-spectrum agent for topical use. In this formulation, silver is released slowly from the transport medium in concentrations that are selectively toxic to microorganisms such as bacteria and fungi. This type of silver product has been used successfully in the management of acute and chronic wounds. Products that can sustain the interaction of silver with microorganisms in the exuding wound are likely to be more effective in preventing/controlling local infection as potentially more silver ions will be available to enter bacterial cells. This assumes that the concentration of silver in the solution is both correct and maintained.”

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