Skin is the largest organ in the body with many essential functions. Due to its direct contact with the external environment, it is extremely prone to damage and injury. The skin has a critical role in the human body as a barrier against pathogens, noxious substances and mechanical stress.
Presently 6.5 million patients in the United States suffer from a chronic wound. It is estimated that 1-2% of the population in developed countries will suffer from a chronic wound in their lifetimes. The current cost of chronic wound care treatment in the US is $25 billion annually.
Chronic wounds are wounds that have failed to progress through a normal sequence of repair, meaning that the wound does not have normal anatomic or functional results. There is no clear consensus on the time that defines a chronic wound, but usually the accepted range is 4 weeks to 3 months duration.
When wound healing is impaired there is usually not a single factor as the cause but multiple. Common factors associated with chronic wounds are:
- Metabolic conditions
Bacteria produce inflammatory mediators that inhibit normal wound healing. These cause prolonged inflammation and lead to cell death and necrosis. The necrotic tissue prevents new growth and acts as a culture for increased bacterial population.
Arterial insufficiency of large and medium sized vessels. The lack of blood supply in tissue leads to a decrease or absence of oxygen and tissue death. This is common in conditions associated with atherosclerosis.
Venous insufficiency due to venous hypertension or chronic deep vein thrombosis (clots.) Pressure builds causing hydrostatic gradient between veins and small arterioles, blood slows and the capillaries leak causing chronic inflammation. The reduction of nutrients and oxygen to the area causes necrotic tissue.
Pressure Injuries are caused by a combination of pressure and force. Pressure greater than arterial pressure can block nutrients and oxygen to the tissues. Tissue hypoxia leads to tissue death and necrosis. This is common over bony prominence where higher pressures are significant. Tissues most susceptible to pressure are the muscles, followed by fat and then skin. Therefore, pressure can cause significant damage well before it is discovered visually.
Diabetes is the most common metabolic condition causing chronic wounds. It affects the small vessels causing blockage and subsequent lack of oxygen to the tissues called microvascular disease. Diabetes also causes damage to the sensory and motor nerve function. Sensory dysfunction causing lack of normal sensation and pressure on normal tissue or injury is not realized. Motor function causing imbalance of normal function of the small muscles of the foot and therefore improper gait and weight distribution causing callous formation and ultimately skin breakdown.
Immunosuppressive agents inhibits the expression of several inflammatory mediator. A common agent, corticosteroid, interferes with all the major steps in the wound healing process.
Radiation used in the treatment of certain cancers sometimes can cause non healing chronic wounds. The radiation causes free radicals which can cause cellular breakdown leading to necrosis of tissue. Radiation can also cause microvascular thrombosis leaving surrounding tissues ischemic leading to necrosis.
Three Phases of Wound Healing
- Inflammatory Phase
- Proliferation Phase
- Maturation Phase
After tissue injury, the body immediately launches pathways to correct the injury.
Clinically recognizable 5 signs of inflammation:
- Rubor (redness)
- Calor (heat)
- Tumor (swelling)
- Dolor (pain)
- Functio- Laesa (loss of function)
After vascular injury, intracellular calcium is released. This starts the fibrin cascade with fibrinogen forming fibrin by the action of thrombin. The resulting plug acts as a scaffold for the action of platelets. The primary mediator in the inflammatory phase. White blood cells migrate to the area in response to injury. These cells debride the wound on a microscopic level. At the end of this phase, macrophage derived growth factors influence the influx of fibroblasts, keratinocytes and endothelial cells to begin the rebuilding process
Fibroblasts become the dominant cells type peaking at 1-2 weeks. They generate collagen molecules and also cytokines. Collagen is the major component of acute wound healing as they provide strength and structure to the wound.
During this phase endothelial expansion occurs generating angiogenesis for blood vessel formation. Degradation of the fibrin clot is accompanied by formation of granulation tissue. Fibroblastic activity slows transitioning into the Maturation Phase.
Collagen has been deposited randomly into the granulation, now becomes more organized and collagen type 3 is replaced by the stronger collagen type 1. Epithelial cells continue to migrate from the wound edges until the wound is totally covered. At this point, the wound contracts replacing the injured tissue volume with replaced new tissue. This contraction is mediated by the transformation of the fibroblasts to myofibroblasts which contain actin fibers.
Any deterrent to the phases can cause and acute wound to develop into a chronic wound. The common causes mentioned earlier interrupt the normal process.
Proper wound care starts with a history and physical exam as to the etiology of the chronic wound.
- Timing and Onset
- Other factors such as recent medical conditions
- Change in size and drainage
- Pervious treatment with success and failures
- Severity of the pain
- Prior wounds and locations
- Wound assessment as to size location, odor, drainage
- Systemic signs of infection, fever, lymphangitis (red streaking)
- Vascular assessment of the area
- Neurological assessment
- Location in relation to cause, diabetic foot ulcers, pressures ulcers on the sacral area etc.
Assessment includes: laboratory analysis for metabolic causes, vascular analysis of arteries and veins, X-rays to exclude bony involvement, analysis of nutritional status, and culture, only if patient has systemic symptoms as all wounds are contaminated with bacteria.
Once the underlying causes are defined, treatment strategies can then be instituted. Basic care of chronic wounds:
Goal of wound debridement is to remove all infected or devitalized tissue
- Sharp debridement
- Wound Irrigation
- Maggot Application
Hundreds of dressings currently available
- Gauze- good on infected wounds or draining wounds where dressings need to be changed frequently
- Transparent Film Dressings- Allows oxygen to penetrate while allowing moisture to escape. Prevents bacterial contamination but can stick to the wound bed
- Foams- will not adhere to wound bed and absorbent but not suitable for infected wounds
- Hydrocolloids- very absorbent contain methylcellulose or gelatin like material that can swell and when removed will auto-debride the tissue Cannot be used in infection
- Alginates- Derived from sea-weed, highly absorbent and non-adherent so secondary dressing needed. Cause drying
- Bi-layer dermal substitutes- such as Alloderm, Integra, Pelnac, Lando -these products have a porous structure of which the low- level sponge like collagen allows interaction between tissues and biomaterial to permit better bioactivities
- Others- composites, charcoal containing products, antimicrobial containing products, silver containing products, synthetics and multiple variations
- Negative Pressure Wound Therapy- This is an excellent preparation to prepare the wound site for surgical grafting. The wound is covered and a sub-atmospheric pressure is applied
- Hyperbaric Oxygen- Higher than normal oxygen tension anti-infective and promotes tissue growth
- Ozone- Ozone is a gas that can optimize cellular metabolism and because of its antioxidant and antibacterial effects can aid healing of chronic wounds
Grafts transplanted to the wound site. Variety of techniques such as full thickness skin grafts, tissue flap reconstructions, split thickness grafts with mesh expansion, surgical matrix devices from animal sources
Platelet-Rich-Plasma is a concentrate obtained from whole blood which is typically 3-8 times the mean concentration in blood. Platelets secrete several growth factors and proteins that interact with the environment to promote cell differentiation and proliferation responsible for repair and regeneration of tissue. Platelets contain more than 1500 bioactive factors including growth factors, immune system messengers and other enzymes which are vital for tissue repair and wound healing. Platelet-Rich-Plasma is only limited by its rapid action and short absorption into the tissue.
Platelet-Rich-Fibrin is the second generation of platelet concentrates. PRF has been defined as an autologous platelet and fibrin material which has high concentration of platelets with cytokines and immunity promoters. The PRF spontaneously forms a dense fibrin network that enables slower degradation and therefore delayed or prolonged release of growth factors to the surrounding tissue for wound healing and regeneration. The release of growth factors has been reported for at least 7 days and in some studies even longer.
- The Effectiveness and Safety of Platelet-Rich-Plasma for Chronic Wounds: A Systematic Review and Meta-Analysis
Mayo Clin Proc 2021 Sept:96(9): 2407-2417 PMID 34226023
Objective: To evaluate the effectiveness and adverse events of autologous Platelet-Rich-Plasma in individuals with lower-extremity diabetic ulcers, venous ulcers and pressure ulcers
20 randomized controlled trials and 5 observed studies were included
Conclusion: Autologous PRP may increase complete wound closure, shorten healing time and reduce wound size in individuals with lower extremity diabetic ulcers. The evidence was insufficient to estimate an effect on wound healing with other types.
- The Efficacy of Platelet-Rich-Plasma Dressing for Chronic Nonhealing Ulcers: A Meta- Analysis of 15 Randomized Controlled Trials
Plast Reconstr Surg 2019 Dec;144(6):1463-1474. PMID 31764670
Background: Several randomized controlled trials comparing PRP to standard wound care for chronic wounds have been published. Previous articles have revealed that the role of platelet-rich-plasma in promoting chronic wound healing is uncertain. This quantitative meta-analysis was conducted to evaluate whether superior outcomes can be obtained with PRP in non-healing ulcers compared with traditional wound care.
Overall, 630 adult patients in 15 controlled trials were included. The number of ulcers healed in the PRP group was higher than the control and the difference was statistically significant.
Conclusions: Platelet-Rich-Plasma is a valuable and safe treatment dressing for chronic nonhealing ulcers.
- A Mini-Pig Model for Evaluating the Efficacy of Autologous Platelet Patches on Induced Full Thickness Wound Healing
BMC Vet Res 2019 Jun7;15(1) 191 PMID 31174527
Background: Autologous platelet concentrates are currently widely used across different areas of regenerative medicine to enhance wound healing. In this study, they attempted to make a platelet patch using mixture of platelet-rich-plasma and platelet-rich-fibrin to promote wound repair and regeneration
Conclusions: the results demonstrated that this combination of PRP and PRF provided a novel and feasible method for clinical wound care
- Wound Healing: In Vitro and In Vivo Evaluation of a Bio-Functionalized Scaffold Based on Hyaluronic Acid and Platelet-Rich-Plasma in Chronic Ulcers
J Clin Med 2019 Sep;8(9): 1486 PMID 31540446
This study compared the use of hyaluronic acid alone to hyaluronic acid plus platelet rich plasma in the treatment of chronic ulcers and healing.
Hyaluronic Acid is an important element in the extracellular matrix. It interacts with the cell surface receptors. It has the ability to hydrate and modulate the cellular microenvironment. Therefore, HA is a scaffold contributing to the extra cellular matrix and fibrous component.
Platelet- Rich-Plasma contains the growth factors and other factors for tissue repair and regeneration.
Conclusion: When HA was combined with PRP, a superior treatment for chronic ulcer treatment was generated that can reduce the healing period and patient pain and is cost-effective compared to traditional treatment.
Juventix Regenerative Medical provides an easy to use, cost effective, FDA approved PRP Kit that has been scientifically proven to produce repeatable concentrate outcomes from the same donor. Our kits are designed for both safety and effectiveness.
Juventix Regenerative Medical offers a patent pending LED Photoactivator that negates the use of additive substances such as Thrombin and Calcium Chloride, this ensures current federal compliance guidelines.
Juventix Bio-Incubator produces a flowable injectable Platelet-Rich-Fibrin for a wide array of clinical applications and it provides a scaffold for enhanced prolonged tissue regeneration.
Juventix Regenerative Medical has a combination PRP / Hyaluronic Acid Kit which contains non-cross- linked HA that adds to the ease of use and application.
RESTORE, REVIVE, REGENERATE – JUVENTIX REGENERATIVE MEDICAL
Dr. Robert McGrath