Wound care in the US is a national health problem. In the United States, Chronic ulcers cost $28.1 Billion for the Medicare population alone. When the analysis included wounds as a secondary diagnosis the cost increased to $31.7 million.
It is estimated 8.2 million Americans are living with a chronic or non-healing wound. This is about 15% of the Medicare population.
The annual growth rate from 2023-2030 is expected to be a minimum of 4.15%.
Medicare budget for all wound treatments including infection management ranged from $28.1 billion to $96.8 billion with a significant portion contributed by surgical wounds and diabetic ulceration.
According to a market research study, due to advancing technology, expensive wound care therapies and an increasing geriatric population, the wound closure and dressing market alone will expand to $22 billion in 2024.
Due to this huge economic burden of wound care, there is a great demand for effective, economical and side effect free healing strategies.
Causes of chronic wounds
- Advanced age
- Immobility or inactivity
- Nerve damage
- Overall poor health, diet nutrition
- Smoking or alcohol abuse
- Metabolic conditions such as diabetes
Types of chronic wounds
- Nonhealing, infected surgical or traumatic
- Venous/arterial ulcers
- Pressure ulcers
- Diabetic foot ulcers
- Ischemic ulcers
Most common types of ulcers
Venous and arterial ulcers develop after damage to a vein especially in the distal areas of the legs and ankles. Chronic venous disease such as varicose veins or chronic venous insufficiency contributes to the development of ulceration. Edema due to the venous disease aids the skin breakdown and speeds development of this disease.
Arterial ulcers develop due to lack of circulation and thus lack of oxygen to the tissues. Any disease-causing damage to the arterial circulation depriving adequate blood flow to the skin and underlying tissues will lead to an open wound.
Pressure ulcers are injuries to the skin after prolonged pressure, friction and moisture on a part of the body. These ulcers, commonly called “bed sores”, occurs in areas of bony prominences such as the heels, ankles, coccyx and hips.
Prolonged pressure causes these areas to be deprived of oxygen from decreased circulation and as a consequence the skin starts to degrade.
Obesity will compound the pressure especially if confined to bed due to injury, age or illness.
Urinary or bowel incontinence adds to the moisture in the environment. Poor nutrition increases the risk and lack of healing potential of these ulcers.
If left untreated, these ulcers often penetrate to deeper tissues such as the muscle and bone.
Diabetic wounds and ulcers are increasing in the diabetic population. Patients with diabetes have a 15-25% chance of the development of a chronic wound. The reason for the high incidence is diabetes causes vascular changes in the vessels. The narrowed vessels provide decreased circulation to the tissues and lack of oxygen and nutrients limits the ability of the body to repair and regenerate the tissue.
Diabetes also affects the nerves causing decreased sensation and therefore contributes to trauma that cannot be felt.
Chronic inflammation and immune system problems in diabetics which are both side effects of this disease can contribute to slow hearing of damaged tissue.
Recent group of experts, after review of the current literature, agreed that when the standard of care is applied to a wound with failure to progress towards healing within 4 weeks, the wound should be considered chronic.
A time related assessment has also been applied to the process of healing a wound that has been diagnosed as chronic. If during the 4 weeks of standard of care and the wound surface is reduced by 50%, the wound is likely to heal on the same treatment in 12 weeks. If less than 50% reduction occurs in 4 weeks, it is unlikely to heal on this treatment regime and reassessment and or additions or change of treatment should be considered.
Debridement is the removal of non-viable tissue including necrotic tissue, slough and biofilm.
The ladder of debridement starts at the simple on the bottom to the most complex on the top.
Experts agree that early aggressive, initial and serial debridement is the cornerstone of wound care.
All chronic wounds are infected with bacteria. Not all surface bacteria result in infection or even contribute to the chronicity of the wound. Therefore, cultures can be misleading. The identification of a species by culture may not be a pathologic bacterium.
Treatment with antibiotics should be limited in duration and only used in certain cases.
The main functions of a dressing are protection, moisture/exudate management, pain control, aesthetics, compression, and offloading/immobilization. Cell and tissue-based dressings add production of growth factors.
- Protection- Dressings provide protection from further tissue trauma and can prevent further contamination of the wound.
- Moisture management- excessive moisture due to exudate inhibits cell proliferation and breaks down matrix components. If the wound is dry, dressings can provide moisture such as hydrogels or impregnated gauze.
- Pain reduction and aesthetics- Dressings will greatly reduce pain by reducing inflammation, evaporation and heat loss. Dressings will also help with the scar formation by downregulating inflammatory cytokines and reducing hypertrophic scarring.
- Compression-This is essential in areas of chronic edema to enhance venous return and reduce hydrostatic pressure
- Offloading- any wound caused by pressure between a bony prominence and a hard surface needs to be offloaded in order to heal. Immobilization may be necessary if a tendon is exposed or after a grafting procedure.
Grafting is a surgical procedure where tissue is moved from one site to another without bringing its own blood supply with it. Therefore, the wound bed must be well prepared, highly vascular with no exposed structures and no infection.
Grafts may be human tissue or non-autologous grafts.
Autologous skin grafts
- Split thickness grafts- advantages are replace like with like, donor site usually heals within 2-3 weeks, consists of epidermis and dermis
- Full thickness grafts- advantages are good match when color is needed such as facial wounds and contracture is less upon healing
- Epidermal grafts- advantages are alternative to traditional autografts when only epidermis is needed, also can be used to augment healing
- Composite grafts- used for structural support usually include cartilage included when skin alone is not enough volume or extra support is necessary
- Cellular allografts are laminated constructs with epidermal/dermal layers from another human.
- Decellularized or acellular allografts consist of collagen substrates that reportedly act as a template for cellular ingrowth.
- Allografts derived from human placentas may come from amnion, chorion or umbilical cord. These acts as delivery vehicles for growth factors.
- Xenografts from other species such as bovine, porcine, equine and fish products.
- Synthesized and composite allografts
Advantages of Non-autologous grafts
- No donor sites
- Application can be done in the office
- Promotes healing by induction of growth factors and cytokines
- Pain reduction
- Provide a physiological cover of the site
- Reduce loss of moisture
Platelet Rich Plasma/Platelet Rich Fibrin
It has been proven that the regenerative potential of the platelets concentrated in platelet rich plasma can serve as an appropriate method for wound healing.
Platelets are anucleated blood components formed in the bone marrow and released into the circulation where they circulate for 7-10 days. When signaled, platelet modulate hemostasis and thrombo-inflammation.
Platelets secrete large amounts of cytokines and growth factors from their granules. This secretion contains ample amounts of cytoplasmic granules, lysosomal content, microparticles and exosomes that play a pivotal role in the regulation of wound healing signaling mechanisms.
The growth factors and cytokines released from the platelets promote proliferation, differentiation and migration of cells such as fibroblasts, epithelial, endothelial and mesenchymal stem cells and are responsible for wound healing. They are all involved in hemostasis, angiogenesis, collagen synthesis and revascularization of the damaged tissue.
Platelets accommodate several secretory cytoplasmic, lysosomal granules, microparticles and exosomes which release various factors that are all significantly involved in the wound repair mechanism.
Collectively they are called the platelet secretome and contain growth factors, cytokines, adhesive molecules, chemokines and other signaling molecules.
The secretome regulates diverse biochemical, molecular, and cellular aspects of the wound and modulates inflammation, recruitment of neutrophils and macrophages while promoting angiogenesis, extra cellular matrix formation and overall tissue repair and remodeling.
After activation, platelets shed small microparticles called platelets dust. These promote stem cell progenitors and contain several proteinaceous wound healing factors like RANTES (regulated upon activation normal T cell expressed and presumable secreted). RANTES is a chemokine secreted by platelets to promote the migration of leukocytes especially T cells.
The leukocytes have multiple responses involved in tissue regeneration.
Platelets also secrete exosomes by direct exocytosis. Exosomes are rich in various micro -RNA’s. These exosomes positively influence wound healing.
In chronic diabetic ulcers, excess reactive oxygen species (ROS) are generated resulting in an imbalance between pro-inflammatory and anti-inflammatory cytokines. PRP contains a high concentration of growth factors and cytokines that maintains ROS levels and reduces wound recovery time. Subcutaneous PRP administration in patients suffering from non-healing ulcers demonstrated decreased wound size, pain and inflammation.
In another study of 150 patients diagnosed with diabetic foot ulcers, after topical application of PRP, a significant granulation tissue formation and early wound closure was observed.
For efficient closure of wounds, proper regulation of granulation tissue formation, angiogenesis, collagen synthesis and epithelization is needed. In a canine model, intra-lesion PRP was administered into full thickness skin defects. They observed improved tissue perfusion that uplifted granulation tissue formation and attracted nutrients and oxygen into the wound. This led to rapid healing.
Since 1990, platelets derived products have been efficiently used in all fields of regenerative medicine. Over the past few years, platelets are continuously in the forefront of multiple clinical challenges such as wound healing and studies have proven this cost-effective treatment modality. PRP has a potent impact of cost reduction and is quickly becoming a potential replacement for other therapies in chronic wound therapies.
Juventix Regenerative Medical is an industry leader in the regenerative medical field. Our Platelet Rich Plasma Kits are FDA approved and designed for safety, sterility and effectiveness. They are cost effective and easy to use. Our kits have been scientifically manufactured to provide a consistent platelet concentrate, devoid of red blood cells with a minimum number of leukocytes critical to the regenerative cascade.
Juventix Regenerative Medical offers a patent pending LED Activator to activate the platelets and begin the regenerative process. The activation is a critical step in the release of cytokines, growth factors and bioactive proteins and is accomplished with LED light. This negates the use of chemical additives such as Calcium Chloride, Thrombin or Collagen.
Juventix Regenerative Medical supplies a Bio-Incubator that transforms Platelet Rich Plasma into an injectable Platelet Rich Fibrin. The Platelet Rich Fibrin, commonly called “the second generation of platelet products” has different growth factors and cytokines than original PRP. These different cytokines provide a broader range of clinical uses due to their anti-inflammatory properties.
RESTORE, REVIVE, REGENERATE- JUVENTIX REGENERATIVE MEDICAL
Dr. Robert McGrath
Int J Mol Sci 2020 Oct 21;21(20):7794 PMID 33096812
- Improving Chronic Diabetic Wound Healing Through an Injectable and Self -Healing Hydrogel with Platelet Rich Plasma Release
ACS Appl Mater Interfaces 2020 Dec 16;12(50):55659-55674. PMID 33327053
- The Effectiveness and Safety of Platelet Rich Plasma for Chronic Wounds: A Systemic Review and Meta-Analysis
Mayo Clin Proc 2021 Sept;96(9):2407-2417 PMID 34226023
Eur Surg Res 2021;62(1):1-9 PMID 33621973
Wound Repair and Regeneration/vol 30,issue 2/156-171 doi.org/10.1111/wrr.12994