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Why Some Wounds Become Chronic?

There are four distinct but overlapping stages of wound healing. To differentiate between acute and chronic wounds, it is important to understand these phases and what can go wrong:

stages of wound healing

Hemostasis:

  • Clot that is formed initially at the site of injury to control bleeding & comprised mainly of platelets.
  • Many conditions can interfere with the formation of a clot during hemostasis, such as venous insufficiency, diabetes, thrombocytopenia, and other blood dyscrasias.
  • Conditions such as these may lead to poor wound healing, therefore careful management of these conditions will be important in the normal process of wound healing.

Inflammation:

  • Within hours of clot formation, neutrophils travel to the site of injury and adhere to the endothelial cell walls of the damaged vasculature. These neutrophils provide protection against infection as they phagocytize bacteria, dead tissue, and any foreign material present.
  • Neutrophils also produce inflammatory mediators that activate and recruit fibroblasts and epithelial cells to the injury site.
  • When neutrophils are depleted, they are replaced by macrophages, which help to rid the wound of devitalized tissue and produce elastase and collagenase.
  • Macrophages also prompt an ending of the inflammatory phase and the beginning of the proliferative phase of wound healing.
  • Unfortunately, inflammatory mediators can cause tissue damage and may sometimes prolong the inflammatory phase of healing. Therefore, any process which increases neutrophils (and thus inflammatory mediators) can lead to prolongation of the inflammatory phase, which may be evident to the astute clinician as an increase in exudate. When wounds are stalled in the inflammatory phase, proper management of exudate is an important step in assisting wounds with moving on to the proliferative phase.

Proliferation:

  • During this stage, the wound decreases in size and fills with new connective tissue (contraction, granulation, and epithelialization).
  • Granulation tissue is composed of fibroblasts, macrophages, blood vessels, immature collagen, and an extracellular matrix. As macrophages begin to decrease in number, other cells, including keratinocytes, fibroblasts, and endothelial cells, begin to produce and release growth factors and continue to multiply.
  • As granulation tissue grows, it stimulates collagen production and fibroblasts, which provide the new scaffolding by promoting the migration of endothelial cells and fibroblasts into the wound. The growth of granulation tissue results in the filling of the wound and narrowing of wound margins. Eventually, the wound closes off and forms a scar.
  • During the proliferation phase, maintenance of a moist wound environment and protection of newly growing tissues is crucial. Any process or condition that interferes with either of these may result in prolongation of the proliferation phase.

Remodeling:

  • In this phase, collagen remodels, proliferates, and matures, a process that can take many months. Tensile strength increases but will never achieve the strength present before the injury occurred. At best, tensile strength may be 80%.

Chronic Wounds vs. Acute Wounds

  • An acute wound is defined as a recent wound that has yet to progress through the sequential stages of wound healing. It is acquired because of an incision or trauma and heals in a timely and orderly manner.
  • On the other hand, a chronic wound is one that fails to progress through a normal, orderly, and timely sequence of repair, or in which the repair process fails to restore anatomic and functional integrity after three months.

If untreated, chronic wounds can result in further complications including infection, which causes inflammation and pain. Factors contributing to the chronicity of the wound may include: Pressure, trauma, and/or lower extremity wounds, Increased bacterial load, Excessive proteases: Degraded growth factors, matrix metalloproteinases (MMPs), degraded cell surface structures, Senescent/Aberrant cells, Inappropriate treatment.

What makes a wound a chronic wound?

  • Inflammatory mediators: Increased levels of inflammatory mediators result in damage to growth factors and the extracellular matrix that are necessary for healing to take place. If we were to examine most chronic wounds at the cellular level, we would likely find an imbalance in cytokines, growth factors, and/or MMPs.
  • Wound infection: Bacteria release enzymes and MMPs that reduce growth factors and degrade the fibrin necessary for healing. Bacteria increase the inflammatory response, and chronic wounds often have high levels of bacteria present in the wound. Reducing the bacterial burden will improve the chances of healing.
  • Biofilm: A biofilm is a complex structure of microorganisms that can adhere to a surface, which protects the bacteria contained in it. As we learn more about biofilms, it is becoming increasingly apparent that biofilms play a large role in the production and maintenance of the chronic wound environment.
  • Hypoxia: Hypoxia impedes wound healing and allows certain negative entities, such as bacteria, to flourish. Hypoxia impedes fibroblast proliferation and collagen production, both of which are crucial to wound healing. Many common chronic conditions result in hypoxia, including cardiovascular disease, smoking, pulmonary diseases, and peripheral vascular disease (PVD). Attention to proper management of these conditions can improve wound healing.
  • Poor nutrition: A diet that does not provide enough protein will lead to delayed wound healing. Wounds will remain in the inflammatory phase of healing if the patient remains in a catabolic state, which causes decreased fibroblast formation. Improving the patient’s diet can improve wound healing and change a chronic wound into a wound with the possibility of healing completely. Whether the patient cannot afford to eat well, is unable to prepare nutritious food, or has anorexia due to a disease state, the clinician should make every effort to identify and overcome any barriers to adequate nutrition.

There are, of course, other factors that influence wound healing, but these are some of the most important ones.

Market overview

According to MarketsAndMarkets, the global wound care market is projected to reach USD 24.8 billion by 2024 from USD 19.8 billion in 2019, at a CAGR of 4.6% from 2019 to 2024. The advanced wound care products segment dominated this market in 2019 and is expected to have the highest growth.

bar chart showing wound care market value 2019 to 2024 in usd

Emerging economies such as India, China, and Brazil are expected to provide a wide range of opportunities for players in the industry.

Treatment

When it comes to chronic wounds, it is obvious that attempting to determine the underlying cause of failure to progress in a timely fashion through the stages of healing is the key to turning a chronic wound into a healing wound. However, using advanced wound care products help to shorten the healing time, optimizing drainage, and reducing the risk of infection.

BMG Pharma provides a comprehensive range of advanced wound care products based on its patented Hyaluromimethic® technology (biomaterials derived from modified sodium hyaluronate) to help professionals to manage these types of wounds.

This product range includes two unique products to address different types of wounds:

  • Lipohyal Wound Care Solution is a wound irrigation solution indicated for the topical treatment of dermal lesions, acute and chronic wounds such as diabetic foot, decubitus, lower limb, and vascular ulcers.
  • Lipohyal Wound Care Spray is a dry powder spray indicated for the treatment of uninfected acute dermal lesions (i.e. abrasions, bruising, fissures, cuts, small surgical wounds, localized first- and second-degree burns), on diabetic foot ulcers, and decubitus ulcers.

Lipohyal’s technology

Silver ion (Ag+) has a broad antimicrobial spectrum and is cytotoxic to bacteria, viruses, yeast, and fungi. Ag+ binds to DNA, RNA, and various proteins, leading to cell death via multiple mechanisms, such as protein and nucleic acid denaturation, increased membrane permeability, and the poisoning of the respiratory chain. For this reason, resistance against the silver ion has only rarely been reported.

The silver ion has great antimicrobial and bactericidal properties, but it is also toxic to fibroblasts when present in high concentrations. Injudicious use of silver-containing dressings can lead to impaired wound healing.

Silver used in Sodium Hyaluronate Lipoate Silver Complex (SHLS) forms a stable three-dimensional matrix that creates an ideal moist microenvironment that promotes healing while having a barrier effect against bacterial penetration. Products based on this novel biomaterial release silver ions into the wound in a sustained fashion without causing cytotoxicity.

molecular structure sodium hyaluronate lipoate silver complex (SHLS)

Clinical evidence

An Italian multicenter study was performed on 25 patients and 29 wounds to evaluate the wound healing effect of a product based on Sodium Hyaluronate Lipoate Silver Complex (SHLS).  Descriptive statistics and graphs have indicated a good performance of the medical device in the reduction/healing of wounds.

  • The area of the wounds decreases as time goes by, at visit 2 the mean area is 6.2 cm2 and it drops constantly over time until it reaches the mean value of 2.4 cm2 at visit 6. At visit 3 the relative change of wound area from baseline is 16.4% and it doubles at Visit 4 (32.7%); at visit 5, on average, the wound area has halved the baseline value. At the end of the study, the mean decrease in the area is 67.2%.
  • Wound depth decreases over time: at visit 2 the mean value is 3.48 mm and it drops to 1.38 mm at Visit 6. The maximum depth value has been registered at Visit 2 and it was 10 mm.
  • Red wounds decrease over time from 62% to 28% (at Visit 2 and Visit 6 respectively), yellow ones from 14% to 3%, and white ones from 17% to 7%. Healed wounds (evaluated by color) are 10% in Visit 5 and 38% in Visit 6.
  • VAS score time trend indicates an improvement in subjects’ condition regarding the pain. The percentage of wounds in class 0 (0=no pain) increases notably over time: mean values go from 38% at Visit 2, to 52% at Visit 3, 76% at Visit 4, 86% at Visit 5 and 93% in Visit 6. To be noted are also the percentage of wounds in class 2: they are 24% at Visit 2, become 3% in Visit 5, and disappear at Visit 6.
clinical evidence lipohyal wound care range

Lipohyal comprehensive range of advanced wound care products is a viable solution for the management and treatment of different types of acute and chronic wounds.

References:

  1. Richard A.F. Clark, in Principles of Tissue Engineering (Fourth Edition), 2014
  2. Bowers S, Franco E. Chronic Wounds: Evaluation and Management. Am Fam Physician. 2020;101(3):159-166.
  3. “The Four Stages of Wound Healing” https://www.woundsource.com/blog/four-stages-wound-healing, Accessed on July 7, 2020.
  4. American Society of Plastic Surgeons. Evidence-based Clinical Practice Guideline: Chronic Wounds of the Lower Extremity. https://www.plasticsurgery.org/Documents/medical-professionals/health-policy/evidence-practice/Evidence-based-Clinical-Practice-Guideline-Chronic-Wounds-of-the-Lower-Extremity.pdf, Accessed on July 10, 2020.
  5. Krasner D. Chronic Wound Care 5. HMP Communications; 2012.
  6. The Angiogenesis Foundation. Types of Chronic Wounds. Science of Wound Healing. 2012. Accessed on July 2, 2020.
  7. The Wound Healing Society. Chronic Wound Care Guidelines. https://woundheal.org/files/2017/final_pocket_guide_treatment.pdf, Accessed on June 26, 2020.
  8. Werdin F, Tennenhaus M, Rennekampff HO. Evidence-based Management Strategies for Treatment of Chronic Wounds. Eplasty. 2009; 9: e19.
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