Olean General Hospital

Human knowledge is growing exponentially. This explosion is clearly evident in the field of Medicine. We hear almost daily about advances in cardiovascular and oncologic treatments. Medicine appears to be on the verge of extending human life well beyond 100 years. Fortunately, Wound Care physicians and their patients are also reaping the benefits of this rapid knowledge advancement. In the last decade, key elements in the body’s cellular healing processes have been elucidated. A major thrust has been in the development of human tissue therapies.

Wounds heal in an orderly and progressive set of overlapping phases (Fig. 1). Failure of these normal processes will lead to formation of a chronic ulcer (defined as non-healing after 30 days). Recent trends in chronic wound care have been in the use of “biologic” grafts to help restore the normal healing sequence.

Fig. 1 Normal Phases of Wound Healing

What can cause disruption of the healing process? We can look at two distinct reasonsa) patient (host) factors and b) local wound factors. Patient factors include such issues as arterial insufficiency, uncontrolled diabetes, excessive edema, infection, immunosuppression, hypoxia and poor off loading. Most wound physicians understand that these host factors must be optimized for proper healing. We will leave discussion of the se host dynamics for another time.

Let’s look at the local wound factors involved in healing. This is where the use of cellular therapy comes into play.

"Given the best treatments available most Wound Care physicians heal at best 70-80 percent of patients. Obviously, we are still missing the mark."

Inflammatory Phase

This “cleaning” phase of wound closure follows the initial phase; Hemostasis. White blood cells (neutrophils and macrophages) will remove by phagocytosis necrotic debris and devitalized tissue. These cells also provide an orderly release of inflammatory chemical mediators into the injured tissues. These mediators act at the cellular level to signal the body to continue the healing process. Most chronic wounds become “stuck” in this inflammatory phase of healing. What prolongs this phase? Current thinking is most likely the production of biofilm. Biofilm is a dense layer of planktonic bacteria encased in an extracellular matrix of polysaccharides. It is very resistant to common treatments including both systemic and topical antimicrobials. It is best treated by a biofilm based wound care approach; sharp debridement along with topical antimicrobial therapy. Antimicrobial agents utilized to attack biofilm include; quaternary ammonia compounds, hypochlorite, silver, topical antibiotics, polyhexalmethene biguanide (PHMB) and iodine. These are variously effective.

Today, topical care now comes in the form of new collagen/antimicrobial products. These are now being utilized to attack this biofilm layer. Sharp debridement mechanically removes the biofilm. The topical collagen/antimicrobial graft is then applied. The collagen component acts like a “sponge” to absorb excess inflammatory mediators thus assisting in restoring the natural balance in these signaling molecules. The antimicrobial portion then reduces the bacterial bioburden. Since biofilm will rapidly reform (3-5 days), the sequence of debridement and graft application is usually repeated on a weekly basis. Provided the host factors are controlled, most chronic wounds (70-80 percent) will respond with restoration of the natural sequence of “signaling” and move into the next phase of healing; the proliferative phase.

Proliferative Phase

Ulcers can also become stuck in the proliferative phase of healing. Here angiogenesis, granulation formation and early epithelialization fail to occur. Again, the bodies organized sequence of healing is disrupted. Orderly chemical signaling is upset. In addition, ulcers trapped in the proliferative phase also lack the cellular components needed for proper healing. Wounds caught in this phase of healing can be helped with the use of a variety of amniotic based tissue grafts.

Amniotic grafts are produced in one of two forms; acellular or cellular. Both types will assist in restoring wound cellular signaling. Both provide a wound matrix of collagen that will help absorb excess inflammatory proteins. They can also provide and preserve growth factors already present in the ulcer bed. These growth factors in turn will signal the body’s host cells to migrate and proliferate in the wound. Once stimulated, the host cells hopefully continue the healing cascade.

Additionally, cellular products can provide a source of mesenchymal stem cells (MCS). These specialized cells not only provide cellular signaling mechanisms but can also differentiate into several types of end cells. Signaling will attract host fibroblasts and keratinocytes; fibroblasts to lay down collagen and keratinocytes to form new epithelium. However, MSC’s can also differentiate into healing types of cells thus providing a source of direct cellular treatment. Studies have shown that patients with chronic non-healing ulcers lack healthy, active MCS’s. Fresh amniotic grafts will provide an exogenous source of these needed cells.

Summary

Chronic ulcers fail to heal for multiple reasons. Uncontrolled host problems remain a major issue: arterial insufficiency, poorly controlled diabetes, peripheral edema and offloading are key factors.

For ulcers caught in the inflammatory phase of healing biofilm based wound management utilizing mechanical debridement with collagen/antimicrobial based grafts appears to provide the physician with a powerful new treatment option.

Ulcers failing in the proliferative phase can now be managed using amniotic based tissue grafts. These products help restore chemical signaling, attract host MSC’s and can provide a source of exogenous MCS cells that can differentiate into new healing tissue.

Unfortunately, modern day wound care is not all or none. Given the best treatments available most Wound Care physicians heal at best 70-80 percent of patients. Obviously, we are still missing the mark. Our understanding of chronic wound treatments is not complete. Future trends will come as our knowledge base continues its exponential growth.

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