Can A New Biologic Matrix Facilitate Improved Wound Healing?

   The field of advanced wound care science continues to deliver new products and concepts for use in healing problem wounds of the lower extremity. The market now includes two living cell products and numerous biologically active products that are the result of bioengineering research and development. The real advantage of these new technologies is that we can now actively stimulate healing whereas most of the prior advances in wound care simply helped to optimize the wound environment.    This ability to interact with the wound base and stimulate the production of local healing is a major advance in science and has already helped countless patients heal their lower extremity wounds. These advanced wound healing techniques attempt to reduce scarring and therefore yield a full thickness and durable wound covering that can better withstand weightbearing and the pressure of shoe gear.    Artificial skin substitutes have become popular because they act as a model for the synthesis of true dermis or epidermis, thereby reducing the amount of scar tissue in the healing wound. Dermal regeneration templates combine a structural scaffold and biologic factors that induce wound regeneration in partial and full thickness wounds.

What You Should Know About The Wound Dressing

   Integra Bilayer Matrix Wound Dressing (Integra LifeSciences) is a tissue engineered bilayer matrix that mimics dermal and epidermal function. The dermal component is a porous biodegradable matrix of bovine tendon collagen and a glycosaminoglycan (chondroitin-6-sulfate) obtained from shark cartilage. This biodegradable matrix provides a scaffold for cellular invasion and capillary growth into the wound defect occupied by the graft material. The collagen-glycosaminoglycan layer is bound to a temporary epidermal substitute layer consisting of a semi-permeable polysiloxane (silicone) layer that controls water vapor loss and provides a covering for the wound. The collagen-glycosaminoglycan matrix becomes vascularized over two to four weeks and is incorporated into the body similar to a full-thickness skin graft.    Integra provides some of the advantages of an autograft without the need of a donor site. This can be a significant factor in this patient population given the concern for creating an additional wound site. Once the collagen matrix has been vascularized in the wound bed and colonized with fibroblasts, the silicone component of the graft will begin to separate. At this point, it can be easily and safely removed. One would then treat the viable wound bed with additional tissue engineered grafting or consider autogenous split thickness graft application.    Integra is indicated for the treatment of partial and full-thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, surgical wounds (wound dehiscence, donor sites/grafts), traumatic wounds (lacerations, second degree burns) and draining wounds. It is contraindicated in patients who have allergies to bovine products or patients with third-degree burns.    Integra interacts with the wound surface by inducing migration of normal fibroblasts and vessels into the collagen matrix while acting as a template for the synthesis of a new dermal matrix. The glycosaminoglycans promote revascularization and engraftment followed by regeneration of autologous dermal tissue. The porous quality of the collagen-glycosaminoglycans network allows infiltration of macrophages, fibroblasts, lymphocytes and endothelial cells derived from the wound to form a neovascular network. An endogenous collagen matrix is deposited via the fibroblasts as the dermal layer of the template degrades (usually over 30 days). Researchers have observed that the structure of the new tissue in the wound base resembles normal dermis rather than random scar tissue.

Pertinent Pointers On Using Integra

   Integra is supplied in a sterile peel-pack container with a phosphate buffer solution. It is an off-the-shelf product and is stable at a room temperature environment. Since this is not a living product, the expiration dates are long and generally do not cause logistical concerns. The technique for proper application of Integra is quite simple and is performed as an outpatient procedure in the operating room or a procedure room.    First, one would debride the wound site free of all necrotic tissue in order to expose a viable and vascular wound bed. If there is exposed bone, curette it to stimulate a small amount of bleeding. Then irrigate the site with a pulse lavage technique and copious normal saline solution. Control bleeding with traditional methods or topical thrombin.    As with split thickness skin grafts, the presence of hematoma will lift the graft off the recipient bed and prevent incorporation of the Integra into the wound bed. The graft is usually meshed 1.5:1 or perforated with a scalpel to avoid hematoma and seroma formation. It is imperative that the graft rest on a clean, well vascularized bed of tissue to promote neovascularization. If the blood supply to the wound bed is poor, vessels will not incorporate into the Integra matrix and the template will fail. Also be aware that placing Integra on a heavily contaminated wound bed can potentially convert an open colonized wound into a closed wound abscess. If you are concerned about the wound base, obtain culture samples. One may place Integra over deep wound tissues including bone, fat, fascia, tendon and muscle.    When applying the Integra graft to the wound site, clinicians should ensure it is cut to fit accurately within the excised wound margins. Note the orientation of the graft and ensure that the collagen-glycosaminoglycan dermal layer is in direct contact and adherent to the wound bed with no air spaces occluding graft contact. Place the silicon layer (identified by the black marker threads) away from the wound so this forms the superficial protective layer. Secure the graft to the wound margins with several staples or sutures.    One can then dress the graft with a non-adherent dressing (Mepitel, Adaptic, Tegapore) and subsequently use an antibacterial barrier dressing layer (Acticoat, Actisorb). One may then employ a secondary dressing or consider applying negative pressure (i.e. VAC therapy).    The non-adherent layer will serve to prevent premature disruption of the graft during dressing changes. The antibacterial layer will protect from infection and decrease wound contamination, and the negative pressure will stimulate graft adherence and angiogenesis while reducing the incidence of seroma and hematoma.

Final Notes

   Multiple clinical studies show that burn wounds treated with Integra progress to normal re-growth of papillary and reticular dermis without scar formation. Studies comparing Integra versus epidermal autografts for the treatment of burn patients show the Integra dressing has a higher percentage of take. Integra take rates are reportedly between 80 and 87 percent. The reported success rate of overlying split thickness skin grafts on top of the Integra generated dermis is 85 percent.    While there is only minimal experience and data in using Integra for complicated diabetic foot wounds, there appears to be significant promise. The product has minimal logistical concerns since it is not a living tissue and can help build a viable wound matrix in problem and deep wounds in the lower extremity. Dr. Anderson is the Chief Resident at the INOVA Fairfax Hospital Podiatric Residency Program in Falls Church, Va. Dr. Steinberg (pictured) is a faculty member of the Department of Surgery at the Georgetown University School of Medicine in Washington D.C.
 

References:

1. Molnar JA, DeFranzo AJ, Hadaegh A, Morykwas MJ, Shen P, Argenta LC. Acceleration of Integra Incorporation in Complex Tissue Defects with Subatmospheric Pressure. Plastic and Reconstructive Surgery 113(5); 1339 – 1346, 2004.
2. Ryan CM, Schoenfeld, DA, Malloy M, Schulz III JT, Sheridan RL, Tompkins RG. Use of Integra artificial skin is associated with decreased length of stay for severely injured adult burn survivors. J Burn Care Rehabil. 2002 Sep-Oct;23(5):311-7.
3. Yannas IV and Burke JF. Design of an artificial skin. Basic design principles. J Biomedical Materials Research 14; 65-81, 1980.
4. Yannas IV. Studies on the biological activity of the dermal regeneration template. Wound Repair and Regeneration 6 (6); 518-523, 1998.
5. Heimbach D, Luterman A, Burke J, Cram A, Herndon D, Hunt J, Jordan M, McManus W, Solem L, Warden G, Zawacki B. Artificial Dermis for Major Burns. Annals of Surgery 208(3); 313 – 320, 1988.