A Comprehensive Review Of Topical Agents

Start Page: 40

Understanding The Phases Of Wound Healing

1. Coagulation phase: 0-2hrs. At a site of injury, exposed basal lamina collagen (type IV) activates plasma thrombin to cleave fibrinogen and form a fibrin mesh. The fibrin mesh traps platelets, which aggregate, modify and degranulate, releasing pro-inflammatory agents that include platelet-derived growth factor (PDGF). PDGF is a chemoattractant for neutrophils, macrophages and fibroblasts.

2. Inflammatory phase: 0-3 days. Neutrophils, the first leukocytes to arrive in the wound space, remove necrotic debris and kill bacteria. In a respiratory burst, neutrophils consume oxygen and secrete peroxidases for microbial killing. After 24 hours, macrophages/monocytes predominate to regulate inflammation and tissue repair. They further remove bacteria and debris. Activated macrophages release growth factors that promote angiogenesis, granulation tissue formation and cross communication with B-cell and T-cell mediated immune responses. Studies show the need for neutrophil “priming” to facilitate proper macrophage growth factor effect.

3. Proliferation phase: 3-21 days. Macrophages secrete transforming growth factor beta (TGF-ß), which enhances fibroblast differentiation and proliferation. Fibroblasts, the predominate cell type found in granulation tissue, produce extracellular matrix and collagen scaffolding, a strut for granulation (type I in most tissues). Extracellular matrix (ECM), composed of hyaluronic acid, fibronectin and glycoproteins, regulates granulation tissue fluid composition and is fundamentally important in orchestrating cell-cell interaction, proliferation, migration, differentiation and adhesion.

As granulation tissue develops, blood vessels invade the collagen scaffolding. This process of angiogenesis is directed through macrophage-released vascular endothelial growth factor (VEGF). Macrophages also secrete matrix-modifying enzymes, matrix metalloproteases (MMP), which degrade local cellular attachments to collagen/gel matrix. Fibroblast and keratinocytes are freed to migrate. Epithelialization proceeds as keratinocytes divide and migrate, covering the wound bed.

4. Maturation phase: two weeks-years. The invasion of tissue-specific cells, wound contraction and collagen deposition typifies maturation. Maturing adult wounds heal by scarring with significant collagen deposition and a 20 percent reduction in strength. Conversely, neonatal wound maturation produces supple, stronger tissue with less collagen deposition. TGF-ß appears to regulate the amount of hyaluronic acid, collagen deposition and scarring. TGF-ß1 is associated with neonatal tissue regeneration while TGF- ß3 is more commonly associated with adult tissue repair.

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Here you can see a status post open first ray amputation. Panafil treatment has been initiated.
Here you can see the same wound five weeks after treatment with Panafil began. Note the healthy red granular base.
Here is the same wound approximately eight weeks after the first application of Panafil. As you can see, the wound is close to closing.
Here is a plantar forefoot ulceration right at the start of Hyaff dressing therapy.
Four weeks later, you can see the healed ulceration site.
Several studies have shown that Becaplermin promotes healing in diabetic neuropathic wounds as part of a comprehensive program of debridement, infection control and pressure reduction.
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Author(s): 
By Jonathan Moore, DPM, MS, A. Patti Smith, MD, and John S. Steinberg, DPM

The wound is in constant evolution. Changes arise and you need to be able to respond accordingly in your treatment course. Indeed, understanding the biochemical dynamics of wound healing is vital for proper product selection (see “Understanding The Phases Of Wound Healing” on page 42). The challenge to the practitioner is to have the knowledge base with which to sort through the thousands of topical agents and dressings available today.

Insights On Topical Agents With Collagen
Let’s start out with a discussion of the biologic topical agents that contain collagen. Collagen hastens wound healing and works best when you apply it in the woven sheet format.
1. Kollagen (BioCore). These products are 100 percent non-denatured bovine collagen type I in proper configuration specific to skin tissue.
2. Medifil (BioCore). Of these products, you can use Medifil particles for draining, undermined, tunneled, infected or contaminated deep cavity wounds. Medifil pads are for deep cavity draining wounds. You may use Medifil gel to help treat dry, tunneled, superficial, minimally draining wounds.
3. Skin Temp (BioCore). Skin Temp (porous collagen sheets attached to a nonadherent backing) is also indicated for dry, superficial draining wounds.

4. Fibracol (Johnson and Johnson). Fibracol is a non-adherent, collagen-based dressing (90 percent) that is combined with calcium alginate (10 percent). It’s indicated for moderate to heavy exudative wounds, ulcers or dehisced incisions. It helps maintain a moist wound environment while allowing exudative transmission to prevent maceration.
5. Collagen Wound Gel (Johnson and Johnson). NU-GEL promotes natural autolysis by rehydrating and softening necrotic tissue while providing a moist wound environment.
6. Collagen Dressings. Another option is hyCure, a 96 percent type I collagen. It’s a hydrolyzed protein powder that forms a gel in the wound bed. It acts as a wound filler and exudate absorber.
7. Oasis (Healthpoint). Oasis offers a sterile wound covering to support tissue regeneration in partial thickness wounds. It provides a tissue-engineered collagen matrix derived from porcine small intestine submucosa (SIS). Oasis has a one-year shelf life and is available in single thickness, fenestrated sheets.

What About Hyaluronic Acid?
Hyaluronic acid is another biologic topical agent you should consider. Hyaff (ConvaTec) is an ester of hyaluronic acid (60 percent). As an essential component of the wound matrix, hyaluronic acid facilitates growth and movement of fibroblasts as well as controlling hydration. Use it for closure of sinuses and improved healing of indolent neuropathic ulcers. Hyalofill F is a non-woven fleece-like material. Hyalofill R is a rope-like material. You can use either of these as topical wound dressings, creating a hydrophilic gel rich in hyaluronic acid.

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