Foot Ulcer Example Picture

Foot Ulcers and Infections

Diabetic foot ulcer is one of the major complications of Diabetes mellitus. It occurs in 15% of all patients with diabetes and precedes 84% of all lower leg amputations. Major increase in mortality among diabetic patients, observed over the past 20 years is considered to be due to the development of macro and micro vascular complications, including failure of the wound healing process. Wound healing is a "make-up" phenomenon for the portion of tissue that gets destroyed in any open or closed injury to the skin. Being a natural phenomenon, wound healing is usually taken care of by the body's innate mechanism of action that works reliably most of the time.

Key feature of wound healing is stepwise repair of lost extracellular matrix (ECM) that forms largest component of dermal skin layer. Therefore controlled and accurate rebuilding becomes essential to avoid under or over healing that may lead to various abnormalities. But in some cases, certain disorders or physiological insult disturbs wound healing process that otherwise goes very smoothly in an orderly manner. Diabetes mellitus is one such metabolic disorder that impedes normal steps of wound healing process. Many histopathological studies show prolonged inflammatory phase in diabetic wounds, which causes delay in the formation of mature granulation tissue and a parallel reduction in wound tensile strength.

Foot Ulcers and Infections Treatment

Non-healing chronic diabetic ulcers are often treated with extracellular matrix replacement therapy. So far, it is a common trend in diabetic foot care domain to use advanced moist wound therapy, bio-engineered tissue or skin substitute, growth factors and negative pressure wound therapy. No therapy is completely perfect as each type suffers from its own disadvantages. Moist wound therapy is known to promote fibroblast and keratinocyte proliferation and migration, collagen synthesis, early angiogenesis and wound contraction. At present, there are various categories of moist dressings available such as adhesive backing film, silicone coated foam, hydrogels, hydrocolloids etc. Unfortunately, all moist dressings cause fluid retention; most of them require secondary dressing and hence are not the best choice for exudative wounds. To address the physiological deficiencies underlying diabetic ulcer, various tissue engineering technologies have come up with cellular as well as acellular skin replacement products.

Cellular Wound Matrices

These type of matrices are used as dermal or both dermal-epidermal substitutes. They are made up of In vitro cultured fibroblasts or keratinocytes onto a biomaterial mesh. As cells proliferate across the mesh, they secrete human dermal collagen, matrix proteins, growth factors and cytokines to create three-dimensional human dermal substitute containing metabolically active living cells. Thus by restoring the dermal tissue, they cause patient's own epithelial cells to migrate and close the wound. Unlike dermal substitutes, dermal-epidermal substitutes have a combined dermal and epidermal layer. The epidermal layer is composed of live, differentiating keratinocytes, while the dermal layer consists of living fibroblasts.

Acellular Wound Matrices

Along the same line, some diabetic wounds may be treated by application of natural or synthetic acellular wound matrices that act as a scaffold at the tissue site to promote fibroblast and keratinocyte migration, to assist in wound closure and thus provide an optimal environment for a restoration of tissue structure and function. These matrices come in different forms.

  1. Sterile peel open packages for one time use only: In this form, matrix is formulated in the form of a sheet, which has to be cut in a size larger than the outline of wound area either in a dry state or in rehydrated state.
  2. Flowable Soft tissue Scaffold: Sometimes, even after surface portion of wound has healed, a remaining tunnel that left treated can lead to breakdown of the wound and formation of new ulcer with easy access to bacteria to cause potentially deep infection. Therefore, this matrix form is made to be applied with a syringe into tunnels or extensions in case of deep wounds.
  3. Bilayer matrix wound dressing: This is a tissue engineered porous matrix of cross-linked bovine tendon collagen and glycosaminoglycan and a semi permeable polysiloxane (silicone) layer. Semi permeable silicone membrane controls water vapor loss, provides a flexible adherent covering for the wound surface and adds tear strength to the device. Moreover, the collagen-glycosaminoglycan biodegradable matrix provides a scaffold for cellular invasion and capillary growth. Wound closure is typically complete within 30 days.

Negative Pressure Wound Therapy

Main article: Negative pressure wound therapy

This treatment uses vacuum to remove excess fluid and cellular waste that usually prolong the inflammatory phase of wound healing. In spite of very straightforward mechanism of action, there are lots of inconsistent results of negative pressure wound therapy studies. Research needs to be carried out to optimize the parameters of pressure intensity, treatment intervals and exact timing to start negative pressure therapy in the course of chronic wound healing.

Application of Growth Factors

This treatment strategy consists of use of growth factors either as one of the components in matrix therapy or via topical application of formulation containing required growth factors. Research shows that growth factors such as epidermal growth factor (EGF), platelet derived growth factor (PDGF), transforming growth factor beta (TGF-8), vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) accelerate tissue repair in an experimental wound model. They attach to cell receptors regulating gene expression of several cytokines and chemokines via different signaling pathways. They promote cell division, migration, angiogenesis and thus start tissue regeneration and remodeling process.