Exploring The Potential Of Advanced Wound Care Products For Diabetic Wounds

Author(s): 
E. Giannin Perez, DPM, MS, and Khurram H. Khan, DPM, FACFAS

   Dermoinductive products derive from living cell cultures containing human living keratinocytes, fibroblasts or both. These products recruit and activate tissue within the wound bed. Products include Apligraf (Organogenesis), Dermagraft (Shire Regenerative Medicine), Epicel (Genzyme) and Laserskin/Vivoderm (Fida Advanced Biopolymers). Apligraf and Dermagraft are FDA-approved for diabetic foot ulcers.

   Dermoconductive products do not contain living cells and serve as a scaffold matrix allowing the infiltration of cells in an organized fashion. Products include Integra (Integra Life Sciences), Oasis (Smith and Nephew), Graftjacket (KCI), GammaGraft (Promethean LifeSciences), EZ-Derm (Molnlycke Health Care), Alloderm (LifeCell), Biobrane (Smith and Nephew), TransCyte (Smith and Nephew), Primatrix (TEI Biosciences) and MatriStem (Acell). Oasis and MatriStem are FDA approved for diabetic foot ulcers.

How Human Amniotic Membrane Is Emerging As A Viable Treatment

Recently, much attention has focused on human amniotic membrane for the treatment of chronic wounds. However, researchers have actually used human amniotic membrane for wound care treatment since the early 1900s. In 1910, Davis published a review of cases from Johns Hopkins Hospital.9 In 1913, Stern reported on amniotic membranes to treat ulcerated skin surfaces due to burns and Sabella used fetal membranes in skin grafting.10,11 Human amniotic membrane is currently in use in the field of ophthalmology promoting corneal epithelialization but has also been in use for burn injuries and ulcers, mandibular vestibuloplasty, dural defect repair, intra-abdominal surgery and gynecological reconstructive surgery.12

   Amniotic membrane is the innermost layer of the placenta. Amniotic membrane is composed of a thin epithelial layer, a thick basement membrane and avascular stroma.

   In 1979, Trelford and colleagues found that amniotic fluid promoted epithelial healing, reduced inflammation, increased comfort and decreased the severity of insufficient vascularization.13 In 2004, Zhang and coworkers noted that mesenchymal stem cells in human placenta are able to differentiate into osteogenic, adipogenic and chondrogenic lineages and demonstrated an ability to suppress T-cell proliferation.14 Solomon and colleagues in 2005 showed that amniotic membrane transplantation promotes re-epithelialization, decreases inflammation and fibrosis, and modulates angiogenesis.15

   Amniotic membrane (or amnion) is therefore of particular interest because it can provide cells with multipotency. One can easily obtain amnion from the human placenta after a Caesarean section and the controversies that surround human embryonic stem cells do not apply in the procurement of amniotic membranes since placentas are discarded after childbirth. Serological testing occurs prior to C-sections and with the mother’s/donor’s consent.

   Amniotic membrane contains amnion epithelial cells derived from embryonic ectoderm and amnion mesenchymal cells derived from embryonic mesoderm. Amnion and mesenchymal cells lack immunogenicity as the placenta is an organ that is immune privileged and therefore can be part of any immunocompromised patient either from human immunodeficiency virus or post-transplant.15

   Amniotic membrane comes in two forms: dehydrated human amniotic membrane and cryopreserved human amniotic membrane. Dehydrated human amniotic membrane is pliable at room temperature, has a shelf life of five years, comes in different sizes and contains chorion, a part of the membrane that separates the fetus from the placenta. The cryopreserved form has a two-year shelf life and does not contain chorion. To date, there is no research available on the benefits or disadvantages to having chorion in the amniotic membrane.

   However, with the graft form of amniotic membrane, controversy exists as to which side should face the wound, the amniotic or chorionic side. In a study of sheep, Trelford and colleagues showed an immunological response when the chorionic side faced the wound.16 Such a response suggested maternal decidual fragments may inadvertently accompany the chorion. Robson and coworkers studied “vascular invasion” and recommended not separating the chorionic surface from the amnion in order to see vascularization.17

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