Amniotic Membrane: Can It Have An Impact For DFUs?

Author(s): 
Jennifer Swan, DPM, and Christopher Hyer, DPM, FACFAS

A Guide To The Unique Properties Of Amniotic Membrane

Amniotic membrane is placental tissue that comes from donated placenta after childbirth. It consists of the innermost layer of tissue that is comprised of a thin epithelial layer, a thick basement membrane and an avascular stroma.2

   There are several unique properties of amniotic membrane that make it ideal for wound healing.
• Amniotic membrane has abundant stem cells that one can harvest without moral and ethical concerns.
• Amniotic membrane lacks immunogenicity via a low expression or lack of expression of histocompatibility antigens.
• Amniotic membrane has the ability to produce healing with little to no scarring. Along with the indirect contribution of amniotic membrane’s anti-inflammatory effects, there has been evidence of direct reduction of scarring. Tseng and colleagues demonstrated in a laboratory study that there was a direct anti-scarring action on ocular surface fibroblasts by suppressing transforming growth factor beta (TGF-b).3 The TGF-b is responsible for activation of fibroblasts and by down-regulating this process, there is a reduction and prevention of adhesion and fibrosis.
• Amniotic membrane has the ability to impart anti-inflammatory effects by mediating pro-inflammatory cytokines such as interleukin (IL-6) and TNF-alpha. Tseng and colleagues noted that enzyme-linked immunosorbent assay (ELISA) extracts have high levels of IL-10, which counteracts inflammatory effects.3 In addition, they have found amniotic membrane down-regulates the expression and production of IL-1, and up-regulates interleukin-1 receptor antagonist (IL-1RA).

   Given all these properties of amniotic membrane, one can imagine what a great benefit it is to have this type of product available to heal these ever challenging diabetic wounds.

Examining The Different Processes For Preserving Amniotic Tissue

Currently, there are two methods of preserving amniotic tissue, dehydration (Purion, MiMedx) and cryopreservation (CryoTek, Bio-Tissue/Amniox Medical).

   The Purion method uses a series of rinsing the amniotic tissue in hypertonic salt solutions and dehydration under elevated temperatures. The concern with this type of processing is that it can lead to the destruction of the very elements of the amniotic membrane that are integral in healing.

   The new CryoTek process claims to maintain the structures of amniotic membrane. A recent study not yet published by Tan and coworkers demonstrated histologically that the CryoTek process preserved the extracellular matrix and structural proteins of amniotic membrane.4 However, when evaluating the dehydration method results, the study researchers found the morphology of the tissue was compacted, which implies structural changes to the matrix. In addition, both processes demonstrated the presence of hyaluronan.

   Liu and coworkers demonstrated that hyaluronan in amniotic tissue is present in the form of a heavy chain of inter-alpha-inhibitor-hyaluronan (HC-HA) complex. The authors believe this complex plays a role in anti-angiogenic activity as well as stabilizing the extracellular matrix.4,5 Results of the study via western blot analysis demonstrated high levels of HC-HA using the CryoTek process. The dehydrated process had the presence of HC-HA but it was minimal or with an altered band appearance. Accordingly, it certainly appears that the way the tissue is processed also makes a difference in maintaining the integrity of the amniotic membrane.

Comments

I have an end-stage renal patient with poor blood flow, calcified vessels etc. Her wound is over the bunion joint 3 cm x 2.5 cm and channels 2 inches under the first met head. Can I pack the graft into the dead space and use a second graft over the ulcer ?

Dr. Aufseeser:

I think in your patient's case, you would get better results by using an injectable amniotic implant. This is infiltrated around and under the ulcer, usually in a series of 2 or 3 every other week. In my experience, this promotes vascular neogenesis and then wound healing. It doens't happen overnight but I usually see a dramatic change at week 3 or 4.

The injectables seem to all be similar in action despite what their manufacturers say. My personal favorite seems to be Flograft but I'll use whatever my institution has on hand.

Dave Gottlieb, DPM
Baltimore

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