Use of Human Amniotic Membrane in Venous Leg Ulcer Treatment

Introduction

The human amniotic membrane is the innermost collagen-based matrix of the human placenta. Due to its excellent antiadhesive, bacteriostatic, and anti-analgesic (or pain-reducing) properties, it is commonly used as a graft or skin substitute in conditions like venous leg ulcers. In addition, it is usually used as a last resort when the ulcer fails to heal, even after all treatment options are exhausted.

The main advantages of the human amniotic membrane that make it desirable are:

• Easy availability.

• Natural biocompatibility.

• Affordable.

• Low immunogenicity.

• Good mechanical properties (permeability, resorbability, elasticity, and flexibility).

• Good cell adhesion.

• Antifibrotic and pain-relieving effects.

• Source of growth factors, cytokines, and human amniotic membrane cells with stem cell properties.

• The human amniotic membrane is generally considered surgical waste after delivery. So its use raises a few ethical questions.

What Are the Uses of the Human Amniotic Membrane in Regenerative Medicine?

Due to its many advantages, the human amniotic membrane has been widely used in tissue regeneration and biomedical tissue engineering. Some of the common applications of the human amniotic membrane are:

• Treatment of chronic wounds.

• Corneal repair.

• Tendon repair.

• Genital reconstruction.

• Nerve repair.

• Intraoral reconstruction.

• Microvascular reconstruction.

What Are Venous Leg Ulcers?

When the veins in the legs fail to push blood back to the heart, it leads to pressure buildup in the veins. If not treated properly, it can lead to an open sore. This results in venous leg ulcers. It is commonly seen above the ankle of the foot.

The primary cause of venous leg ulcers is high pressure in the veins of the lower leg. Sometimes, the veins' one-way valves that carry blood up to the heart become weak or blocked, which results in a backward flow of blood. As a result, the blood eventually pools in the leg, which is called venous insufficiency.

The major signs and symptoms of venous leg ulcers are:

• Leg swelling and cramping.

• Discolored and hardened skin.

• Itching and tingling.

• Shallow sore with a red base.

• Borders that are uneven.

• Leg pain.

• If infected, there might be a foul smell and discharge.

Various risk factors for venous ulcers include:

• Varicose veins.

• History of blood clots in legs.

• Lymph vessel blockage.

• Old age, tall individuals.

• Family history of venous insufficiency.

• Smoking.

• Pregnancy.

• Obesity.

• Sitting or standing for long periods.

What Are the Treatment Options for Venous Leg Ulcers?

Different treatment options have proven successful in the treatment of venous leg ulcers. The treatment modality varies with the intensity of the condition. Proper assessment and timely intervention are important factors in determining the success of the treatment.

Various treatment options include:

• Dressings: A proper clean dressing should be provided to the patient to prevent cross-infection.

• Topical Ointments: Topical antibiotics are prescribed in cases of infection. Cadexomer iodine, iodine, and mupirocin are commonly used.

• Debridement: Mechanical debridement should be done whenever necessary.

• Systemic Therapy: Systemic antibiotics are used only in cases of confirmed systemic infection. Pentoxifylline is an antibiotic that shows promising results in healing venous leg ulcers.

• Compression Therapy: Multi-layered, adequately padded compression is the standard of care for venous leg ulcers. Compression therapy combined with systemic pentoxifylline has been proven successful in various cases.

• Surgery: People with chronic venous leg ulcers can benefit from surgery because it helps heal wounds.

• Sclerotherapy: Superficial varicosities can be corrected using sclerotherapy. When combined with compression therapy, it yields better results.

How Is the Human Amniotic Membrane Used to Treat Venous Leg Ulcers?

In some cases, even after correcting the underlying conditions, the result would be a non-healing ulcer. In such cases, human amniotic membrane transfer has shown promising results.

Conventionally, skin grafts from other parts were used to cover the wound and aid in healing. But this can only be done a few times and can only be successful in some cases. Furthermore, there is an added burden of wound healing at the donor site, which can again create complications, where the role of the human amniotic membrane comes into play. Human amniotic membrane is similar to skin, and it avoids or minimizes the use of animal collagen, thereby silencing ethical issues. Apart from the amniotic membrane (AM), other skin substitutes like allograft, cultured allograft, de-epidermized (after removal of the epidermal layer) cadaver skin, etc., have been used. But clinical studies have shown that the amniotic membrane is far superior to its counterparts.

Preparation of the amniotic membrane before transplant is done as follows:

• Placentas from patients are collected during a cesarean section after the donor has tested negative for HIV, hepatitis, syphilis, and other diseases.

• In sterile conditions, the amnion is carefully separated from the placenta.

• The amnion (inner) is separated from the chorion (outer) by dissection. It is then cleaned using saline.

• After being treated with gentamicin, the amniotic membrane is put in a collection container. The collection container has 500 ml of sterile saline and heparin.

• After sitting in the container for an hour, the amniotic membrane is put on the wound.

The steps in the application of the amniotic membrane to an ulcer wound are:

• Patient preparation before amniotic membrane transfer

• The patient was briefed on all the risks and complications involved and signed a consent form.

• Wound preparation before amniotic membrane transfer

• A swab of the ulcer surface is taken, and the patient is started on oral antibiotics before the procedure to combat any chance of infection.

• The swab culture results are available in three days. In the meantime, nonviable tissue, eschars, and exudative components are removed.

• Application of the amniotic membrane

• Keeping in mind the size and shape of the wound, the amniotic membrane is cut into different dimensions and applied to the wound.

• The procedure must be done carefully, keeping in mind that no air bubbles should be formed.

• After the total transplant, the wound is carefully dressed. The patient is advised to have strict bed rest for six hours with an elevated foot.

• The entire procedure should be carried out in a sterile environment.

What Are the Risks And Complications?

Risks and complications involved in human amniotic membrane grafting for venous leg ulcers are minimal. Almost 100 percent of patient satisfaction and success are usually reported with this treatment. Even though it is an allograft transfer, reports of allergy or immune reactions have been rare.

Conclusion

With emerging shards of evidence from studies worldwide, the human amniotic membrane has gained widespread acceptance as a treatment for non-healing venous ulcers. Not only is this an effective treatment option but also cost-effective, making it accessible to all sections of the population.