This author discusses how the use of an innovative human amniotic membrane graft enhanced healing in three patients with lower extremity wounds. Homologous tissue in wound healing has been in use for many years and recently human amnion-derived materials have become available to clinicians. Amniotic membrane derived allografts that consist of a dehydrated composite of amniotic and chorionic membranes are particularly interesting as they combine layers of the amniotic membrane that are both subjects of intensive research. These membranes are isolated from donor placentas and then have minimal processing in order to cleanse and disinfect tissue. The disinfection process is designed to maintain the structural properties and composition of the extracellular matrix, and preserve the inherent sensitive biomaterial components. One can use such carefully isolated human allografts as temporary covers for wounds until they progress to epithelialization and closure. The following case studies demonstrate the use of a placental tissue, Revitalon Amniotic Membrane (Medline Industries). This tissue is unique in that it is processed aseptically and contains both the amnion and chorion components of the amniotic membrane. I chose difficult to heal wounds on the lower extremity for this case report. It is important to note that the presence of severe vascular compromise, active or latent infection, or uncontrolled infection at the wound site may compromise the usefulness of the tissue. I chose and managed the following three patients with single or repeated applications of a human amniotic membrane (Revitalon) allograft. Wound bed preparation was the same in all cases. I performed tangential en bloc debridement of a full-thickness nature with excision of all non-viable tissue to a healthy bleeding wound bed to get the wound bed ready for the application of amniotic membrane.
Case Study One: Treating An Open Wound At The First MPJ
A 75-year-old female initially presented on July 9, 2013 in the hospital for consultation for possible debridement of an open wound to the right great toe joint. An orthopedic surgeon initially saw her on July 6 and performed a bedside I&D and packed the wound with ORC collagen. The patient’s past medical history is pertinent for chemotherapy for acute myeloid leukemia, type 2 diabetes, coronary artery disease, hypertension and gout. She had been taking colchicine (Colcrys, Takeda Pharmaceuticals), acetaminophen/codeine (Tylenol #3, McNeil Consumer Healthcare), glipizide (Glucotrol, Pfizer), NovoLog (Novo Nordisk) per a sliding scale, lisinopril (Prinivil, Merck) and methylprednisolone (Solu-Medrol, Pfizer). She had no allergies and did not smoke or drink. The wound initially measured 2.0 cm x 2.5 cm x 0.2 cm and was dorsal to the first metatarsophalangeal joint (MPJ) on the right foot. Cellulitis was present with slough to the wound bed. Pulses were palpable +2/4 bilaterally. There was no focal defect loss. Distal symmetric loss of protective sensation was present bilaterally. I performed wound debridement on July 12. Negative pressure wound therapy initiated in-hospital. She had a normal postoperative course after debridement with primary closure. I sent the patient to a skilled rehab facility for postoperative management. I saw the patient for follow-up on Aug. 1 and 7. During the post-hospital course, her wound became contaminated and further infected. I performed excisional debridement and restarted negative pressure therapy. I discharged the patient to rehab in a skilled nursing facility where her wound remained non-healing secondary to her advancing acute myelodysplastic leukemia. The patient was unable to be medically cleared for additional surgery to close the wound and was discharged from rehabilitation on Aug. 14. Due to the nature of the wound dehiscence and patient morbidity, I discussed amniotic tissue application with the patient at length. The wound size at this time was 1.0 cm x 1.0 cm x 0.1 cm. After thoroughly preparing the wound bed, I applied Revitalon amniotic tissue to the wound on August 23 and used normal saline to hydrate the tissue upon placement. After using a non-adherent contact layer on the wound site to cover the Revitalon, I employed a secondary dressing of 4x4 gauze, Kling and self-adherent wrap. The patient went on to heal at day 14 post-application without complications..
Case Study Two: Treating A Non-Healing Wound After Mohs Surgery
A 78-year-old male received a referral for a non-healing ulceration following Mohs micrographic surgery to the dorsum of the right foot on Nov. 18, 2013. The patient’s past medical history was pertinent for chronic, stage V kidney disease. He was on peritoneal dialysis and anticoagulant therapy. The patient had an abnormal gait, type 2 diabetes and peripheral arterial disease (PAD). His previous treatments consisted of mupirocin ointment for two weeks, a silver alginate/hydrofiber dressing for one week and failed ORC collagen for three weeks. I applied Revitalon at week two after preparation of the site via full-thickness tangential debridement. He had the standard dressing protocol and presented weekly for dressing changes. Dressings consisted of Adaptic 4x4 and Kerlix. The wound completely resolved at day 63 post-application.
Case Study Three: Resolving A Laceration Injury
An 85-year-old female presented with a laceration injury to her anterior right leg after six weeks of non-healing. The patient’s past medical history was pertinent for PAD, atrial fibrillation and anticoagulant therapy. She had an abnormal gait, diabetic peripheral neuropathy and dementia. Her previous treatments consisted of systemic antibiotics, topical enzymatic debridement and platelet-derived growth factor wound gel. She refused compression therapy and surgical debridement techniques. I applied Revitalon at the first visit on May 14, 2014. She received a standard wound dressing with a non-adherent contact layer, 4x4 and Kling. I removed the dressing after one week. The patient presented two weeks after Revitalon application with a fully epithelialized wound. The wound continued to heal for an additional two weeks but never re-opened or had further exudate.
In examining the use of amniotic membrane allografts (Revitalon) on patients with chronic venous ulcers, previous studies have yielded positive results.1-3 Results from this case study evaluation are in the table “Assessing The Decrease In Wound Volume After Revitalon Application” below at the left. This table describes the reduction in wound volume over time. The reporting of wound volume over time is a metric that takes wound size or area into account along with wound depth. Patients with wounds associated with surgery, diabetes and peripheral arterial disease were part of this case series. After the application of Revitalon, the wounds progressed to healing and wound closure. The use of this amniotic membrane allograft may yield future results with wound healing that would need to be more thoroughly investigated via randomized controlled trials. Dr. Lullove is in private practice in Boca Raton and Delray Beach, Fla. He is a Staff Physician at West Boca Medical Center in Boca Raton. Dr. Lullove is a Fellow of the American College of Certified Wound Specialists. References 1. Bennett J, Matthews R, Faulk WP. Treatment of chronic ulceration of the legs with human amnion. Lancet. 1980;315(8179):1153–6. 2. Ward DJ, Bennett JP, Burgos H, Fabre J. The healing of chronic venous leg ulcers with prepared human amnion. Br J Plast Surg. 1989;42(4):463-7. 3. Sommerville PG. The possible use of amniotic membrane in chronic leg ulcers. Phlebologie. 1982;35(1):223-9. Additional References 4. Faulk WP, Matthews R, Stevens PJ, et al. Human amnion as an adjunct in wound healing. Lancet. 1980;1(8179):1156-8. 5. Troensegaard-Hansen E. Amniotic grafts in chronic skin ulceration. Lancet. 1950;255(6610):859-60. 6. Von Versen-Hoeynick F, Syring C, Bachmann S, Moller DE. The influence of different preservation and sterilisation steps on the histological properties of amnion allografts – light and scanning electron microscopic studies. Cell Tiss Bank. 2004;5(1):45–56. 7. Von Versen-Hoeynck F, Steinfeld AP, Becker J, et al. Sterilization and preservation influence the biophysical properties of human amnion grafts. Biologicals. 2008;36(4):248-255. 8. Bose B, Ann R. Burn wound dressing with human amniotic membrane. Coll Surg Engl. 1979; 61(6):444–7. 9. Quinby WC Jr., Hoover HC, Scheflan M, et al. Clinical trials of amniotic membranes in burn wound care. Plast Reconstr Surg. 1982;70:711–6. 10. Sawhney CP. Amniotic membrane as a biological dressing in the management of burns, Burns.M 1989;15(5):339–42. 11. Wang L, Wu X, Shi T, Lu L. Epidermal growth factor (EGF)-induced corneal epithelial wound healing through nuclear factor κB subtype-regulated CCCTC binding factor (CTCF) activation. J Biol Chem. 2013; 288(34):24363-71. 12. Schneider L, Cammer M, Lehman J, et al. Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts. Cell Physiol Biochem. 2010; 25(2-3):279–2. 13. Jiang B, Zhang G, Brey EM. Dual delivery of chlorhexidine and platelet-derived growth factor-BB for enhanced wound healing and infection control. Acta Biomater. 2013;9(2):4976-84. 14. Niknejad H, Peirovi H, Jorjani M, et al. Properties of the amniotic membrane for potential use in tissue engineering. Eur Cell Mater. 2008;15:88-99. 15. Hampson V, Liu D, Billett E, Kirk S. Amniotic membrane collagen content and type distribution in women with preterm premature rupture of the membranes in pregnancy. Br J Obstet Gynaecol. 1997;104(9):1087-91. 16. Fukuda K, Chikama T, Nakamura M, Nishida T. Differential distribution of subchains of the basement membrane components type IV collagen and laminin among the amniotic membrane, cornea, and conjunctiva. Cornea. 1999;18(1):73-9. 17. Meinert M, Eriksen GV, Peterssen AC, et al. Proteoglycans and hyaluronan in human fetal membranes. Am J Obstet Gynecol. 2001;184(4):679-85. 18. Kuo HJ, Maslen CL, Keene DR, Glanville RW. VI collagen anchors endothelial basement membranes by interacting with type IV collagen. J Biol Chem. 1997;272(42):26522-9.