Human Umbilical Cord & Amniotic Membrane Reduces Pain, Augments Healing of Acute Trauma Wounds

For orthopedic trauma surgeons in community hospitals, it can be challenging to convince plastic surgeons in private practice to close traumatic wounds with skin grafts, free flaps, or other reconstructive interventions. Many of these trauma patients are at high risk for acute and chronic wound complications because they live with comorbidities such as diabetes or peripheral vascular disease (PVD), are smokers or drug users, and/or are obese. These patients also often present with large traumatic wounds that have higher failure rates than nontraumatic wounds. Private-practice plastic surgeons, cognizant that wound complications account for up to 20% of malpractice lawsuits, generally aren’t eager to treat this population.^1,2 Out of necessity to provide acute and definitive soft tissue coverage, today’s wound care providers and surgeons have at least one other option for this population: cryopreserved human umbilical cord and amniotic membrane (UC/AM) for traumatic wounds. These tissues possess unique anti-inflammatory, anti-scarring properties that have led to their therapeutic use for chronic wounds.^3-5 They have also proven effective when utilized as part of a comprehensive wound care regimen when collaborating with the outpatient clinic. This article will discuss the properties and indications of UC/AM and offer a case study of an older-adult male who required outpatient treatment. 

UMBILICAL CORD & AMNIOTIC MEMBRANE SPECIFICATIONS

UC/AM has been known to heal wounds without scarring in a regenerative process. Heavy chain hyaluronic acid/pentraxin-3 is the key protein complex present in these tissues, which are also rich in collagen, fibronectin, and growth factors. There are two types of macrophages in the bioactive tissues that regulate inflammation and prevent scar formation — an inflammatory phenotype and a pro-healing phenotype. The inflammatory macrophages cause apoptosis, which repopulates and multiples the number of pro-healing macrophages. UC/AM placed in the wound bed acutely jumpstarts healing and reduces the inflammatory response, which results in less scarring, pain, and swelling. By improving bone and soft tissue healing and preventing contractures, UC/AM decreases postoperative trauma wound complications, reoperation, and readmission rates. Unlike a skin graft that adheres only to muscle or fascia, UC/AM can be used to cover bone, tendon, and hardware.  

In a study of open tibia fractures, two criteria were crucial to reducing infection rates: administering antibiotics within 66 minutes of the injury and covering soft tissue defects within five days.⁶ If both criteria were met, the wound infection rate was 2.8%. Missing one criterion caused the infection rate to rise to 10%. Skipping both caused the infection rate to soar to 40%. For clinicians who administer antibiotics early, and now with UC/AM, the immediate placement of a graft can be conducted to cover the wound after debridement and stabilization of the soft tissue. The products — NEOX^® Wound Allograft, CLARIX^® Regenerative Matrix, and FLO Particulate Matrix (Amniox Medical^® Inc.,  Atlanta, GA) — are cryopreserved and available for use within minutes. UC/AM contains no live cells, which eliminates concerns related to allergy and graft-versus-host reaction from the tissues or from transmission of a pathogen such as HIV or hepatitis C. The NEOX allograft is available in multiple sizes, and most patients require only one graft (in the experiences of this author). Occasionally, a vacuum dressing may be needed to provide negative pressure wound therapy for 1-2 weeks after graft placement. (In the experiences of this author, the majority of patients seem to do well with a moist dressing placed over the graft, which can be conducted in the home.)

Regarding traumatic wounds, the UC/AM graft demonstrated dramatic effect for one patient who experienced an open forearm fracture and received grafting on the volar aspect of the soft tissue defect and a split-thickness skin graft on the dorsal aspect of the defect. The regular skin graft healed as expected — without scarring, no skin sensation, and no hair regrowth. The graft successfully regenerated the tissue, returning sensation and hair to the skin with no scarring. The UC/AM graft has also shown effectiveness (in the experiences of this author) in wounds that achieved closure without grafting, but for which there was anticipated compromised healing due to a patient’s comorbidities, when placed in the soft tissue under the skin to prevent wound breakdown. In the event of wound breakdown, the graft provides a covering over the bone and hardware that enables the wound to be treated with basic care, presumably while avoiding a return trip to the operating room (OR). For potentially problematic wounds, an injection of UC/AM particulate matrix along the incision line has been known to accelerate healing (in the experiences of this author) with less wound gapping, drainage, and swelling. For articular fractures, an injection of UC/AM particulate matrix into the joint can help provide nourishment and prevent swelling and scarring that limit range of motion. Studies show that moving the joint early after an articular fracture preserves more of the cartilage and prevents post-traumatic arthritis. By promoting healing, UC/AM allows patients to move their joints sooner and with less pain.

LOWER COMPLICATION RATES

A study of 33 patients with complicated open and closed fractures who received UC/AM as an adjunctive wound therapy has been conducted.⁷ Comorbidities for these patients included osteomyelitis (66%), nicotine dependence (43%), PVD (40%), alcohol and/or drug abuse/dependence (57%), diabetes (17%), and congestive heart failure (10%). The average age was 47.5 years, and average body mass index was 28.1. Over the course of seven months, only 7% of patients required reoperation or readmission for wound complications, and only 10% required reoperation for infection. None of the patients required a plastic surgeon to close their wounds. Preliminary data from a current retrospective study of open reduction and internal fixation of calcaneal fractures in 46 patients also show a dramatic reduction in wound complication rates in patients who received UC/AM adjunctive wound therapy compared with those who received standard wound care. Most calcaneal fractures occur in men ages 45-65 who fall off a ladder and strike their heels at high velocity. Historically, 25% of this author’s patients with operatively treated calcaneal fractures require wound care, antibiotics, or a return to the OR for a deep-seated infection after open reduction and internal fixation of the fracture. All patients were seen at three weeks, six weeks, 12 weeks, and six months postoperatively. Among the patients who received UC/AM grafting, the overall complication rate was 15%. The readmission and reoperation rate was reduced to 5% in patients who received a UC/AM graft compared with 10% among patients who received standard wound care. Besides producing better outcomes for patients, UC/AM wound treatment administered during surgical fracture fixation is more cost-effective than having the patient return to the OR days later for reconstructive plastic surgery (in the experiences of this author). 

CASE STUDY

“Ed,” 66, smokes nearly two packs of cigarettes per day, lives with PVD, and abuses methamphetamines. Ed was high on meth when he crashed his motorcycle in 2016, the result of which included an open tibia/fibular fracture with a vascular injury and a large soft tissue defect. His tibia was surgically repaired, and fasciotomies were conducted for relief of reperfusion compartment syndrome. His wound was covered with a split-thickness skin graft approximately 8 cm x 28 cm, which broke down completely with more necrotic tissue while Ed was undergoing rehabilitation. Ed was now dealing with exposed bone, tendon, and hardware. He returned to the OR two times for outpatient debridement, and the wounds were placed in NEOX grafts. He was discharged after surgery and conducted his own wound care. Within two months, his wounds were stable and improving, and he was ambulating with only a mild limp. The wounds took approximately six months to heal, followed by full soft tissue and bone healing. Ed was discharged from ongoing outpatient clinic visits one year post-injury. 

Christopher M. Stewart is director of orthopaedic trauma at Baptist Health Medical Center, Little Rock, AR. He reports no financial conflicts of interest.

References 

1. Karcz A, Korn R, Burke MC, et al. Malpractice claims against emergency physicians in massachusetts: 1975-1993. Am J Emerg Med. 1996;14(4):341-5.

2. Henry GL, Sullivan DJ. Emergency Medicine Risk Management: A Comprehensive Review. 2nd ed. Irving, TX. American College of Emergency Physicians; 1997.

3. He H, Li W, Tseng DY, et al. Biochemical characterization and function of complexes formed by hyaluronan and the heavy chains of inter-α-inhibitor (HC-HA) purified from extracts of human amniotic membrane. J Biol Chem. 2009;284(30):20136-46.

4. Zhang S, He H, Day A, Tseng SC. Constitutive expression of inter-α-inhibitor (IαI) family proteins and tumor necrosis factor-stimulated gene-6 (TSG-6) by human amniotic membrane epithelial and stromal cells supporting formation of the heavy chain-hyaluronan (HC-HA) complex. J Biol Chem. 2012;287(15):12433-4.

5. He H, Zhang S, Tighe S, Son J, Tseng SC. Immobilized heavy chain-hyaluronic acid polarizes lipopolysaccharide-activated macrophages toward M2 phenotype. J Biol Chem. 2013;288(36): 25792-803.

6. Lack WD, Karunakar MA, Angerame MR, et al. Type III open tibia fractures: immediate antibiotic prophylaxis minimizes infection. J Ortho Trauma. 2015;29(1):1-6.

7. Stewart C, Griffin, K. Cryopreserved umbilical cord (cUC) use for acute orthopedic trauma wounds. Poster presented at SAWC Spring, San Diego, CA, April 5-9, 2017.