Surgeons share how they evaluate whether a wound bed is ready for either an acellular dermal matrix or a skin graft
MIT professor Ioannis Yannas, Ph.D., remembers the day — almost 50 years ago — that Dr. John Burke gave him a tour of the pediatric ward at the Shriners Burn Institute at Mass General Hospital in Boston. “I was shocked beyond belief,” he says about the sight of children with extensive bandages on their faces and limbs in the above Emmy-award winning video Hope Regenerated. “There was a great deal of human misery that was confronting me, and I felt I had to do something about it.”
Although Burke, chief of staff at Shriners, had already made significant strides in burn treatment, patients with full thickness burns still faced death due to infection and dehydration. In order to achieve better patient outcomes, Burke wanted a bandage that would keep moisture in and bacteria out, but more importantly, one that would speed up the wound closure for severely burned patients. Yannas, who was researching the physics of collagen and the theory of viscoelasticity in polymers, thought he could help.
Yannas and his students began to create polymers from different chemical families — plastics, rubbers, textile fibers and body tissues. They tested these new dressings at Shriners’ animal lab facility, but none of them sped up how quickly the burn wounds closed.
Then Yannas decided to try collagen. Not only did the collagen not speed up wound closure, he says it actually slowed closure. The experiment had failed — nothing seemed to make the wound close more quickly.
But when Yannas and Burke looked at why the experiment failed, they discovered that the animals treated with collagen dressings were not making scar tissue as every other animal before that had done. “[It] was actually causing new skin to be formed instead of scar,” Yannas says in the video. “Skin that functions like skin as opposed to scar that does not function like skin.”
Yannas and Burke’s success was announced on the front page of the New York Times on April 24, 1981. The product they created was a combination of a protective silicone outer sheet over a scaffolding of cow tendon and shark cartilage that would not be rejected by the body’s immune system. At the time of the announcement, the product had been used experimentally on 19 severely burned patients, including one patient with burns over more than half of her body.
Initially known as “artificial skin,” Burke and Yannas’s invention was the founding product of Integra LifeSciences and is now called Integra Dermal Regeneration Template (IDRT). It was the first product approved by the FDA with a claim of regeneration of dermal tissue.
Artificial skin was developed at a critical time. In the 1970s, there were significant advances in ICU care that helped keep severe burn victims alive longer, but patients were still at risk because they often lacked sufficient donor sites. Yannas and Burke’s invention helped make the practice of early excision and grafting a universally accepted treatment of severe burns.
Today, IDRT remains the only FDA-approved regenerative skin technology for the treatment of life-threatening burns, and its indications not only include third-degree burns, but also scar revisions and chronic diabetic wounds. It is approved in more than 50 countries outside the U.S., including the U.K., Germany, Canada, Australia, Brazil, and Japan.
Burke, who passed away in 2011, and Yannas were inducted into the National Investors Hall of Fame in 2015, alongside luminaries including Steve Jobs, Louis Pasteur and the Wright Brothers.
Please read below for more information about Integra Dermal Regeneration Template:
Integra template is indicated for the postexcisional treatment of life-threatening full-thickness or deep partial-thickness thermal injuries where sufficient autograft is not available at the time of excision or not desirable due to the physiological condition of the patient. Integra template is also indicated for the repair of scar contractures when other therapies have failed or when donor sites for repair are not sufficient or desirable due to the physiological condition of the patient.
Integra template is also marketed as Integra® Omnigraft™ Dermal Regeneration Matrix. Omnigraft is indicated for the use in the treatment of partial and full-thickness neuropathic diabetic foot ulcers that are greater than six weeks in duration, with no capsule, tendon or bone exposed, when used in conjunction with standard diabetic care.
Use of Integra template is contraindicated in patients with known hypersensitivity to bovine collagen or chondroitin materials. Integra template should not be used on clinically diagnosed infected wounds.
Warnings and Precautions
Excision of the wound must be performed thoroughly to remove all coagulation eschar and nonviable tissue. Integra template will not “take” to nonviable tissue. Leaving any remaining nonviable tissue may create an environment for bacterial growth.
Hemostasis must be achieved prior to applying Integra template. Inadequate control of bleeding will interfere with the incorporation of Integra template.
There have been no clinical studies evaluating Integra template in pregnant women. Caution should be exercised before using Integra template in pregnant women. Such use should occur only when the anticipated benefit clearly outweighs the risk.
In clinical trials, the use of Integra template was evaluated in a small number of patients with chemical, radiation, or electrical burns. A surgeon’s decision to use Integra template on these wounds should be based on their evaluation of the wound and its suitability to excisional therapy, the likelihood that a viable wound bed will be created by excision, and whether the possible benefit outweighs the risk in this patient population.
The extent of scarring associated with the use of this product has not been determined.
Integra template has been found to be well tolerated in 4 prospective clinical trials involving 444 burn patients. There were no reports of clinically significant immunological or histological responses to the implantation of Integra template. There were no reports of rejection of Integra template.
Adverse events reported in the Integra template clinical trials include death, sepsis, apnea, heart arrest, pneumonia, kidney failure, multisystem failure, and respiratory distress. With the exception of wound fluid accumulation, positive wound cultures, and clinical wound infection, none were directly related to the use of Integra template.
In these clinical trials, data were collected regarding wound infection. The consequences of infection at sites treated with Integra template included partial or complete loss of take (incorporation into the wound bed) of Integra template. Infection rates in sites treated with Integra template in these three clinical trials supporting the PMA ranged from 14 to 55%. The overall infection rate for the Postapproval Study was 16.3%.
Adverse events in the Postapproval study were similar to those observed in the previous clinical trials and are common in populations of critically ill burn patients regardless of type of treatment used.
There were no trends noted. There were six adverse events which were rated by the investigator as being related. These events were all single occurrences except for sepsis (2). These adverse events occurring in <1% of the safety population.
Incidence of adverse events occurring in >1% of the safety population in the Post-approval Study are as follows: Sepsis (23.1%), Death (13.9%), Infection (2.8%), Thrombophlebitis (2.8%), Kidney Failure (2.8%), Necrosis (2.3%), Hemorrhage (2.3%), Heart Arrest (1.9%), Apnea (1.9%), Pneumonia (1.9%), Allergic Reaction (1.4%), Fever (1.4%), Multisystem Failure (1.4%), Atrial Fibrillation (1.4%), Gastrointestinal Hemorrhage (1.4%), Kidney Abnormal Function (1.4%).
Contracture Release Patients
The following adverse events were reported in a Reconstructive Surgery Study involving 20 patients with 30 anatomical sites and a Retrospective Reconstruction Contracture Survey involving 89 patients and 127 anatomic sites.
Incidence of adverse events in the Reconstructive Contracture Surgery Study and Retrospective Contracture Reconstruction Survey are as follows: Infection (0.0%), Fluid under Silicone Layer (0.0%), Partial graft loss (Integra) (0.0%), Failure to take (Integra) (0.0%), Shearing/Mechanical shift (3.3%), Hematoma (16.7%), Granulation tissue formation (0.0%), Delayed Healing (0.0%), Separation of the Silicone Layer (0.0%), Seroma (0.0%), Pruritis (0.0%), Epidermal autograft loss >15% (6.7%), Epidermal autograft loss <15% (23.3).
There were no infections reported in the Reconstructive Surgery Study and the reported infection rate was 20.5% in the Retrospective Contracture Reconstruction Survey. No deaths were reported.
Diabetic Foot Ulcer Patients
All adverse events that were reported in the study evaluating Omnigraft for the treatment of diabetic foot ulcers at a frequency of ≥ 1% in either cohort are presented in Table 1 in the Instructions for Use.
The most common adverse events experienced by patients treated with Omnigraft were: wound infection (15%); new, worsening, or recurring wounds (14%); pain around the wound (9%); infection beyond the wound (either cellulitis or osteomyelitis, 14%); swelling (5%); nausea (5%); worsening health condition (4%). These adverse events occurred in a similar or lower percentage of patients treated with Omnigraft compared to patients treated with standard wound care alone.
The sale of Integra template is restricted to clinicians who have completed a company sponsored training program. Product training is available at ilstraining.com.