FDA Approved Indications:
Apligraf is indicated for use along with standard compression therapy in the treatment of venous ulcers of at least 1 month in duration that have not adequately responded to conventional ulcer therapy. The bi-layered living skin equivalent is also indicated for for the treatment of full-thickness neuropathic diabetic foot ulcers of greater than three weeks duration, which extend through the dermis but without tendon, muscle, capsule or bone exposure.
These ulcers occur as a direct consequence of a patient exhibiting venous disease of the leg. Venous ulcers also arise in a subset of those members of the population with varicose veins and chronic venous insufficiency (CVI). Nearly 7 million people in the United States suffer from chronic venous insufficiency, which can progress to venous leg ulceration. CVI arises from a variety of causes including deep vein thrombosis and same vein valve incompetence. The condition leads to venous hypertension, accumulation of fluid in pen-capillary tissues of the lower limb and diverse symptoms such as swelling, night cramps and paraesthesia. The unfortunate end consequence of these processes is a venous ulcer of the leg. According to Dr. Glenn Davis, a plastic surgeon at Rex Healthcare, "such wounds often appear resistant to healing, produce copious amounts of exudate and require regular dressing changes." It is well documented that compression therapy utilizing bandages that give a graduated pressure from heel to knee is essential for healing to occur. Even with compression therapy, complete healing may take many weeks or months.
For more information regarding venous leg ulcers and its pathophysiology, clinical features, and clinical management, please view this website: http://www.apligraf.com/content/woundfact_woundove r_aboutvlu.htm
ulcers are a common complication for many patients suffering from
diabetes. More hospital beds are occupied by patients with foot ulceration, than
all other complications of diabetics combined. Diabetic foot ulceration is
frequently the cause of amputation, and in some cases can prove life threatening
due to infection or gangrene. Following ulceration, the incidence of amputation
is 15 times higher in people with diabetes than non-diabetic individuals. Of
those diabetic patients suffering from foot ulcers, approximately 10% require
amputation. Two predisposing features contribute to the high incidence of
amputation, namely - neuropathy and ischemia, both of which can lead to localized
tissue trauma, subsequent breakdown, necrosis and infection. Diabetes
itself is and increasing problem in all developed countries, and the incidence
of diabetic ulcers is increasing on an annual basis. The incidence of diabetic
ulcers per year is estimated at 800,000 in the United States. An effective
treatment able to induce or augment tissue repair in non-healing wounds would
contribute greatly to reducing complications, and improving quality of life in
patients with diabetic ulcers and other dermal lesions.
For more information regarding diabetic foot ulcers, please view this website: http://www.apligraf.com/content/woundfact_woundove r_aboutdfu.htm
In the United States alone, there
are 100,000 hospital-treated burns per year and 600,000 cases of surgical skin
excision, together costing an estimated $70 million per year. In
light of the need for new biological agents for obtaining wound closure in burn
patients, a trial evaluating the effectiveness of meshed Apligraf in burn
patients was conducted
(Waymack, Duff, et. al. Burn 26 (7): 2000. pp609-619). The objective of
this trial was to determine the safety and effectiveness of Apligraf for
providing overlay coverage of widely meshed autograft. Experimental treatment
sites had Apligraf placed over meshed autograft while control sites were treated
with meshed autograft covered with meshed allograft, or meshed autograft not
covered by a biologic dressing. Forty patients were entered into this study of
which 38 were evaluated. At the completion of the study 58% of the Apligraf
sites were rated superior to the control sites by the investigators, 26% were
rated equivalent to the control and 16% were rated worse than control (p=0.0037).
In the Apligraf group, pigmentation was significantly better than control and by
month 24, (45% Apligraf sites had normal pigmentation compared with 13% of
control sites (p=0.0005). Similarly, by month 24, 47% of patients had
normal vascularity at the Apligraf site compared with 16% of patients at the
(Waymack, Duff, et. al. Burn 26 (7): 2000. pp609-619). The objective of this trial was to determine the safety and effectiveness of Apligraf for providing overlay coverage of widely meshed autograft. Experimental treatment sites had Apligraf placed over meshed autograft while control sites were treated with meshed autograft covered with meshed allograft, or meshed autograft not covered by a biologic dressing. Forty patients were entered into this study of which 38 were evaluated. At the completion of the study 58% of the Apligraf sites were rated superior to the control sites by the investigators, 26% were rated equivalent to the control and 16% were rated worse than control (p=0.0037). In the Apligraf group, pigmentation was significantly better than control and by month 24, (45% Apligraf sites had normal pigmentation compared with 13% of control sites (p=0.0005). Similarly, by month 24, 47% of patients had normal vascularity at the Apligraf site compared with 16% of patients at the control site.
Scar Assessment. Vancouver burn scar assessment scores were based on
clinical evaluations of graft pigmentation, vascularity, pliability, and
height. Normal assessment of graft appearance resulted in a score of zero
and the highest possible score when readings were a maximum on all four
markers was 13 points. The results comparing Apligraf vs. control were
analyzed by the paired t-test.
Mohs micrographic surgery is now
universally recognized as a precise method for treating skin cancers. It is
especially effective in cancers of the face and other sensitive areas because it
can eliminate virtually all the cancer cells while causing minimal damage to the
surrounding normal skin. Mohs micrographic surgery is also ideal for the removal
of recurrent skin cancers -- tumors that reappear after treatment and can plague
a patient repeatedly. As a study by Eaglstein, Alvarez et. al. indicates, this
surgery creates relatively deep skin wounds, which can be effectively treated
with Apligraf (Eaglstein,
Alvarez et. al. Dermatol Surg. 25:3:1999)
.One hundred and seven patients participated in this study. The tissue-engineered skin was applied once, immediately after excisional surgery and patients were followed for up to one year. One such patient who underwent Mohs Micrographic surgery and subsequent Apligraf treatment is presented below.
|Excision site immediately after surgery||Day 7 after Apligraf application|
after Apligraf application
Squamous cell carcinoma (SCC) is a
malignant neoplasm of keratinocytes with many features, one of which is the
production of keratin. Etiology, histology, and clinical presentations vary. SCC
can be categorized histologically into in situ (intraepidermal) or invasive
(penetrating the dermal-epidermal junction). Some examples of in situ SCC
include Bowen's disease and erythroplasia of Queyrat (legion of the genitalia).
SCC of the lip is one example of invasive carcinoma. Squamous cell carcinoma is
the second most common skin cancer after basal cell carcinoma. It typically
occurs on sun-exposed areas of the body and is more common in light-skinned men
greater than 55 years. The incidence of SCC increases closer to the equator.
Predisposing factors for SCC include a family history of skin cancer, precursor
lip lesions from smoking, actinic keratosis, old burn scars, immunosuppression,
ultraviolet radiation, radiation therapy, and chemical carcinogens such as soot
and arsenic. The lesions progressively increase in size either rapidly over
months or slowly over years. They typically are firm, skin-colored, occasionally
red or yellow, papules, nodules, or plaques, that are smooth, verrucous,
crusted, ulcerated, or hyperkeratotic, occurring in skin or on mucous membranes.
Lesions on the lower lip, or in a scar, have up to a 20% probability of
metastasizing. Lesions on sun-damaged skin have a 2% tendency to metastasize.
Metastasis is primarily by way of the lymphatics, generally first to regional
lymph nodes. Metastasis by hematogenous spread to distant sites can occur, most
commonly to the brain, lungs, liver, bone, or skin. In situ Squamous Cell
Carcinoma (Bowen's Disease): an intraepidermal or in situ squamous cell
carcinoma. It appears as a slowly enlarging erythematous, well defined plaque
usually slightly scaly and crusted. These lesions vary in size from a few
millimeters to several centimeters. They are generally solitary and occur on
either sun-exposed or sun-protected areas. As with other excisional wounds,
these lesions can be healing using treatment with Apligraf ( Eaglstein, Alvarez
et. al. Dermatol Surg. 25:3:1999).
One such patient who had a squamous cell carcinoma removed and received
Apligraf treatment is captured below
One such patient who had a squamous cell carcinoma removed and received Apligraf treatment is captured below
|Day 0: Immediately after excision||1 week|
Epidermolysis bullosa (EB) comprises
a group of genetically determined skin fragility disorders characterized by
blistering of the skin and mucosae following mild mechanical trauma (Pearson. Arch
Dermatol.1988;124:718-725). Most forms of inherited EB are characterized by
a lifetime of blister and wound formation. Although some forms of inherited EB
are associated with normal longevity, several forms of severe inherited EB are
associated with significant morbidity and increased mortality as either a direct
or indirect result of the EB. Death may occur from the first days of life to the
first 3 decades in severely affected patients. Death usually occurs because of
infections in patients who are nutritionally compromised and anemic. There
is no specific treatment for any form of EB, and the mainstay of clinical
management is based on protection and avoidance of provoking factors. At
present, wound treatment of inherited EB is only supportive. Unfortunately,
these wounds tend to heal slowly and on some occasions fail to heal, becoming
chronic wounds. There is a pressing need for an effective means to halt and
possibly reverse the relentless progression toward chronic wound formation in
some forms of the disease. A recent study conducted by Falabella and associates
has revealed the efficacy of Apligraf in treating EB (Falabella,
Valencia, et. al. Arch Dermatol. 26 (10): 2000).
In this study, tissue-engineered skin was applied to the wounds of patients
with EB. The tissue-engineered skin was not clinically rejected, has proven very
safe, and most often induced rapid healing, indicating a potential role in the
management of EB wounds.
In this study, tissue-engineered skin was applied to the wounds of patients with EB. The tissue-engineered skin was not clinically rejected, has proven very safe, and most often induced rapid healing, indicating a potential role in the management of EB wounds.
|Day 0: Two acute wounds on the foot of a patient with the Weber-Cockayne variant of epidermolysis bullosa simplex.||Day 5: after treatment with Apligraf, there is apparent uniform graft take throughout both lesions.||Week 6: the treated sites are outlined. They remained healed at the last clinic visit (week 18).|
"Necrobiosis lipoidica is a rare cutaneous complication of diabetes mellitus. The etiology is probably multifactorial with microangiopathy, immune complex formation, abnormal collagen synthesis and breakdown all thought to play a part." (Owen, Murphy, et. al. Clin Exper Derm. 26 (2): 2001. pp176-178). Unfortunately, necrobiosis lipoidica often proves very resistant to treatment. Nevertheless, Owen, Murphy et. al. report a case of a 44-year-old woman with ulcerated necrobiosis lipoidica that healed following grafting with a tissue-engineered living skin tissue.
|Presentation of ulcerated necrobiosis lipoidica||Eighteen weeks after initial treatment with a living skin equivalent|