Download Bio-Engineered Skin and Soft Tissue Substitutes

Bio-Engineered Skin and Soft Tissue Substitutes
Protocol
(701113)
Medical Benefit
Preauthorization
Yes
Effective Date: 10/01/16
Next Review Date: 07/17
Review Dates: 03/12, 03/13, 03/14, 03/15, 07/15, 07/16
Preauthorization is required.
The following Protocol contains medical necessity criteria that apply for this service. The criteria
are also applicable to services provided in the local Medicare Advantage operating area for those
members, unless separate Medicare Advantage criteria are indicated. If the criteria are not met,
reimbursement will be denied and the patient cannot be billed. Please note that payment for
covered services is subject to eligibility and the limitations noted in the patient’s contract at the
time the services are rendered.
Populations
Individuals:
• With conditions
requiring surgical repair
Individuals:
• With chronic wounds
Individuals:
• With burns, skin grafts,
or traumatic wounds
Interventions
Comparators
Outcomes
Interventions of interest are: Comparators of interest are: Relevant outcomes include:
• Bio-engineered soft
• Surgical repair alone
• Symptoms
• Morbid events
tissue substitutes
• Functional outcomes
• Quality of life
• Treatment-related morbidity
Interventions of interest are: Comparators of interest are: Relevant outcomes include:
• Bio-engineered skin
• Standard wound care
• Disease-specific survival
• Symptoms
substitutes
• Change in disease status
• Morbid events
• Quality of life
Interventions of interest are: Comparators of interest are: Relevant outcomes include:
• Bio-engineered skin
• Standard wound care
• Symptoms
• Morbid events
substitutes
• Functional outcomes
• Quality of life
• Treatment-related morbidity
Description
Bio-engineered skin and soft tissue substitutes may be derived from human tissue (autologous or allogeneic),
nonhuman tissue (xenographic), synthetic materials, or a composite of these materials. Bio-engineered skin and
soft tissue substitutes are being evaluated for a variety of conditions, including breast reconstruction and to aid
healing of lower-extremity ulcers and severe burns. Acellular dermal matrix (ADM) products are also being
evaluated for soft tissue repair.
Summary of Evidence
Surgical Repair
In individuals who have conditions requiring surgical repair who receive bioengineered soft-tissue substitutes,
the evidence incudes randomized controlled trials (RCTs). Relevant outcomes are symptoms, morbid events,
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functional outcomes, quality of life, and treatment-related morbidity. Overall, there are a limited number of
soft-tissue substitutes, and the evidence is limited for any specific product. Following is a description of the
evidence for specific indications.
Breast Reconstruction
Results from an RCT and systematic reviews in unselected populations of breast reconstruction patients found
no benefit of ADM allograft compared to standard procedures for breast reconstruction. Reconstructions with
ADM have been reported to have higher complication rates than reconstructions without ADM. However, in
cases where there is limited breast tissue for coverage, including but not limited to when the use of ADM allows
a single-stage reconstruction, the available noncomparative studies may be considered sufficient to permit
conclusions about health outcomes that may inform patient decision making about reconstruction options. The
evidence is sufficient to determine qualitatively that the technology results in a meaningful improvement in the
net health outcome.
Interpositional Graft after Parotidectomy
Two lower quality controlled trials were identified that demonstrated a reduction in the incidence of Frey
syndrome with use of an interpositional ADM allograft. Neither study described the method of group assignment or blinding of patients and assessors. The evidence is insufficient to determine the effects of the technology on health outcomes.
Tendon Repair
One small RCT was identified that found improved outcomes with Graftjacket ADM allograft for rotator cuff
repair. Although these results are promising, additional study with a larger number of subjects is needed. The
evidence is insufficient to determine the effects of the technology on health outcomes.
Fistula Repair
One RCT was identified that used an ADM allograft that has not been cleared for marketing in the United States.
The evidence is insufficient to determine the effects of the technology on health outcomes.
Surgical Repair of Hernias or Parastomal Reinforcement
Several comparative studies including RCTs show no difference in outcome between tissue-engineered skin substitutes and either standard synthetic mesh or no reinforcement. The evidence is sufficient to determine qualitatively that the technology is unlikely to improve the net health outcome.
Oral Surgery
One RCT and one nonrandomized cohort were identified on the use of an ADM allograft (AlloDerm) for root
coverage therapy and oral cavity reconstruction following surgical removal of tumors. The studies show that
although use of an ADM allograft (AlloDerm) may possibly result in less scar contracture, important health outcomes were not improved over the standard of care. The evidence is insufficient to determine the effects of the
technology on health outcomes.
Laryngoplasty
The effect of micronized ADM (e.g., Cymetra) in laryngoplasty has been reported in case series. Longer term
controlled study in a larger number of patients is needed to determine the durability of this procedure and to
evaluate the safety of repeat injections. The evidence is insufficient to determine the effects of the technology
on health outcomes.
Tympanoplasty
AlloDerm ADM has been compared with native tissue grafts in a non-RCT. There was no significant difference in
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the success rate of the graft (88% for AlloDerm, 89% for fascia grafts, 96.7% for cartilage plus fascia), and there
was no significant difference in hearing between the groups at follow-up. Longer-term controlled study in a
larger number of patients is needed to determine the durability of this procedure. The evidence is insufficient to
determine the effects of the technology on health outcomes.
Chronic Wounds
In individuals with chronic wounds who receive bioengineered skin substitutes, the evidence includes RCTs.
Relevant outcomes include disease-specific survival, symptoms, change in disease status, morbid events, and
quality of life. Overall, the number of bio-engineered skin substitutes is large, but the evidence is limited for any
specific product. Relatively few products have been compared with the standard of care, and only for some
indications. Comparative trials have been identified for use in lower-extremity ulcers (diabetic or venous) and
for treatment of burns. In these trials, the healing rates improved roughly 15% to 20%. Several other products/
indications are supported by a U.S. Food and Drug Administration (FDA) humanitarian device exemption.
Following is a description of the evidence for specific indications.
Diabetic Lower-Extremity Ulcers
•
RCTs have demonstrated the efficacy of Apligraf, Dermagraft (living cell therapy), and Integra Dermal
Regeneration Template (biosynthetic) over the standard of care. Several amniotic membrane products have
also been shown to improve healing. The evidence is sufficient to determine qualitatively that the
technology results in a meaningful improvement in the net health outcome.
•
Additional study with a larger number of subjects is needed to evaluate the effect of human ADM products
and xenogenic skin substitutes (e.g., Oasis Wound Matrix and PriMatrix) in comparison with the current
standard of care. The evidence is insufficient to determine the effects of the technology on health outcomes.
Lower-Extremity Ulcers due to Venous Insufficiency
•
RCTs have demonstrated the efficacy of Apligraf living cell therapy and xenogenic Oasis Wound Matrix over
the standard of care. The evidence is sufficient to determine qualitatively that the technology results in a
meaningful improvement in the net health outcome.
•
In a moderately large RCT, Dermagraft was not shown to be more effective than controls in the primary or
secondary end points for the entire population and was slightly more effective than controls (an 8%-15%
increase in healing) only in subgroups of patients with ulcer duration of 12 months or less or size of 10 cm or
less. The evidence is insufficient to determine the effects of the technology on health outcomes.
•
In a randomized comparison of EpiFix amniotic membrane versus standard of care that used a primary
outcome measure of 40% wound healing, there was no difference between one or two applications of EpiFix
and no difference between the experimental and controls groups in complete wound closure at four weeks.
Additional study is needed. Additional study with a larger number of subjects is also needed to evaluate the
effect of the xenogenic PriMatrix skin substitute in comparison with the current standard of care. The
evidence is insufficient to determine the effects of the technology on health outcomes.
Dystrophic Epidermolysis Bullosa
OrCel (living cell therapy) has received FDA under a humanitarian device exemption. Although case series studies
have shown good outcomes in this condition, as this is a rare disorder, it is unlikely that RCTs will be undertaken.
The evidence is insufficient to determine the effects of the technology on health outcomes.
Burns, Skin Grafts, and Traumatic Wounds
In individuals with burns, skin grafts, and traumatic wounds who receive bio-engineered soft-tissue substitutes, the evidence includes RCTs. Relevant outcomes are symptoms, morbid events, functional outcomes,
quality of life, and treatment-related morbidity. Overall, there are a limited number of soft-tissue substitutes,
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and the evidence is limited for any specific product. Following is a description of the evidence for specific
indications.
Ocular Burns
An RCT of amniotic membrane transplantation did not demonstrate improved outcomes compared to medical
therapy. The evidence is insufficient to determine the effects of the technology on health outcomes.
Nonocular Burns
Epicel (living cell therapy) is FDA-approved under a humanitarian device exemption for the treatment of deep
dermal or full-thickness burns comprising a total body surface area of 30% or more. A case series showed
permanent coverage of a mean of 26% of total BSA. The evidence is insufficient to determine the effects of the
technology on health outcomes.
Comparative studies have demonstrated improved outcomes for the biosynthetic skin substitute Integra Dermal
Regeneration Template for the treatment of burns. The evidence is sufficient to determine qualitatively that the
technology results in a meaningful improvement in the net health outcome.
Skin Grafts
Keramatrix (xenogenic skin substitute) was compared with standard of care in a small RCT for healing of skin graft
donor sites. Overall results are equivocal. Study in a larger number of patients/wounds is needed. The evidence is
insufficient to determine the effects of the technology on health outcomes.
Traumatic Wounds
Use of biosynthetic Integra Dermal Regeneration Template has been reported in small case series (less than 20
patients) for the treatment of severe wounds with exposed bone, joint, and/or tendon. Controlled trials are
needed to evaluate this product/indication. The evidence is insufficient to determine the effects of the
technology on health outcomes.
Clinical Input
Clinical input was obtained on several occasions. The input considered ADM products to be medically necessary
for breast reconstruction and for the various products to be similar in efficacy. Input in 2014 was mixed regarding the efficacy of amniotic membrane and xenogenic products.
It was concluded that, given the extensive data from case series, as well as the clinical input obtained about the
usefulness of this procedure in providing inferolateral support for breast reconstruction, this procedure was
changed to medically necessary in breast reconstruction when there is insufficient tissue expander or implant
coverage by the pectoralis major muscle and additional coverage is required; when there is viable but compromised or thin postmastectomy skin flaps that are at risk of dehiscence or necrosis; or when the inframammary
fold and lateral mammary folds have been undermined during mastectomy and reestablishment of these
landmarks is needed.
Policy
Breast reconstructive surgery using allogeneic acellular dermal matrix products* (including each of the
following: AlloDerm®, AlloMaxTM, AlloMend®, DermaMatrixTM, FlexHD®, GraftJacket®; see Policy Guidlelines)
may be considered medically necessary,
•
when there is insufficient tissue expander or implant coverage by the pectoralis major muscle and additional
coverage is required,
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•
when there is viable but compromised or thin post-mastectomy skin flaps that are at risk of dehiscence or
necrosis, or
•
the inframammary fold and lateral mammary folds have been undermined during mastectomy and reestablishment of these landmarks is needed.
Treatment of chronic, noninfected, full-thickness diabetic lower extremity ulcers using the following tissueengineered skin substitutes may be considered medically necessary:
•
Apligraf®**
•
Dermagraft®**
•
Integra® Dermal Regeneration Template
•
Amniotic Membrane Graft* (including each of the following: Biovance®, Epifix®, Grafix™)
Treatment of chronic, noninfected, partial- or full-thickness lower extremity skin ulcers due to venous insufficiency, which have not adequately responded following a one-month period of conventional ulcer therapy, using
the following tissue-engineered skin substitutes may be considered medically necessary:
•
Apligraf®**
•
Oasis™ Wound Matrix***
Treatment of dystrophic epidermolysis bullosa using the following tissue-engineered skin substitutes may be
considered medically necessary:
•
OrCel™ (for the treatment of mitten-hand deformity when standard wound therapy has failed and when
provided in accordance with the humanitarian device exemption [HDE] specifications of the FDA)****
Treatment of second- and third-degree burns using the following tissue-engineered skin substitutes may be
considered medically necessary:
•
Epicel® (for the treatment of deep dermal or full-thickness burns comprising a total body surface area of
30% or more when provided in accordance with the HDE specifications of the FDA)****
•
Integra Dermal Regeneration Template™**
*Banked Human Tissue
**FDA premarket approval
***FDA 510(k) cleared
****FDA-approved under a humanitarian device exemption (HDE)
All other uses of bio-engineered skin and soft tissue substitutes listed above are considered investigational.
All other skin and soft tissue substitutes not listed above are considered investigational, including, but not
limited to:
•
ACell® UBM Hydated Wound
Dressing
•
Allowrap™
•
Avaulta Plus™
•
Alphaplex™ with MariGen
Omega3™
•
AxoGuard® Nerve Protector
(AxoGen)
•
ACell® UBM Lyophilized Wound
Dressing
•
Amniofix®
•
BioDfence/BioDfactor
•
Affinity™
•
Aongen™ Collagen Matrix
•
CellerateRX®
•
AlloPatch HD™
•
ArthroFlex™ (FlexGraft)
•
Clarix® Flo
•
AlloSkin™
•
Atlas Wound Matrix
•
Collagen Sponge (Innocoll)
•
AlloSkin™ RT
•
Avagen Wound Dressing
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Collagen Wound Dressing (Oasis
Research)
•
GraftJacket® Xpress, injectable
•
Oasis® Ultra Tri-Layer Matrix
•
GUARDIAN
•
Permacol™
•
Collaguard®
•
HA Absorbent Wound Dressing
•
PriMatrix™
•
CollaSorb™
•
Helicoll
•
Primatrix™ Dermal Repair Scaffold
•
CollaWound™
•
Hyalomatrix® (Laserskin®)
•
Puros® Dermis
•
Collexa®
•
Hyalomatrix® PA
•
Repliform®
•
Collieva®
•
hMatrix®
•
Repriza™
•
Conexa™
•
Integra™ Flowable Wound Matrix
•
Revitalon
•
Coreleader Colla-Pad
•
Integra™ Bilayer Wound Matrix
•
SIS Wound Dressing II
•
CorMatrix®
•
Jaloskin®
•
SS Matrix™
•
CRXa™
•
MariGen
•
Stimulen™ Collagen
•
Cymetra®
•
MatriDerm®
•
StrataGraft
•
Dermadapt™ Wound Dressing
•
MatriStem® Burn Matrix
•
Strattice™ (xenograft)
•
Dermapure
•
MatriStem® Micromatrix
•
Suprathel®
•
Dermavest™
•
MatriStem® Wound Matrix
•
SurgiMend®
•
DressSkin
•
Matrix Collagen Wound Dressing
•
Talymed®
•
Durepair Regeneration Matrix®
•
Matrix HD™
•
TenoGlide™
•
Endoform Dermal Template™
•
MediHoney®
•
TheraForm™ Standard/Sheet
•
ENDURAgen™
•
Mediskin®
•
TheraSkin®
•
Excellagen
•
MemoDerm™
•
Unite® Biomatrix
•
E-Z Derm™
•
Neox® Flo
•
Veritas® Collagen Matrix
•
FortaDerm™ Wound Dressing
•
NuShield™
•
GammaGraft
•
Oasis® Burn Matrix
•
Policy Guidelines
Clinical input indicated that the various acellular dermal matrix (ADM) products used in breast reconstruction
have similar efficacy. The products listed are those that have been identified for use in breast reconstruction.
Additional ADM products may become available for this indication.
Medicare Advantage
Products are listed alphabetically. Please also note Medicare Advantage guidelines.
AlloDerm® Regenerative Tissue Matrix
AlloDerm® Regenerative Tissue Matrix is considered medically necessary for the following indications:
•
Abdominal wall reconstruction
•
Breast reconstruction after mastectomy for breast cancer
Poor general medical condition or any pathology that would limit the blood supply and compromise healing
should be considered when selecting patients for implanting AlloDerm® Regenerative Tissue Matrix as such
conditions may compromise successful implantation.
Apligraf®
The patient must be competent and/or have the support system required to participate in follow-up care
associated with treatment of the wound with Apligraf®.
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Apligraf® will be considered medically necessary for the following:
•
•
•
When used with standard therapeutic compression for venous stasis ulcers (VSUs):
o
Only for ulcers that have failed to respond to documented conservative measures of greater than four
(4) weeks in duration, that have at minimum included regular dressing changes, debridement of necrotic
tissue and standard therapeutic compression. A “failed response” is defined as an ulcer that has
increased in size or depth, or for which there has been no change in baseline size or depth and no sign of
improvement or indication that improvement is likely, such as granulation, epithelialization, or progress
towards closing. Documentation of response, or lack thereof, requires measurement of the ulcer at
baseline, following cessation of conservative or conventional management. Documentation should also
include measurement of the ulcer immediately prior to the placement of Apligraf®.
o
Only when adequate treatment of the underlying disease process(es) contributing to the ulcer, e.g.,
hypertension, is provided and documented in conjunction with the treatment; and
o
Only for ulcers that are free of infection, redness, drainage, underlying osteomyelitis, surround cellulitis,
sinus tracts or tunnels, eschar or any necrotic material that could interfere with the adherence of
Apligraf® and wound healing.
When used with standard diabetic foot ulcer (DFU) care for neuropathic DFUs:
o
Only if the patient has the current medical diagnosis of either Type I or Type II diabetes mellitus;
o
Only if the patient does not have a current HbA1C reading exceeding 12%;
o
Only for full thickness ulcers of greater than three weeks in duration, which extend through the dermis
but without tendon, muscle, capsule or bone exposure;
o
Only when adequate treatment of the underlying disease process(es) contributing to the ulcer, e.g.,
diabetes is provided and documented in conjunction with treatment; and
o
Only for ulcers located on the foot or toes that are free of infection, redness, drainage, underlying
osteomyelitis, surrounding cellulitis, tunnels and tracts, eschar or any necrotic material that could
interfere with the adherence of Apligraf®, and the process of wound healing.
For both VSUs and DFUs all of the following must also be satisfied and documented:
o
The patient must have adequate circulation/oxygenation to support tissue growth/wound healing as
evidenced by physical examination (presence of acceptable peripheral pulses and/or Doppler toe signals
and/or ankle-brachial index [ABI] of no less than 0.65 in the limb undergoing the procedure);
o
Dermal-epidermal tissue (DET) treatment must be used in conjunction with following standard
conservative measures:

Use of pressure-reducing footwear;

A non-weight bearing regiment;

Debridement of necrotic and callused tissue when necessary; and

Acceptable methods of wound care, such as saline moistened dressings.
The use of Apligraf® on ulcers with any of the following conditions is considered not medically necessary:
•
cellulitis;
•
osteomyelitis;
•
necrotic ulcer;
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•
draining wound;
•
bone exposed- wound bed; or
•
clinically significant wound healing impairment due to uncontrolled diabetes.
Last Review Date: 07/16
The following uses of Apligraf® are considered not medically necessary:
•
Use of more than five applications for the same ulcer. (A single application for any particular ulcer is usually
all that is required to affect wound healing in those wounds that are likely to be helped by this therapy.
Treatment is usually expected to last no more than twelve (12) weeks and to involve a maximum of five
applications);
•
Re-application more frequently than once per week for the same ulcer;
•
Re-application where initial application has resulted in no decrease in size or depth or increase in
granulation tissue, epithelialization, or progress towards closing;
•
Re-treatment within one year following the last successful application;
•
Re-treatment of an ulcer following the unsuccessful treatment where it consisted of two failed applications.
Dermagraft®
Dermagraft® use is considered medically necessary in the following conditions:
When used with standard diabetic foot ulcer care for neuropathic diabetic foot ulcers (DFUs):
•
Only if patient has a current medical diagnosis of Type I or Type II of diabetes mellitus;
•
Only if the patient does not have a current HbA1C reading exceeding 12%;
•
Only for full thickness ulcers that have been in existence for greater than six weeks;
•
Only for ulcers which have failed to respond to documented conservative treatment measures of greater
than six weeks;
•
Only for ulcers located on the foot or toes that are free of infection, redness, drainage, underlying
osteomyelitis, surrounding cellulitis, sinus tracts or tunnels, eschar or any necrotic material that could
interfere with the adherence of Dermagraft®, and process of wound healing;
•
Only for ulcers which extend through the dermis but without tendon, muscle, capsule or bone exposure;
•
The patient must have adequate arterial blood supply as evidenced by ankle-brachial index (ABI) of 0.65 or
greater in limb undergoing the procedure.
Dermagraft® treatment must be used in conjunction with following standard conservative measures:
•
Use of pressure-reducing footwear;
•
A non-weight bearing regimen;
•
Debridement of necrotic and callused tissue when necessary;
•
Acceptable methods of wound care, such as saline moistened dressings; and
•
The patient must be competent and/or have the support system required to participate in follow-up care
associated with treatment of the wound with Dermagraft®.
The use of Dermagraft® on ulcers with any of the following conditions is considered not medically necessary:
•
cellulitis;
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•
osteomyelitis;
•
necrotic ulcer;
•
draining wound;
•
bone exposed-wound bed; or
•
clinically significant wound healing impairment due to uncontrolled diabetes.
Last Review Date: 07/16
Dermagraft® should not be used on wounds that have signs of clinical infections.
The following use of Dermagraft® is not medically necessary:
•
Continued reapplication of Dermagraft® when the treatment is unsuccessful after two applications as
evidenced by increased wound size over two successive weeks.
•
Retreatment of the same ulcer using Dermagraft® within one year following the last successful or
unsuccessful treatment .
As long as reasonable healing progress is noted, reapplication may continue to a maximum of eight applications
in 12 weeks.
EpiFix®
EpiFix® is considered medically necessary in the wound management for patients with neuropathic diabetic foot
ulcers (DFUs) and non-infected partial and full-thickness skin ulcers due to venous insufficiency, i.e., venous
stasis ulcers (VSUs) when the following criteria are met:
A. When used with standard diabetic foot ulcer care for neuropathic DFUs:
•
Only if the patient has a current medical diagnosis of either Type I or Type II diabetes mellitus
•
Only If the patient does not have a current HbA1c reading above 12%
•
Only for partial or full thickness ulcers of greater than four weeks in duration, with documented failure
of prior treatment to heal the wound
•
Ulcer extends through the dermis, with or without tendon, muscle, capsule or bone exposure
•
Ulcer exhibits no signs of infection
Patient must have adequate circulation to the affected extremity, as evidenced by one of the following
during the past 60 days:
•
TcPO2 with results greater than or equal to 30 mm HG; or
•
ABI with results of greater than or equal to 0.7 and less than or equal to 1.2; or
•
Doppler arterial waveforms which are triphasic or biphasic at the ankle of the affected leg.
The following conservative measures must be in place:
•
Debridement of necrotic tissue;
•
Non-weight bearing regimen;
•
Use of pressure-reducing footwear.
B. When used with standard therapeutic compression for venous stasis ulcers (VSUs):
•
Only for ulcers that have failed to respond to documented conservative measures of greater than four
(4) weeks in duration, that have at minimum included regular dressing changes, debridement of necrotic
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tissue and standard therapeutic compression. A “failed response” is defined as an ulcer that has
increased in size or depth, or for which there has been no change in baseline size or depth and no sign of
improvement or indication that improvement is likely, such as granulation, epithelialization, or progress
towards closing.
•
Conservative methods of wound care include wound tissue hydration with saline, non-adherent
dressings, moisture-donating or absorptive dressing (depending on amount of exudate), and
compression wraps.
•
Documentation of response, or lack thereof, requires measurement of the ulcer at baseline, following
cessation of conservative or conventional management. Documentation should also include
measurement of the ulcer immediately prior to the placement of EpiFix®.
•
Only when adequate treatment of the underlying disease process(es) contributing to the ulcer, e.g.
hypertension, is provided and documented in conjunction with the treatment; and
•
Only for ulcers that are free of infection, redness, drainage, underlying osteomyelitis, surrounding
cellulitis, sinus tracts or tunnels, eschar or any necrotic material that could interfere with the adherence
of Epifix® and wound healing.
The use of EpiFix® on ulcers with any one of the following conditions is considered not medically necessary:
•
Osteomyelitis
•
Cellulitis
•
Necrotic tissue
•
Draining wound
•
Exposed bone
•
Active infection at wound site
•
Patients who are currently receiving radiation therapy or chemotherapy
•
Patients with an allergy to Gentamycin or Streptomycin
•
Patients whose index diabetic foot ulcer is greater than 25 cm2
•
Treatment of the ulcer greater than twelve (12) weeks.
The following treatments with EpiFix® are considered not medically necessary:
•
Reapplication of EpiFix® within one week for the same ulcer. (Treatment with EpiFix® occurs weekly, and is
expected to last up to twelve (12) weeks.)
•
Re-treatment within one year following the last successful application with EpiFix®.
•
Re-treatment of an ulcer following the unsuccessful treatment where it consisted of two (2) failed EpiFix®
applications.
Grafix®
Grafix® is considered medically necessary in the wound management for patients with diabetic foot ulcers
(DFUs) when the following criteria are met:
When used with standard diabetic foot ulcer care for DFUs:
•
Only if the patient has the current medical diagnosis of either Type I or Type II diabetes mellitus
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•
Only if the patient does not have a current HbA1c reading above 12%
•
Only for partial or full thickness ulcers of greater than four weeks in duration, with documented failure of
prior treatment to heal the wound
•
Ulcer extends through the dermis, with or without tendon, muscle, capsule or bone exposure
•
Ulcer must exhibit no signs of infection
Patient must have adequate circulation to the affected extremity, as evidenced by one of the following during
the past 60 days:
•
TcPO2 with results ≥ 30mmHG; or
•
ABI with results of > 0.70 and < 1.20; or
•
Doppler arterial waveforms which are triphasic or biphasic at the ankle of the affected leg.
The following conservative measures must be in place:
•
Debridement of necrotic tissue;
•
Non-weight bearing regimen;
•
Use of pressure-reducing footwear.
The use of Grafix® on ulcers with any one of the following conditions is considered not medically necessary:
•
Osteomyelitis
•
Cellulitis
•
Necrotic tissue
•
Draining wound
•
Exposed bone
•
Active infection at wound site
•
Patients who are currently receiving radiation therapy or chemotherapy
•
Patients with an allergy to Gentamycin, Vancomycin and Amphotericin
•
Patients whose index diabetic foot ulcer is greater than 15 cm2
•
Treatment of the ulcer greater than twelve (12) weeks
These treatments with Grafix® are considered not medically necessary:
•
Reapplication of Grafix® within one week for the same ulcer. (Treatment with Grafix® occurs weekly, and is
expected to last up to twelve (12) weeks).
•
Re-treatment within one year following the last successful application with Grafix®.
•
Re-treatment of an ulcer following the unsuccessful treatment where it consisted of two (2) failed Grafix®
applications.
GRAFTJACKET® Regenerative Tissue Matrix-Ulcer Repair
GRAFTJACKET® Regenerative Tissue Matrix-Ulcer Repair must be used in conjunction with the following
standard conservative measures:
•
pressure-reducing footwear;
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•
non-weight bearing regimen;
•
debridement of necrotic and callused tissue when necessary; and
•
acceptable standard methods of wound care, such as saline moistened dressings.
Last Review Date: 07/16
The patient must be competent and/or have the support system required to participate in follow-up care
associated with treatment of the wound with GRAFTJACKET® Regenerative Tissue Matrix-Ulcer Repair.
GRAFTJACKET® Regenerative Tissue Matrix-Ulcer Repair will be considered medically necessary for the following
indications:
•
augmentation of repairs of large rotator cuff tears or ruptured calcaneal tendons;
•
treatment of neuropathic diabetic foot ulcers (DFU) with all the following conditions:
o
patient has a current medical diagnosis of either Type I or Type II diabetes mellitus; and
o
patient does not have a current HbA1C reading exceeding 12%; and
o
full thickness ulcers of greater than three weeks duration that extend through the dermis but without
tendon, muscle, capsule or bone exposure; and
o
underlying disease process(es) contributing to the ulcer, e.g., diabetes, is adequately treated and
documented; and
o
ulcers are located on the foot or toes and are free of infection, redness, drainage, underlying
osteomyelitis, surrounding cellulitis, tunnels or tracts, eschar or any necrotic material that could
interfere with the adherence of GRAFTJACKET® Regenerative Tissue Matrix-Ulcer Repair and the process
of wound healing; and
o
patient must have adequate arterial blood supply as evidenced by ankle-brachial index (ABI) of 0.65 or
greater in the limb undergoing the procedure.
The use of GRAFTJACKET® Regenerative Tissue Matrix-Ulcer Repair on ulcers with any of the following
conditions is considered not medically necessary:
•
cellulitis
•
osteomyelitis
•
necrotic ulcer
•
draining wound
•
bone exposed wound bed
•
clinically significant wound healing impairment due to uncontrolled diabetes, poor nutrition and/or general
medical condition
•
autoimmune connective tissue disease.
The following uses of GRAFTJACKET® matrix are considered not medically necessary:
•
Use of more than two applications for the same ulcer. (A single application for any particular ulcer is usually
all that is required to achieve wound healing in those wounds that are likely to be helped by this therapy.
Treatment is usually expected to last no more than twelve (12) weeks and to involve a maximum of two
applications);
•
Re-application within three weeks for the same ulcer;
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•
Re-application where initial application has resulted in no decrease in size or depth or increase in
granulation tissue, epithelialization, or progress towards closing;
•
Re-treatment within one year following the last successful application;
•
Re-treatment of an ulcer following two failed applications.
GRAFTJACKET® XPRESS Flowable Soft Tissue Scaffold
GRAFTJACKET® XPRESS Flowable Soft Tissue Scaffold is considered investigational.
HYALOMATRIX®
HYALOMATRIX® is considered medically necessary in the wound management for patients with neuropathic
diabetic foot ulcers (DFUs) and non-infected partial and full-thickness skin ulcers due to venous insufficiency,
i.e., venous stasis ulcers (VSUs) when the following criteria are met:
When used with standard diabetic foot ulcer care for neuropathic DFUs:
•
Only if the patient has the current medical diagnosis of either Type I or Type II diabetes mellitus
•
Only if the patient does not have a current HbA1c reading above 12%
•
Only for partial or full thickness ulcers of greater than four weeks in duration, with documented failure of
prior treatment to heal the wound
•
Ulcer extends through the dermis, with or without tendon, muscle, capsule or bone exposure
•
Ulcer must exhibit no signs of infection
Patient must have adequate circulation to the affected extremity, as evidenced by one of the following during
the past 60 days:
•
TcPO2 with results ≥ 30mmHG; or
•
ABI with results of ≥ 0.7 and ≤ 1.2; or
•
Doppler arterial waveforms which are triphasic or biphasic at the ankle of the affected leg.
The following conservative measures must be in place:
•
Debridement of necrotic tissue;
•
Non-weight bearing regimen;
•
Use of pressure-reducing footwear.
When used with standard therapeutic compression for venous stasis ulcers (VSUs):
•
Only for ulcers that have failed to respond to documented conservative measures of greater than four (4)
weeks in duration, that have at minimum included regular dressing changes, debridement of necrotic tissue
and standard therapeutic compression. A “failed response” is defined as an ulcer that has increased in size
or depth, or for which there has been no change in baseline size or depth and no sign of improvement or
indication that improvement is likely, such as granulation, epithelialization, or progress towards closing.
•
Conservative methods of wound care include wound tissue hydration with saline, non-adherent dressings,
moisture donating or absorptive dressing (depending on amount of exudate), and compression wraps.
•
Documentation of response, or lack thereof, requires measurement of the ulcer at baseline, following
cessation of conservative or conventional management. Documentation should also include measurement
of the ulcer immediately prior to the placement of HYALOMATRIX®.
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•
Only when adequate treatment of the underlying disease process(es) contributing to the ulcer, e.g.
hypertension, is provided and documented in conjunction with the treatment; and
•
Only for ulcers that are free of infection, redness, drainage, underlying osteomyelitis, surrounding cellulitis,
sinus tracts or tunnels, eschar or any necrotic material that could interfere with the adherence of
HYALOMATRIX® and wound healing.
The use of HYALOMATRIX® on ulcers with any one of the following conditions is considered not medically
necessary:
•
Osteomyelitis
•
Cellulitis
•
Necrotic tissue
•
Excessively draining wound
•
Active infection at wound site
•
Treatment of the ulcer greater than twelve (12) weeks
Treatment with HYALOMATRIX® is considered not medically necessary under the following conditions:
•
Reapplication within one week for the same ulcer. (Treatment with HYALOMATRIX® usually leads to the
desired clinical response with two to three applications. Refractory ulcers may require up to six treatments,
separated by as much as three weeks between applications.)
•
Re-treatment within one year following the last successful application.
•
Re-treatment of an ulcer following an unsuccessful treatment course which consisted of two failed
applications.
Integra®Omnigraft Dermal Regeneration Matrix
Integra®Omnigraft Dermal Regeneration Matrix is considered medically necessary for the treatment of partial
and full thickness neuropathic diabetic foot ulcers (DFUs) that are greater than six weeks in duration, with no
capsule, tendon, or bone exposed and when used in conjunction with standard diabetic ulcer care.
Integra®Omnigraft Dermal Regeneration Matrix is contraindicated for patients with clinically diagnosed infected
wounds and in patients with a known sensitivity to bovine collagen or chondroitin materials.
This product should be applied on the day of debridement, delaying the application may substantially impair the
take of the material to the wound bed.
Integra®Dermal Regeneration Template
Integra®Dermal Regeneration Template will be considered medically necessary for the following:
•
The treatment is for post excisional 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
physiological condition of the patient; or
•
The treatment is indicated for the repair of scar contractures secondary to third degree burns when other
therapies have failed, or when donor sites for repair are not sufficient or desirable due to the physiological
condition of the patient. These scars must be documented to be disabling (e.g., by limiting elasticity and
immobilizing the skin); and
•
The substitute skin product must be applied on the same day as the initial excision of the recipient site; and
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Bio-Engineered Skin and Soft Tissue Substitutes
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Each piece of this product is for a single use in a single patient only. The device is intended for one-time use.
The use of this product in patients with chemical, radiation, or electrical burns should be limited and based on
thorough evaluation of the wound by the surgeon. The wound must be documented to be suitable to excisional
therapy and that there is likelihood that a viable wound bed will be created by excision.
The product is contraindicated for patients with clinically diagnosed infected wounds.
In the vast majority of patients, only one application of this skin substitute product would be required.
Integra® Bilayer Wound Dressing
Integra® Bilayer Wound Dressing is considered investigational.
OASIS® Wound Matrix and OASIS® Ultra Tri-Layer Matrix
OASIS® Wound Matrix and OASIS® Ultra Tri-Layer Matrix should be used only in cases where the patient is
competent and/or has a support system to participate in the follow-up care associated with its use.
OASIS® Wound Matrix and OASIS® Ultra Tri-Layer Matrix will be considered medically necessary for the
following indications:
•
Partial and full thickness wounds
•
Pressure ulcer
•
Venous stasis ulcers (VSUs) – when ALL the following conditions are met:
•
o
The venous stasis ulcer has been present for greater than one month duration;
o
The venous stasis ulcer has failed to respond to documented conservative measures of at least four
weeks duration. A “failed response” is defined as an ulcer that has increased in size or depth, for which
there has been no change in baseline size or depth and no sign of improvement or indication that
improvement is likely, such as granulation, epithelialization, or progress towards closing;
o
Documentation of response or lack thereof requires measurement of the ulcer at baseline and at
completion of at least four weeks of standard conservative management. Documentation should also
include measurement of the ulcer immediately prior to the placement of OASIS® Wound Matrix and
OASIS® Ultra Tri-Layer Matrix and before each additional weekly placement;
o
Conservative methods of wound care include wound tissue hydration with saline, non-adherent
dressings, moisture-donating or absorptive dressing (depending on amount of exudate), and
compression wraps.
Chronic vascular ulcers
o
•
Ankle Brachial Index (ABI) when applicable must be greater than 0.7 mm HG, in the affected limb being
treated.
Neuropathic diabetic foot ulcers (DFUs) - when ALL the following conditions are met:
o
The patient is currently under management for either Type I or Type II diabetes mellitus;
o
The non-healing diabetic foot ulcer has been present for greater than one month and has a viable
wound bed with granulation tissue present;
o
Standard conservative wound care measures have been tried. Conservative measures include removal
of mechanical stress, debridement of necrotic tissue if present, and saline moistened dressings;
o
The ulcer is located on the foot or toes and there is no exposed bone, tendon, or fascia.
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Bio-Engineered Skin and Soft Tissue Substitutes
Last Review Date: 07/16
Surgical wounds (donor sites/grafts, post-Mohs surgery, post-laser surgery, wound dehiscence).
OASIS® Wound Matrix and OASIS® Ultra Tri-Layer Matrix is contraindicated in patients with the following history
or conditions and would be considered not medically necessary:
•
for individuals with rheumatoid arthritis;
•
history of radiation therapy to the ulcer site;
•
for uncontrolled congestive heart failure;
•
for severe arterial disease;
•
for persons receiving corticosteroids or immunosuppressive therapies;
•
for individuals with a history of collagen vascular disease;
•
malnutrition (albumin);
•
known allergy to porcine-derived products;
•
ulcers that are clinically infected;
•
uncontrolled diabetes (HgbA1c greater than 12%);
•
previous organ transplant;
•
individuals undergoing hemodialysis;
•
wounds with signs of cellulitis, osteomyelitis, or necrotic or avascular ulcer beds;
•
for ulcers with exposed bone, tendon, or fascia;
•
insufficient blood supply to the ulcer (TcPO2 @ less than 30 mm Hg, toe or ankle brachial index less than 0.7
mm Hg);
•
active Charcot joint disease or Sickle Cell disease;
•
third degree burns.
The application of OASIS® Wound Matrix and OASIS® Ultra Tri-Layer Matrix to human wounds requires
reapplication every five to seven days. Once correctly applied, the wound should be assessed every five to seven
days and if appropriate, additional applications of Oasis® should be performed.
If wounds/ulcers managed with OASIS® Wound Matrix or OASIS® Ultra Tri-Layer Matrix do not evidence a
measurable response after twelve weeks of applications, future applications are considered not medically
necessary.
Porcine (pig) skin dressings
For Medicare Advantage porcine (pig) skin dressings may be medically necessary as an occlusive dressing for
burns, donor sites of a homograft, and decubiti and other ulcers. The following are examples of products that
are derived from porcine, and because FDA approval is integral to the uses they are deemed reasonable and
necessary for, it should be considered:
•
Oasis™ Wound Matrix (medically necessary indications below)
•
Permacol™
PrimatrixTM Dermal Repair Scaffold
PrimatrixTM Dermal Repair Scaffold will be considered medically necessary for the following:
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•
Partial thickness wounds
•
Full thickness wounds with or without exposed bone and/or exposed tendon – when ALL the following
conditions are met:
o
The wound has been determined and documented to be full thickness with or without exposed
underlying structures.
o
The wound has been adequately debrided of necrotic and/or non-viable tissue and results in a bleeding
wound bed.
o
PriMatrix is adequately applied and secured in a manner that maintains contact with the wound bed.
o
A moist wound environment is maintained but excessive fluid/exudates accumulation is managed by
means of appropriate dressing.
o
The patient must have adequate arterial blood supply to support tissue growth.
•
Pressure ulcers
•
Diabetic ulcers – when ALL the following conditions are met:
•
o
The type 1 or type 2 diabetic is under current medical management; and
o
The diabetic foot ulcer has been present for a minimum of 30 days duration.
o
The diabetic foot ulcer must have failed to respond to documented conservative measures including
aggressive sharp or surgical debridement of necrotic tissue, saline moistened dressings and a nonweight bearing regime. Medical record documentation will contain evidence that the conservative
measures have failed as evidenced by an ulcer that has increased in size and/or depth or that there has
been no change in baseline size or depth with no sign of improvement or no indication that
improvement is likely.
o
The patient must have adequate arterial blood supply to support tissue growth.
o
The ulcer must be free of infection and underlying osteomyelitis.
Venous ulcers – when ALL the following conditions are met:
o
The venous stasis ulcer has been present for greater than two months duration and has been refractory
to the conservative treatment measures described below for greater than one month.
o
The venous stasis ulcer must have failed to respond to documented conservative measures including
aggressive sharp or surgical debridement of necrotic tissue, saline moistened dressings and compression
dressing. Medical record documentation will contain evidence that the conservative measures have
failed as evidenced by an ulcer that has increased in size and/or depth or that there has been no change
in baseline size or depth with no sign of improvement or no indication that improvement is likely.
o
PriMatrix is applied in conjunction with adequate compression dressing.
o
The patient must have adequate arterial blood supply to support tissue growth.
•
Surgical wounds (donor sites/grafts, post-Mohs surgery, podiatric, wound dehiscence)
•
Trauma wounds
•
Tunneled/undermined wounds
•
Draining wounds.
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PrimatrixTM Dermal Repair Scaffold is contraindicated and therefore will be considered not medically necessary
for the following:
•
Use in third-degree burns.
Reapplication is required. Once correctly applied, the wound should be assessed every five to seven days and if
appropriate, additional applications of PriMatrix™ Dermal Repair Scaffold should be performed. Treatment
courses in studies provided by the manufacturer typically varied between seven and thirteen weeks duration
and involved a maximum of five applications no less than two weeks apart.
TheraSKIN®
TheraSKIN® will be considered medically necessary for the same VSU and DFU criteria as Apligraf® above,
except conservative measures would have been required for six (6) weeks VSUs.
The use of Theraskin on ulcers with any of the following conditions is considered not medically necessary:
•
cellulitis;
•
osteomyelitis;
•
necrotic ulcer;
•
draining wound; or
•
clinically significant wound healing impairment due to uncontrolled diabetes.
The following treatments with Theraskin are considered not medically necessary:
•
The use of more than five applications for the same ulcer. (Treatment with TheraSkin® is usually expected to
last no more than twelve (12) weeks and to involve a maximum of five TheraSkin® applications for any ulcer
that initially qualifies for treatment.)
•
Re-application of TheraSkin® within one week for the same ulcer.
•
Re-application of TheraSkin® where initial application has resulted in no decrease in size or depth or
increase in granulation tissue, epithelialization, or progress towards closing.
•
Re-treatment within one year following the last successful application with TheraSkin®.
•
Re-treatment of an ulcer following the unsuccessful treatment where it consisted of two failed TheraSkin®
applications.
Medicare Advantage Policy Guidelines
In addition to the specific products discussed above, this is general information regarding biologic products for
wound treatment and surgical interventions.
Types of wound coverings, skin substitutes, or other tissue substitutes:
1. Dermal and/or epidermal, (substitute) tissue of human origin or non-human origin, with or without
bioengineered or processed elements, with or without metabolically active elements, solid or injectable;
2. Allograft skin for temporary wound closure;
3. Xenograft, skin (dermal), for temporary wound closure;
4. Tissue cultured epidermal autograft;
5. Tissue cultured allogeneic skin substitute;
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6. Tissue cultured allogeneic dermal substitute; and
7. Biologic Wound Dressings.
The Food and Drug Administration (FDA) distinguishes between products according to function (wound
management, e.g., wound dressings and wound treatment, e.g., bioactive skin substitutes.) The former (Class II)
requires 510(k) pre-market notification for FDA clearance while the latter (Class III) requires pre-market
approval.
Human tissue products (acellular) require no FDA clearance or approval and are intended for homologous use
only. [Title 21 Code of Federal Regulations (CFR), Section 1271.10(a) 2005]
Medicare Advantage considers Class II or Human Tissue products investigational unless otherwise specified in
the biologic product criteria above.
Medicare Advantage will consider the use of Class III products medically necessary when used in keeping with
the FDA’s approved indications for those products unless otherwise specified in the criteria above.
Also refer to the general business policy statements above when otherwise not specifically addressed in this
Medicare Advantage section and not contradictory to these general statements. For example, general business
policy statements and regulatory status sections above provide some FDA information for the following which
are not discussed separately in this Medicare Advantage criteria section: Epicel®, OrCel™, TransCyte™, and for
Dermagraft® for wounds related to dystrophic epidermolysis bullosa.
Background
Bio-engineered skin and soft tissue substitutes may be either acellular or cellular. Acellular products (e.g.,
dermis with cellular material removed) contain a matrix or scaffold composed of materials such as collagen,
hyaluronic acid, and fibronectin. Acellular dermal matrix products can differ in a number of ways, including as
species source (human, bovine, porcine), tissue source (e.g., dermis, pericardium, intestinal mucosa), additives
(e.g., antibiotics, surfactants), hydration (wet, freeze dried) and required preparation (multiple rinses,
rehydration).
Cellular products contain living cells such as fibroblasts and keratinocytes within a matrix. The cells contained
within the matrix may be autologous, allogeneic, or derived from other species (e.g., bovine, porcine). Skin
substitutes may also be composed of dermal cells, epidermal cells, or a combination of dermal and epidermal
cells and may provide growth factors to stimulate healing. Tissue-engineered skin substitutes can be used as
either temporary or permanent wound coverings.
There are a large number of potential applications for artificial skin and soft tissue products. One large category
is nonhealing wounds, which potentially encompasses diabetic neuropathic ulcers, vascular insufficiency ulcers,
and pressure ulcers. A substantial minority of such wounds do not heal adequately with standard wound care,
leading to prolonged morbidity and increased risk of mortality. For example, nonhealing lower-extremity
wounds represent an ongoing risk for infection, sepsis, limb amputation, and death. Bio-engineered skin and
soft tissue substitutes have the potential to improve rates of healing and reduce secondary complications.
The preferred outcomes for the healing of lower-extremity ulcers and burn wounds are the percentage of
patients with complete wound healing and the time to complete wound healing.1 The percentage of patients
with 50% wound healing and time to 50% wound healing have also been considered to be appropriate outcomes
for these conditions.2 The percent change in wound area at four weeks is predictive of complete healing at 12
weeks in patients with diabetic foot ulcers.3 Thus, minimal improvement at 30 days can be considered as an
indicator that a wound is unlikely to heal in patients with comorbidities that are known to affect wound healing.
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Other situations in which bio-engineered skin products might substitute for living skin grafts include certain
postsurgical states (e.g., breast reconstruction) in which skin coverage is inadequate for the procedure
performed, or for surgical wounds in patients with compromised ability to heal. Second- and third-degree burns
are another situation in which artificial skin products may substitute for auto- or allografts. Certain primary
dermatologic conditions that involve large areas of skin breakdown, (e.g., bullous diseases) may also be
conditions in which artificial skin products can be considered as substitutes for skin grafts. Acellular dermal
matrix products are also being evaluated in the repair of other soft tissues including rotator cuff repair, following
oral and facial surgery, hernias, and other conditions.
Regulatory Status
A large number of artificial skin products are commercially available or in development. The following summary
of commercially available skin substitutes describes those products that have substantial relevant evidence on
efficacy. Information on other artificial skin and soft tissue substitutes that are available in the United States
may be found in a 2012 Technology Assessment from the Agency for Healthcare Research and Quality.4
Acellular Dermal Matrix Products
Allograft ADM products derived from donated human skin tissue are supplied by tissue banks compliant with
standards of the American Association of Tissue Banks (AATB) and U.S. Food and Drug Administration (FDA)
guidelines. The processing removes the cellular components (i.e., epidermis and all viable dermal cells) that can
lead to rejection and infection. ADM products from human skin tissue are regarded as minimally processed and
not significantly changed in structure from the natural material; FDA classifies it as banked human tissue and
therefore, does not require FDA approval.
•
AlloDerm® (LifeCell Corp.) is an ADM (allograft) tissue-replacement product that is created from native
human skin and processed so that the basement membrane and cellular matrix remain intact. Originally,
AlloDerm required refrigeration and rehydration before use. It is currently available in a ready-to-use
product that is stored at room temperature. An injectable micronized form of AlloDerm (Cymetra) is
available.
•
AlloMax™ Surgical Graft (Bard Davol) is an acellular non-cross-linked human dermis allograft. (AlloMax was
previously marketed as NeoForm™.)
•
FlexHD® (Ethicon) is an acellular hydrated dermis derived from donated human allograft skin. The
Musculoskeletal Transplant Foundation acquires and processes the tissue.
•
DermACELL™ (LifeNet Health) is an allogeneic ADM processed with proprietary technologies MATRACELL®
and PRESERVON®.
•
DermaMatrix™ (Synthes) is a freeze-dried ADM derived from donated human skin tissue. DermaMatrix
Acellular Dermis is processed by the Musculoskeletal Transplant Foundation® (MTF®).
•
DermaPure™ (Tissue Regenix Wound Care) is a single-layer decellularized human dermal allograft for the
treatment of acute and chronic wounds.
•
Graftjacket® Regenerative Tissue Matrix (also called Graftjacket Skin Substitute, KCI) is an acellular
regenerative tissue matrix that has been processed from human skin supplied from U.S. tissue banks. The
allograft is minimally processed to remove the epidermal and dermal cells, while preserving dermal
structure. Graftjacket Xpress® is an injectable product.
FDA product code: FTM, OXF.
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Xenogenic Products
Keramatrix® (Keraplast Research) is an open-cell foam comprised of freeze-dried keratin that is derived from
acellular animal protein. In 2009, it was cleared for marketing by FDA through the 510(k) marketing process
under the name of Keratec. The wound dressings are indicated in the management of the following types of dry,
light, and moderately exudating partial and full-thickness wounds, pressure (stage I-IV) and venous stasis ulcers,
ulcers caused by mixed vascular etiologies, diabetic ulcers, donor sites, and grafts.
Helicoll (Encol) is an acellular collagen matrix from bovine dermis. In 2004, it was cleared by FDA through the
510(k) process for topical wound management that includes partial and full-thickness wounds, pressure ulcers,
venous ulcers, chronic vascular ulcers, diabetic ulcers, trauma wounds (e.g., abrasions, lacerations, seconddegree burns, skin tears), and surgical wounds including donor sites/grafts.
Permacol™ (Covidien) is xenogeneic and composed of cross-linked porcine dermal collagen. Cross-linking
improves the tensile strength and long-term durability, but decreases pliability.
PriMatrix™ (TEI Biosciences) is a xenogeneic ADM processed from fetal bovine dermis. It was cleared for
marketing by FDA through the 510(k) process for partial- and full-thickness wounds; diabetic, pressure, and
venous stasis ulcers; surgical wounds; and tunneling, draining, and traumatic wounds. FDA product code: KGN.
SurgiMend® PRS (TEI Biosciences) is a xenogeneic ADM processed from fetal bovine dermis. This product is
currently undergoing an FDA-regulated investigational device exemption (IDE) trial for breast reconstruction.
Strattice™ Reconstructive Tissue Matrix (LifeCell Corp.) is a xenogenic non-cross-linked porcine-derived ADM.
There are pliable and firm versions, which are stored at room temperature and come fully hydrated.
OASIS™ Wound Matrix (Cook Biotech) is a xenogeneic collagen scaffold derived from porcine small intestinal
mucosa. In 2000, it was cleared for marketing by FDA through the 510(k) process for the management of partialand full-thickness wounds including pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers,
tunneled undermined wounds, surgical wounds, trauma wounds, and draining wounds. FDA Product code: KGN.
Amniotic Membrane Products
Amniotic membrane consists of two conjoined layers, the amnion and chorion, and forms the innermost lining
of the amniotic sac or placenta.5 It is harvested immediately after birth, cleaned, sterilized, and either fresh
frozen or dehydrated. Human amniotic membrane is considered to be minimally processed and not significantly
changed in structure from the natural material; FDA classifies it as banked human tissue and, therefore, it does
not require FDA approval. Amniotic membrane sheet products include Affinity™ (NuTech Medical), AlloWrap™
(AlloSource), AmnioBand and GUARDIAN (Musculoskeletal Transplant Foundation), AmnioGraft® (Bio-Tissue),
BioDfence™ and BioDDryFlex® (both from BioD), Biovance® (Alliqua Biomedical), Dermavest™ and Plurivest™
(Aedicell), EpiFix® (dehydrated-MiMedix) Neox®1000 (Amniox® Medical), Grafix® Prime and Grafix® Core
(cryopreserved, Osiris), NuShield™ (NuTech Medical), Revitalon™ (previously known as AmnioClear, Medline
Industries). Injectable amniotic membrane products, such as AmnioFix® (MiMedix), are not discussed in this
Protocol.
Living Cell Therapy
Apligraf® (Organogenesis) is a bilayered living cell therapy composed of an epidermal layer of living human
keratinocytes and a dermal layer of living human fibroblasts. Apligraf® is supplied as needed, in one size, with a
shelf-life of 10 days. In 1998, it was approved by FDA for use in conjunction with compression therapy for the
treatment of noninfected, partial- and full-thickness skin ulcers due to venous insufficiency and in 2001 for fullthickness neuropathic diabetic lower-extremity ulcers nonresponsive to standard wound therapy. FDA product
code: FTM.
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Dermagraft® (Organogenesis) is composed of cryopreserved human-derived fibroblasts and collagen derived
from newborn human foreskin and cultured on a bioabsorbable polyglactin mesh scaffold. Dermagraft has been
approved by FDA for repair of diabetic foot ulcers. FDA product code: PFC.
TheraSkin® (Soluble Systems) is a cryopreserved human skin allograft composed of living fibroblasts and
keratinocytes and an extracellular matrix in epidermal and dermal layers. TheraSkin® is derived from human skin
allograft in compliance with the AATB and FDA guidelines. It is considered a minimally processed human cell,
tissue, and cellular- and tissue-based product by the FDA.
Epicel® (Genzyme Biosurgery) is a cultured epithelial autograft and is FDA-approved under an HDE for the
treatment of deep dermal or full-thickness burns comprising a total body surface area of 30% or more. It may be
used in conjunction with split-thickness autografts or alone in patients for whom split-thickness autografts may
not be an option due to the severity and extent of their burns. FDA product code: OCE.
OrCel™ (Forticell Bioscience; formerly Composite Cultured Skin) is an absorbable allogeneic bilayered cellular
matrix, made of bovine collagen, in which human dermal cells have been cultured. It was approved by FDA
premarket approval for healing donor site wounds in burn victims and under an HDE for use in patients with
recessive dystrophic epidermolysis bullosa undergoing hand reconstruction surgery to close and heal wounds
created by the surgery, including those at donor sites. FDA product code: ODS.
Biosynthetic Products
Biobrane®/Biobrane-L (Smith and Nephew) is a biosynthetic wound dressing constructed of a silicon film with a
nylon fabric partially imbedded into the film. The fabric creates a complex three-dimensional structure of trifilament thread, which chemically binds collagen. Blood/sera clot in the nylon matrix, adhering the dressing to the
wound until epithelialization occurs. FDA product code: FRO.
Integra® Dermal Regeneration Template (marketed as Omnigraft Dermal Regeneration Matrix, Integra
LifeSciences) is a bovine, collagen/glycosaminoglycan dermal replacement covered by a silicone temporary
epidermal substitute. It was approved by FDA for use in postexcisional treatment of life- threatening fullthickness or deep partial-thickness thermal injury where sufficient autograft is not available at the time of
excision or not desirable because of the physiologic condition of the patient. Integra™ Matrix Wound Dressing
and Integra™ meshed Bilayer Wound Matrix are substantially equivalent skin substitutes approved by FDA
through the 510(k) process for other indications. Integra® Bilayer Wound Matrix (Integra LifeSciences) is
designed to be used in conjunction with negative pressure wound therapy. The meshed bilayer provides a
flexible wound covering and allows drainage of wound exudate. FDA product code: MDD.
TransCyte™ (Advanced Tissue Sciences) consists of human dermal fibroblasts grown on nylon mesh, combined
with a synthetic epidermal layer and was approved by FDA in 1997. TransCyte is intended to be used as a
temporary covering over burns until autografting is possible. It can also be used as a temporary covering for
some burn wounds that heal without autografting.
Synthetic Products
Suprathel® (PolyMedics Innovations) is a synthetic copolymer membrane fabricated from a tripolymer of
polylactide, trimethylene carbonate, and s-caprolactone. It is used to provide temporary coverage of superficial
dermal burns and wounds. Suprathel® is covered with gauze and a dressing that is left in place until the wound
has healed.
Related Protocol
Autologous Platelet-Derived Growth Factors for Wound Healing and Other Non-Orthopedic Conditions
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Services that are the subject of a clinical trial do not meet our Technology Assessment Protocol criteria and are
considered investigational. For explanation of experimental and investigational, please refer to the Technology
Assessment Protocol.
It is expected that only appropriate and medically necessary services will be rendered. We reserve the right to
conduct prepayment and postpayment reviews to assess the medical appropriateness of the above-referenced
procedures. Some of this Protocol may not pertain to the patients you provide care to, as it may relate to
products that are not available in your geographic area.
References
We are not responsible for the continuing viability of web site addresses that may be listed in any references
below.
1.
U.S. Food and Drug Administration. Guidance for industry: Chronic cutaneous ulcer and burn wounds.
2006;
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2.
European Wound Management Association. Outcomes in controlled and comparative studies on nonhealing wounds: recommendations to improve the quality of evidence in wound management. J Wound
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Sheehan P, Jones P, Caselli A, et al. Percent change in wound area of diabetic foot ulcers over a 4-week
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Snyder DL, Sullivan N, Schoelles KM. Skin Substitutes for Treating Chronic Wounds. Research conducted by
the ECRI Institute Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare
Research and Quality (AHRQ), Rockville, MD (Contract Number: HHSA 290-2007-10063). 2012;
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Zelen CM, Snyder RJ, Serena TE, et al. The use of human amnion/chorion membrane in the clinical setting
for lower extremity repair: a review. Clin Podiatr Med Surg. Jan 2015; 32(1):135-146. PMID 25440424
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Davila AA, Seth AK, Wang E, et al. Human acellular dermis versus submuscular tissue expander breast
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Ho G, Nguyen TJ, Shahabi A, et al. A systematic review and meta-analysis of complications associated with
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22421476
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Kim JY, Davila AA, Persing S, et al. A meta-analysis of human acellular dermis and submuscular tissue
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Govshievich A, Somogyi RB, Brown MH. Conservative mastectomies and immediate reconstruction with the
use of ADMs. Gland Surg. Dec 2015; 4(6):453-462. PMID 26644999
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Matrix-Assisted Direct-to-Implant Breast Reconstruction. Ann Plast Surg. Feb 5 2016. PMID 26849284
Page 23 of 29
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Last Review Date: 07/16
11. Salzberg CA, Ashikari AY, Koch RM, et al. An 8-year experience of direct-to-implant immediate breast
reconstruction using human acellular dermal matrix (AlloDerm). Plast Reconstr Surg. Feb 2011; 127(2):514524. PMID 21285756
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130(5 Suppl 2):57S-66S. PMID 23096987
13. Preminger BA, McCarthy CM, Hu QY, et al. The influence of AlloDerm on expander dynamics and
complications in the setting of immediate tissue expander/implant reconstruction: a matched-cohort study.
Ann Plast Surg. May 2008; 60(5):510-513. PMID 18434824
14. Liu DZ, Mathes DW, Neligan PC, et al. Comparison of outcomes using AlloDerm versus FlexHD for implantbased breast reconstruction. Ann Plast Surg. May 2014; 72(5):503-507. PMID 23636114
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69(4):347-349. PMID 22868313
17. Butterfield JL. 440 Consecutive immediate, implant-based, single-surgeon breast reconstructions in 281
patients: a comparison of early outcomes and costs between SurgiMend fetal bovine and AlloDerm human
cadaveric acellular dermal matrices. Plast Reconstr Surg. May 2013; 131(5):940-951. PMID 23629076
18. Sinha UK, Saadat D, Doherty CM, et al. Use of AlloDerm implant to prevent frey syndrome after parotidectomy. Arch Facial Plast Surg. Jan-Feb 2003; 5(1):109-112. PMID 12533152
19. Ye WM, Zhu HG, Zheng JW, et al. Use of allogenic acellular dermal matrix in prevention of Frey’s syndrome
after parotidectomy. Br J Oral Maxillofac Surg. Dec 2008; 46(8):649-652. PMID 18547692
20. Athavale SM, Phillips S, Mangus B, et al. Complications of alloderm and dermamatrix for parotidectomy
reconstruction. Head Neck. Jan 2012; 34(1):88-93. PMID 21469246
21. Barber FA, Burns JP, Deutsch A, et al. A prospective, randomized evaluation of acellular human dermal
matrix augmentation for arthroscopic rotator cuff repair. Arthroscopy. Jan 2012; 28(1):8-15. PMID
21978432
22. ba-bai-ke-re AMM, Wen H, Huang HG, et al. Randomized controlled trial of minimally invasive surgery using
acellular dermal matrix for complex anorectal fistula. World J Gastroenterol. Jul 14 2010; 16(26):3279-3286.
PMID 20614483
23. Bellows CF, Smith A, Malsbury J, et al. Repair of incisional hernias with biological prosthesis: a systematic
review of current evidence. Am J Surg. Jan 2013; 205(1):85-101. PMID 22867726
24. Zhong T, Janis JE, Ahmad J, et al. Outcomes after abdominal wall reconstruction using acellular dermal
matrix: a systematic review. J Plast Reconstr Aesthet Surg. Dec 2011; 64(12):1562-1571. PMID 21624851
25. Espinosa-de-los-Monteros A, de la Torre JI, Marrero I, et al. Utilization of human cadaveric acellular dermis
for abdominal hernia reconstruction. Ann Plast Surg. Mar 2007; 58(3):264-267. PMID 17471129
26. Gupta A, Zahriya K, Mullens PL, et al. Ventral herniorrhaphy: experience with two different biosynthetic
mesh materials, Surgisis and Alloderm. Hernia. Oct 2006; 10(5):419-425. PMID 16924395
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27. Bochicchio GV, De Castro GP, Bochicchio KM, et al. Comparison study of acellular dermal matrices in
complicated hernia surgery. J Am Coll Surg. Oct 2013; 217(4):606-613. PMID 23973102
28. Bellows CF, Shadduck P, Helton WS, et al. Early report of a randomized comparative clinical trial of Strattice
reconstructive tissue matrix to lightweight synthetic mesh in the repair of inguinal hernias. Hernia. Apr
2014; 18(2):221-230. PMID 23543334
29. Fleshman JW, Beck DE, Hyman N, et al. A prospective, multicenter, randomized, controlled study of noncross-linked porcine acellular dermal matrix fascial sublay for parastomal reinforcement in patients
undergoing surgery for permanent abdominal wall ostomies. Dis Colon Rectum. May 2014; 57(5):623-631.
PMID 24819103
30. Novaes AB, Jr., de Barros RR. Acellular dermal matrix allograft. The results of controlled randomized clinical
studies. J Int Acad Periodontol. Oct 2008; 10(4):123-129. PMID 19055225
31. Girod DA, Sykes K, Jorgensen J, et al. Acellular dermis compared to skin grafts in oral cavity reconstruction.
Laryngoscope. Nov 2009; 119(11):2141-2149. PMID 19650133
32. Milstein CF, Akst LM, Hicks MD, et al. Long-term effects of micronized Alloderm injection for unilateral
vocal fold paralysis. Laryngoscope. Sep 2005; 115(9):1691-1696. PMID 16148719
33. Vos JD, Latev MD, Labadie RF, et al. Use of AlloDerm in type I tympanoplasty: a comparison with native
tissue grafts. Laryngoscope. Sep 2005; 115(9):1599-1602. PMID 16148702
34. Santema TB, Poyck PP, Ubbink DT. Skin grafting and tissue replacement for treating foot ulcers in people
with diabetes. Cochrane Database Syst Rev. 2016; 2:CD011255. PMID 26866804
35. Veves A, Falanga V, Armstrong DG, et al. Graftskin, a human skin equivalent, is effective in the management
of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial.
Diabetes Care. Feb 2001; 24(2):290-295. PMID 11213881
36. Blue Cross and Blue Shield Association Technology Evaluation Center. Graftskin for the treatment of skin
ulcers. TEC Assessments. 2001; Volume 16, Tab 12.
37. Steinberg JS, Edmonds M, Hurley DP, Jr., et al. Confirmatory data from EU study supports Apligraf for the
treatment of neuropathic diabetic foot ulcers. J Am Podiatr Med Assoc. Jan-Feb 2010; 100(1):73-77. PMID
20093548
38. Kirsner RS, Warriner R, Michela M, et al. Advanced biological therapies for diabetic foot ulcers. Arch
Dermatol. Aug 2010; 146(8):857-862. PMID 20713816
39. Marston WA, Hanft J, Norwood P, et al. The efficacy and safety of Dermagraft in improving the healing of
chronic diabetic foot ulcers: results of a prospective randomized trial. Diabetes Care. Jun 2003; 26(6):17011705. PMID 12766097
40. Frykberg RG, Marston WA, Cardinal M. The incidence of lower-extremity amputation and bone resection in
diabetic foot ulcer patients treated with a human fibroblast-derived dermal substitute. Adv Skin Wound
Care. Jan 2015; 28(1):17-20. PMID 25407083
41. Sanders L, Landsman AS, Landsman A, et al. A prospective, multicenter, randomized, controlled clinical trial
comparing a bioengineered skin substitute to a human skin allograft. Ostomy Wound Manage. Sep 2014;
60(9):26-38. PMID 25211605
42. Brigido SA, Boc SF, Lopez RC. Effective management of major lower extremity wounds using an acellular
regenerative tissue matrix: a pilot study. Orthopedics. Jan 2004; 27(1 Suppl):s145-149. PMID 14763548
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43. Reyzelman A, Crews RT, Moore JC, et al. Clinical effectiveness of an acellular dermal regenerative tissue
matrix compared to standard wound management in healing diabetic foot ulcers: a prospective,
randomised, multicentre study. Int Wound J. Jun 2009; 6(3):196-208. PMID 19368581
44. Reyzelman AM, Bazarov I. Human acellular dermal wound matrix for treatment of DFU: literature review
and analysis. J Wound Care. Mar 2015; 24(3):128; 129-134. PMID 25764957
45. Brigido SA. The use of an acellular dermal regenerative tissue matrix in the treatment of lower extremity
wounds: a prospective 16-week pilot study. Int Wound J. Sep 2006; 3(3):181-187. PMID 16984575
46. Walters J, Cazzell S, Pham H, et al. Healing rates in a multicenter assessment of a sterile, room temperature, acellular dermal matrix versus conventional care wound management and an active comparator in
the treatment of full-thickness diabetic foot ulcers. Eplasty. 2016; 16:e10. PMID 26933467
47. Driver VR, Lavery LA, Reyzelman AM, et al. A clinical trial of Integra Template for diabetic foot ulcer treatment. Wound Repair Regen. Nov 12 2015; 23(6):891-900. PMID 26297933
48. Zelen CM, Serena TE, Denoziere G, et al. A prospective randomised comparative parallel study of amniotic
membrane wound graft in the management of diabetic foot ulcers. Int Wound J. Oct 2013; 10(5):502-507.
PMID 23742102
49. Zelen CM, Serena TE, Fetterolf DE. Dehydrated human amnion/chorion membrane allografts in patients
with chronic diabetic foot ulcers: a long term follow-up study. Wound Med. 2014; 4:1-4.
50. Smiell JM, Treadwell T, Hahn HD, et al. Real-world experience with a decellularized dehydrated human
amniotic membrane allograft. Wounds. Jun 2015; 27(6):158-169. PMID 26061491
51. Zelen CM, Gould L, Serena TE, et al. A prospective, randomised, controlled, multi-centre comparative
effectiveness study of healing using dehydrated human amnion/chorion membrane allograft, bioengineered skin substitute or standard of care for treatment of chronic lower extremity diabetic ulcers. Int
Wound J. Dec 2015; 12(6):724-732. PMID 25424146
52. Kirsner RS, Sabolinski ML, Parsons NB, et al. Comparative effectiveness of a bioengineered living cellular
construct vs. a dehydrated human amniotic membrane allograft for the treatment of diabetic foot ulcers in
a real world setting. Wound Repair Regen. Sep 2015; 23(5):737-744. PMID 26100572
53. Lavery LA, Fulmer J, Shebetka KA, et al. The efficacy and safety of Grafix((R)) for the treatment of chronic
diabetic foot ulcers: results of a multi-centre, controlled, randomised, blinded, clinical trial. Int Wound J.
Oct 2014; 11(5):554-560. PMID 25048468
54. Niezgoda JA, Van Gils CC, Frykberg RG, et al. Randomized clinical trial comparing OASIS Wound Matrix to
Regranex Gel for diabetic ulcers. Adv Skin Wound Care. Jun 2005; 18(5 Pt 1):258-266. PMID 15942317
55. Kavros SJ, Dutra T, Gonzalez-Cruz R, et al. The use of PriMatrix, a fetal bovine acellular dermal matrix, in
healing chronic diabetic foot ulcers: a prospective multicenter study. Adv Skin Wound Care. Aug 2014;
27(8):356-362. PMID 25033310
56. Karr JC. Retrospective comparison of diabetic foot ulcer and venous stasis ulcer healing outcome between a
dermal repair scaffold (PriMatrix) and a bilayered living cell therapy (Apligraf). Adv Skin Wound Care. Mar
2011; 24(3):119-125. PMID 21326023
57. Falanga V, Margolis D, Alvarez O, et al. Rapid healing of venous ulcers and lack of clinical rejection with an
allogeneic cultured human skin equivalent. Human Skin Equivalent Investigators Group. Arch Dermatol.
Mar 1998; 134(3):293-300. PMID 9521027
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58. Harding K, Sumner M, Cardinal M. A prospective, multicentre, randomised controlled study of human
fibroblast-derived dermal substitute (Dermagraft) in patients with venous leg ulcers. Int Wound J. Apr
2013; 10(2):132-137. PMID 23506344
59. Mostow EN, Haraway GD, Dalsing M, et al. Effectiveness of an extracellular matrix graft (OASIS Wound
Matrix) in the treatment of chronic leg ulcers: a randomized clinical trial. J Vasc Surg. May 2005; 41(5):837843. PMID 15886669
60. Romanelli M, Dini V, Bertone M, et al. OASIS wound matrix versus Hyaloskin in the treatment of difficult-toheal wounds of mixed arterial/venous aetiology. Int Wound J. Mar 2007; 4(1):3-7. PMID 17425543
61. Romanelli M, Dini V, Bertone MS. Randomized comparison of OASIS wound matrix versus moist wound
dressing in the treatment of difficult-to-heal wounds of mixed arterial/venous etiology. Adv Skin Wound
Care. Jan 2010; 23(1):34-38. PMID 20101114
62. Serena TE, Carter MJ, Le LT, et al. A multicenter, randomized, controlled clinical trial evaluating the use of
dehydrated human amnion/chorion membrane allografts and multilayer compression therapy vs.
multilayer compression therapy alone in the treatment of venous leg ulcers. Wound Repair Regen. Nov-Dec
2014; 22(6):688-693. PMID 25224019
63. Serena TE, Yaakov R, DiMarco D, et al. Dehydrated human amnion/chorion membrane treatment of venous
leg ulcers: correlation between 4-week and 24-week outcomes. J Wound Care. Nov 2015; 24(11):530-534.
PMID 26551645
64. Fivenson DP, Scherschun L, Cohen LV. Apligraf in the treatment of severe mitten deformity associated with
recessive dystrophic epidermolysis bullosa. Plast Reconstr Surg. Aug 2003; 112(2):584-588. PMID 12900618
65. Clare G, Suleman H, Bunce C, et al. Amniotic membrane transplantation for acute ocular burns. Cochrane
Database Syst Rev. 2012; 9:CD009379. PMID 22972141
66. Adly OA, Moghazy AM, Abbas AH, et al. Assessment of amniotic and polyurethane membrane dressings in
the treatment of burns. Burns. Aug 2010; 36(5):703-710. PMID 20004061
67. Carsin H, Ainaud P, Le Bever H, et al. Cultured epithelial autografts in extensive burn coverage of severely
traumatized patients: a five year single-center experience with 30 patients. Burns. Jun 2000; 26(4):379-387.
PMID 10751706
68. Lagus H, Sarlomo-Rikala M, Bohling T, et al. Prospective study on burns treated with Integra(R), a cellulose
sponge and split thickness skin graft: comparative clinical and histological study--randomized controlled
trial. Burns. Dec 2013; 39(8):1577-1587. PMID 23880091
69. Branski LK, Herndon DN, Pereira C, et al. Longitudinal assessment of Integra in primary burn management:
a randomized pediatric clinical trial. Crit Care Med. Nov 2007; 35(11):2615-2623. PMID 17828040
70. Heimbach DM, Warden GD, Luterman A, et al. Multicenter postapproval clinical trial of Integra dermal
regeneration template for burn treatment. J Burn Care Rehabil. Jan-Feb 2003; 24(1):42-48. PMID 12543990
71. Still J, Glat P, Silverstein P, et al. The use of a collagen sponge/living cell composite material to treat donor
sites in burn patients. Burns. Dec 2003; 29(8):837-841. PMID 14636761
72. Lukish JR, Eichelberger MR, Newman KD, et al. The use of a bioactive skin substitute decreases length of
stay for pediatric burn patients. J Pediatr Surg. Aug 2001; 36(8):1118-1121. PMID 11479839
73. Amani H, Dougherty WR, Blome-Eberwein S. Use of Transcyte and dermabrasion to treat burns reduces
length of stay in burns of all size and etiology. Burns. Nov 2006; 32(7):828-832. PMID 16997480
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74. Davidson A, Jina NH, Marsh C, et al. Do functional keratin dressings accelerate epithelialization in human
partial thickness wounds? A randomized controlled trial on skin graft donor sites. Eplasty. 2013; 13:e45.
PMID 24058716
75. Helgeson MD, Potter BK, Evans KN, et al. Bioartificial dermal substitute: a preliminary report on its use for
the management of complex combat-related soft tissue wounds. J Orthop Trauma. Jul 2007; 21(6):394-399.
PMID 17620998
76. Taras JS, Sapienza A, Roach JB, et al. Acellular dermal regeneration template for soft tissue reconstruction
of the digits. J Hand Surg Am. Mar 2010; 35(3):415-421. PMID 20138715
77. Weigert R, Choughri H, Casoli V. Management of severe hand wounds with Integra(R) dermal regeneration
template. J Hand Surg Eur Vol. Mar 2011; 36(3):185-193. PMID 21078866
78. Lazic T, Falanga V. Bioengineered skin constructs and their use in wound healing. Plast Reconstr Surg. Jan
2011; 127 Suppl 1:75S-90S. PMID 21200276
79. Saffle JR. Closure of the excised burn wound: temporary skin substitutes. Clin Plast Surg. Oct 2009;
36(4):627-641. PMID 19793557
80. American Society of Plastic Surgeons. Evidence-Based Clinical Practice Guideline: Breast Reconstruction
with Expanders and Implants. 2013; http://www.plasticsurgery.org/Documents/medicalprofessionals/health-policy/evidence-practice/breast-reconstruction-expanders-with-implantsguidelines.pdf. Accessed November, 2014.
81. Hopf HW, Ueno C, Aslam R, et al. Guidelines for the treatment of arterial insufficiency ulcers. Wound Repair
Regen 2006; 14(6)693-710. 2007/01/04:http://www.plasticsurgery.org/For-MedicalProfessionals/Legislation-and-Advocacy/Health-Policy-Resources/Endorsed-Guidelines-Developed-byOther-Medical-Societies/Wound-Healing-Society-.html. Accessed November, 2014.
82. Robson MC, Cooper DM, Aslam R, et al. Guidelines for the treatment of venous ulcers. Wound Repair
Regen 2006; 14(6):649-62. 2006; 2007/01/04:http://www.plasticsurgery.org/For-MedicalProfessionals/Legislation-and-Advocacy/Health-Policy-Resources/Endorsed-Guidelines-Developed-byOther-Medical-Societies/Wound-Healing-Society-.html. Accessed November, 2014.
83. Steed DL, Attinger C, Colaizzi T, et al. Guidelines for the treatment of diabetic ulcers. Wound Repair Regen
2006; 14(6):680-92. 2006; 2007/01/04:http://www.plasticsurgery.org/For-MedicalProfessionals/Legislation-and-Advocacy/Health-Policy-Resources/Endorsed-Guidelines-Developed-byOther-Medical-Societies/Wound-Healing-Society-.html. Accessed November, 2014.
84. American Society of Plastic Surgeons (ASPS). Evidence-based Clinical Practice Guideline: Chronic Wounds of
the Lower Extremity. 2007; http://www.plasticsurgery.org/Documents/medical-professionals/healthpolicy/evidence-practice/Evidence-based-Clinical-Practice-Guideline-Chronic-Wounds-of-the-LowerExtremity.pdf. Accessed November, 2014.
85. National Institute for Health and Care Excellence (NICE). NICE Clinical Guideline NG19. Diabetic Foot
Problems: Prevention and Management. 2015; https://www.nice.org.uk/guidance/ng19/evidence.
Accessed December 22, 2015.
86. Frykberg RG, Zgonis T, Armstrong DG, et al. Diabetic foot disorders. A clinical practice guideline (2006
revision). J Foot Ankle Surg 2006; 45 (5 Suppl):S1-66.
http://www.acfas.org/uploadedFiles/Healthcare_Community/Education_and_Publications/Clinical_Practic
e_Guidelines/DiabeticCPG-small.pdf. Accessed November, 2014.
87. Lipsky BA, Berendt AR, Cornia PB, et al. 2012 Infectious Diseases Society of America clinical practice
guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012 Jun; 54(12):e132Page 28 of 29
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173. 2012; http://www.idsociety.org/uploadedFiles/IDSA/GuidelinesPatient_Care/PDF_Library/2012%20Diabetic%20Foot%20Infections%20Guideline.pdf. Accessed November,
2014.
88. Centers for Medicare and Medicaid Services (CMS). Porcine skin and gradient pressure dressing. 270.5.
http://www.cms.gov/medicare-coverage-database/details/ncddetails.aspx?NCDId=139&ncdver=1&bc=AgAAQAAAAAAA&. Accessed November, 2014.
89. Centers for Medicare and Medicaid Services (CMS). CMS issues hospital outpatient department and ambulatory surgical center policy and payment changes for 2014. 2013;
http://www.cms.gov/Newsroom/MediaReleaseDatabase/Fact-Sheets/2013-Fact-Sheets-Items/2013-11-273.html. Accessed November, 2014.
90. National Government Services, Inc. Local Coverage Determination (LCD): Biologic Products for Wound
Treatment and Surgical Interventions (L33391). Revision effective date for services performed on or after
6/01/16.
91. National Government Services, Inc. Local Coverage Article: Dermagraft® – Related to LCD L33391 (A52387).
Revision Effective Date 10/01/2015.
92. National Government Services, Inc. Local Coverage Article: EpiFix® - Related to LCD L33391 (A52388).
Revision Effective Date 10/01/2015.
93. National Government Services, Inc. Local Coverage Article: Apligraf® – Related to LCD L33391 (A52389).
Revision Effective Date 10/01/2015.
94. National Government Services, Inc. Local Coverage Article: OASIS® Wound Matrix and OASIS® Ultra TriLayer Matrix – Related to LCD L33391 (A52392). Revision Effective Date 10/01/2015.
95. National Government Services, Inc. Local Coverage Article: PriMatrix™ Dermal Repair Scaffold - Related to
LCD L33391 (A52396). Revision Effective Date 10/01/2015.
96. National Government Services, Inc. Local Coverage Article: AlloDerm® Regenerative Tissue Matrix – Related
to LCD L33391 (A52401). Revision Effective Date 10/01/2015.
97. National Government Services, Inc. Local Coverage Article: GRAFTJACKET® Regenerative Tissue MatrixUlcer Repair and GRAFTJACKET® XPRESS Flowable Soft Tissue Scaffold – Related to LCD L33391 (A52410).
Revision Effective Date 1/01/2016.
98. National Government Services, Inc. Local Coverage Article: TheraSkin® – Related to LCD L33391 (A52411).
Revision Effective Date 10/01/2015.
99. National Government Services, Inc. Local Coverage Article: Integra® Dermal Regeneration Template
(IDRT)/Integra® Omnigraft™ Dermal Regeneration Matrix (Omnigraft™) and Integra® Bilayer Wound
Dressing – Related to LCD L33391 (A52418). Revision Effective Date 6/01/2016.
100. National Government Services, Inc. Local Coverage Article: Grafix® - Related to LCD L33391 (A54057).
Revision Effective Date 10/01/2015.
101. National Government Services, Inc. Local Coverage Article: HYALOMATRIX® Wound Device - Related to LCD
L33391 (A54707). Revision Effective Date 11/01/2015.
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