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32 Use ofPorcine Urinary Bladder Matrix (UBM-ECM) intheHead andNeck Region
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defect must be removed from the exposed wound
regions before stable healing occurs.
ECM wound device therapy usually needs a
secondary dressing that can be as simple as a
head wrap or cap, silicone sheets, or sutured
dressings. We have found shaving a 3–4cm rim
of hair around scalp wound helps with both keeping the wound clean and allowing for placement
of a polyurethane sheet dressing which allows for
retention of sufcient moisture to facilitate the
constructive remodeling healing response.
Alternatively, one can keep the device hydrated
with a hydrogel with a secondary Telfa-type
overlying dressing. One needs to be sure that the
device has adequate hydration and should it
appear too dry or healing is slowed, a trial of
placing increased moisture should be tried before
a further treatment.
Over the last 6years, we have been using the
UBM-ECM device; we have evolved in our
thinking and utilization of the wound device.
Initially we began using it much like other topical
wound therapies only to appreciate that larger
amounts of the device could be successfully
applied at one setting, so we moved to placing
multiple device formulations at the time of the
initial operative wound bed preparation. The subsequent care was simplied as it only required
placement of small amounts of hydrogel on top
of a secondary dressing which caused little
patient pain and discomfort. Suturing the device
into the wound either directly or with a secondary
dressing sutured at the margins has also facilitated postoperative care. The wound is then
observed until it is healed or until the wound has
lled in to a point a simple skin graft is possible.
UBM-ECM wound device healing occurs via
a process referred to as constructive remodeling
which occurs when the wound device is broken
down at the wound bed surface and replaced with
the host’s native tissue(s). This newly formed tissue is typically a very close replica of the missing
tissue, but as it is not identical to the missing tissue, it is improper to refer to this healing process
as regeneration. Newly generated peptide fragments referred to as matricryptins, matrikinins,
or matricryptic peptides which form as the host
cells degrade the ECM device exert potent bioactivity with their newly exposed adhesions sites
[27, 28]. These shorter fragments often have biologic responses that are distinct from, and often
more potent than, those of the native parent molecule. It is the combination of all of these newly
formed peptides which regulate the wide variety
of injury and healing processes observed including angiogenesis, anti-angiogenesis, migration,
differentiation, adhesion, as well as the associated antimicrobial activity that yields the less
scarred constructive remodeling healing
observed. A recent publication [29] is the most
complete characterization of the composition of
the EBM-ECM wound device and highlights the
enhanced M-2 macrophage healing response
noted in previous studies [30-32]. Over 500 proteins were identied via mass spectrometry, with
78% identied as MatriSome and MatriSomeassociated proteins (Fig.32.1). Sadtler etal. [29]
found that within the MatriSome category of proteins (77% of total), 98% were collagens (especially Types 1, 3–6, and 14), 1% ECM
glycoproteins, and 1% proteoglycans. Within the
MatriSome-associated fraction (1% of total),
55% were ECM regulators, 44% were ECM afliated proteins, and 2% were secreted factors. The
most abundant non-MatriSome proteins included
actin, desmin, and hemoglobin. Additionally,
adaptive immune T and B cells were also detected
suggesting a role for antigen specicity to the
remodeling response. What is clear is that a
deeper understanding of all of the ECM components and their interactions with the body’s
immune system is needed to develop best practice UBM-ECM device use.
Clinically we have noted the normal inammatory healing response is also greatly reduced
as patients experience less swelling, scarring, and
pain in the treated regions both early on and in
the long term. We have not observed the restoration of skin appendages; however the UBM-ECM
wound device provides a healthy healed wound
which is amenable to later hair follicle grafting
procedures.
Mohs surgical management of skin cancers of
the head and neck has become more common-
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B. A. Kraemer and A. G. Rowe
ab
cd
Fig. 32.1 UBM-ECM Formulations. (a) The freeze-
dried formulation of the UBM-ECM is available as a duallayer lyophilized sheet wound device (Cytal
Matrix) or ground into a powder (MicroMatrix
ing powder). (b) Scanning electron micrograph of the
lyophilized (freeze-dried) sheet shows the natural ECM
matrix structure after complete decellularization. Note
both the overlying intact smooth surface of the intact
basement membrane layer and the honeycombed ECM
®
Burn
®
, overly-
place, and with micrographic margin control, the
use of the ECM wound devices can have great
utility. The use of an ECM wound device at the
time that clear margins are obtained can help
limit the scarring. Many Mohs surgeons now also
perform their own wound closures and refer only
the larger more complex patients for treatment.
Forehead aps are a mainstay of treatment of
large nasal defects. Patient acceptance of the procedure can be an obstacle for the medically ill,
the anticoagulated patient, and the younger
patient who doesn’t want to have a two-stage, let
matrix structure which optimally presents the ECM constituents for host tissue interaction. (c) The thicker fenestrated vacuum-pressed sheet formulation marketed as a
3- or 6-layer Cytal
micrograph of the vacuum-pressed 6-layer sheet demonstrating the denser, compressed ECM matrix. These formulations persist in the wound bed the longest with the
6-layer device lasting the longest
®
Wound Matrix. (d) Scanning electron
alone a three-stage, ap reconstructive procedure. We have also used the UBM-ECM device
to manage a large nasal sidewall defect down to a
smaller-sized alar rim defect which was amenable to a free ear cartilage-skin graft. A close
working relationship with dermatologists is additionally useful for co-managing unusual inammatory and healing issues of the scalp. We have
treated two cases of pustular dermatosis with
UBM-ECM which optimally responded to thalidomide treatment in one case and the second
one which responded to FK-506.
32 Use ofPorcine Urinary Bladder Matrix (UBM-ECM) intheHead andNeck Region
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Acute trauma degloving-type wounds can
lead to large surface wound. These wounds typically heal well, but at the time of acute injury,
patients want to be sure that all measures are
taken to minimize scarring. For crush nasal or
nasoorbitalethmoidal injuries, we have used the
device in a single or multi-layer formulation
depending upon the degree of injury for internal
nasal lining and preservation of the nasal cavity.
The high collagen content of the device also acts
as a hemostatic agent to control the inevitable
bleeding.
UBM-ECM wound devices are clinically
available in three formulations, and an understanding of the performance characteristics of
each formulation allows for the enhanced healing
possible:
1. The MicroMatrix® powder (Fig. 32.1) pro-
duces a more rapid, robust healing response
as the small particle size allows for rapid
breakdown. It can be applied as a direct pow-
der or mixed with saline to create a thick
slurry for injection. It can be used serially
with alternate day treatments or in large vol-
umes in a single placement. We have found it
useful to improved healing (“take”) of skin
grafts in wounds beds that are less than ideal
or in patients who are poor surgical
candidates.
2. The lyophilized sheet formulation (Fig.32.1)
is the device formulation prior to it being
ground into powder and has a more sustained
response over the period of 1week or more as
a single sheet or longer if it is “packed” into a
wound.
3. The vacuum-pressed sheets (Fig. 32.1) are
available in 3-layer and 6-layer sheet formula-
tions as Cytal
®
Surgical Sheets. There is also
an 8-layer sheet available as Gentrix® Surgical
Thick sheets which is indicated for tissue reinforcement such as in hernia repair. We have
found the suture-holding capacity of the vacuum-pressed sheets useful to secure the skin
margins of an open wound, reduce skin closure tension as well as help to hold and retain
other formulations of the UBM-ECM device
placed deeper in the wound.
One of the greatest present limitations to
UBM-ECM use comes from insurance companies classifying these devices as experimental
and denying coverage. Also, there is limited
reimbursement for outpatient use, so all of the
cases in this series had the device placed in the
operating room. Both of these limitations
should be solved in the near future which will
allow for more timely and rapid healing with
use of these devices. More recently we have
had success appealing the denial decisions
after discussing the case with a medical director who has knowledge of surgery and wound
care.
We found most patient had healed wounds
with good outcomes with the following notes:
1. Scalp and forehead wounds tend to heal
slower and often required several applications
of the device to yield a wound able to be skin
grafted or go on to complete closure.
2. Patients that initially had more aggressive
bone debridement (as discussed) showed
improved healing with fewer treatments.
3. The slowest healing occurred with therapeutic
prior scalp radiation for cancer treatment and
with pustular dermatosis of the scalp (until
treated with tacrolimus– Case 10).
4. The wound device use in improving scar revi-
sions holds great promise.
5. Contracted facial scars did not dramatically
improve with placement of the device under
the intact skin.
6. More research is needed to determine optimal
use of the UBM-ECM wound device.
32.4 Clinical Cases
These clinical cases represent an evolution of our
clinical experience trying to obtain optimal healing with the various formulations of the UBM-
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B. A. Kraemer and A. G. Rowe
ECM wound device. We found that placing larger
amounts of the device at the operative setting
proved to be both effective and saved patients’
time and discomfort at subsequent follow- up visits. Powder was used more often in treating
chronic wounds to stimulate a robust healing
response in a chronic wound bed. Common to the
management of all of these wounds is securing
the device into the wound bed and the need for
the wound devices to be kept moist with serial
application of hydrogels and/or the use of moisture retentive dressings such as a polyurethane
sheet dressing. Of particular note is the appearance of the lighter pink salmon-colored UBMECM-stimulated granulation tissue which forms
(Figs.32.2d, 32.3g, 32.8e, 32.9g, and 32.9h) and
the formation of visible blood vessels in the
newly formed tissue (Fig. 32.2j).
ab
cd
Fig. 32.2 A 65-year-old male having had a wide resection of stage 2 nodular melanoma of his left temple closed
with a full-thickness skin graft, subsequent radiation therapy followed by a methicillin-resistant Staphylococcus
aureus infection leading to this exposed bone open wound
for 2 years. (a) Initial appearance of the left temple
wound. (b) Wound after debridement of the outer necrotic
bone. (c) Wound after placement of MicroMatrix
and Cytal
tially close wound and retain the wound device in the
wound bed. (d) Wound 3 weeks postoperative. (e) Wound
®
Burn Matrix and Prolene sutures placed to par-
®
powder
7 weeks postoperative at time of repeat full-thickness skin
graft. (f) Wound 2 weeks post-grafting. (g) Wound 6
weeks post-grafting. (h) Twelve weeks post-grafting,
additional MicroMatrix
weeks post-grafting nearly healed. (j) Five months later,
debrided and additional MicroMatrix
(k) Two months later, and after additional MicroMatrix
powder application the wound then heals—note the
appearance of new blood vessels in the wound bed. (l)
One year later. (m) Two years later
®
powder applied. (i) Fourteen
®
powder applied.
®
32 Use ofPorcine Urinary Bladder Matrix (UBM-ECM) intheHead andNeck Region
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ij
Fig. 32.2 (continued)
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B. A. Kraemer and A. G. Rowe
k
m
l
Fig. 32.2 (continued)
32.4.1 Forehead andScalp
Initial management of this patient required
removal of the obviously necrotic exposed bone
prior to the placement of both MicroMatrix®
powder and Cytal® Burn Matrix (Fig.32.2). The
device was retained in the wound with Prolene
sutures used to partially close the circular as well
as retain the wound device in the wound bed like
a mesh. The healing was slow with several small
foci of bone which failed to promote healing and
needed removal. Of particular interest was the
formation of visible new blood vessels which
formed during the healing process. Integra® was
not employed in this case due to the risk of infection in this chronic wound.
This patient who sustained a nearly fatal
stroke had a poorly treated, infected, fullthickness skull defect with exposed, injured dura
(Fig.32.3). The dura repair device, while classi-
cd
32 Use ofPorcine Urinary Bladder Matrix (UBM-ECM) intheHead andNeck Region
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a
b
ef
Fig. 32.3
A 42-year-old female with a scalp wound following a decompressive craniotomy for a major right
middle cerebral artery stroke. (a, b) Initial wound appearance showing exposed central cranial bone edge and poor
wound care. (c, d) CT scan showing the calvarial bone
defect and the Durepair
®
dura regeneration matrix (bright
wavy line in d) used for dural closure/reinforcement. (e)
Debrided wound with bone debrided back to bleeding and
the dural edge present just above the hooks—no CSF leak
was noted. (f) After placement of MicroMatrix
and Cytal
®
6-layer vacuum pressed sheet placement. (g)
Four weeks postoperative showing residual ECM device
still present in the wound. (h) Ten weeks postoperative
with a region of bone still exposed. (i) One month after
bone debridement and placement of additional
MicroMatrix
®
powder. (j) Seven months later (11 months
after initial procedure). (k) After neurosurgery replaced
bone ap 7 months later
®
powder
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B. A. Kraemer and A. G. Rowe
i
j
k
Fig. 32.3 (continued)
ed as an ECM device, is processed for strength
and durability which enhances the tensile dural
repair but alters the native device molecules, so it
problems and possible dermatology consultation for unexpected complications with normal
expected healing.
lacks the enhanced ECM wound healing response
found with the UBM-ECM. Both the
MicroMatrix® powder and Cytal® 6-layer
Surgical Matrix was placed and closed into the
wound with a small open gap treated with daily
hydrogel. The initial debridement of the outer
calvarial bone was inadequate and required additional debridement and placement of the UBMECM for nal closure.
This chronic exposed skull wound which
responded to debridement, ECM treatment, and
subsequent skin grafting failed to completely
heal until being treated with topical tacrolimus
(Fig. 32.4). A large volume of MicroMatrix
powder is placed on top of several layers of the
Cytal® Burn Matrix which was then secured at
the periphery with staples. Once the granulation bed developed to a point it was felt the
wound bed would support a skin graft, a graft
was placed. Medically complex patients such as
this elderly patient with rheumatoid arthritis
require maximal medical management of all
32.4.2 Nasal Reconstruction
The Cytal® Burn Matrix treatment of a degloving
nasal tissue laceration and externally, was done in
an attempt to limit the potential scarring of the
nose (Fig.32.5). Powder was not used due to the
acute nature of the injury and the desired UBMECM healing response was desired for the rst
2 weeks. The UBM-ECM device was employed
due to the severity of the wounds and to avoid
potential secondary internal nasal scarring which
®
is most difcult to treat once it develops. This
patient reported normal breathing and near normal
sensation of the degloved nasal skin. Of particular
interest is the healing of the non-treated brow
region sites which developed some contracted
healing (which might best have been treated with a
wound sheet underlay these aps also).
The UBM-ECM device was used in an attempt
to minimize forehead ap pedicle inammation
32 Use ofPorcine Urinary Bladder Matrix (UBM-ECM) intheHead andNeck Region
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and distal ap swelling, thus allowing for a twostage instead of a standard three-stage forehead
ap nasal reconstruction (Fig. 32.6). We have
also successfully used this in one additional
patient. A single device formulation was used
due to the acute nature of the surgery and desire
for 2–3weeks of desired activity. Figure32.6c, d
demonstrates the reduction of inammation of a
ab
cd
Fig. 32.4
scalp wound and exposed bone following Mohs surgical
resection of a squamous cell cancer. This wound has been
present for over 4 years, and she has had severe rheumatoid arthritis treated for over 30 years. (a, b) Initial wound
appearance. (c) After necrotic bone debridement and
placement of 200 mg MicroMatrix
Placement of a 7× 10 cm Cytal
An 82-year-old female with an open vertex
®
®
powder. (d)
Burn Matrix sheet. (e)
Four weeks later at time of full-thickness skin graft to the
4.5×5cm wound. (f) Skin graft 1 week later. (g) Four
weeks post-grafting. Note the peri-graft inammation
treated with silver nitrate. (h) Eight weeks post-grafting.
(i) After continued poor healing she was diagnosed with
pustular dermatosis that responded to topical tacrolimus
treatment. (j) Wound remains healed 4 months later
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B. A. Kraemer and A. G. Rowe
ef
gh
i
Fig. 32.4 (continued)
j
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