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Journal of Plastic, Reconstructive & Aesthetic Surgery (2008) xx, 1e6

Delayed skin allograft rejection following
matrix membrane pretreatment*
Bart M. Stubenitsky a,*, Lauren Brasile b, Lorita M. Rebellato c,
Harm Hawinkels d, Carl Haisch e, Moshe Kon a
a

UMCU, Department of Plastic Reconstructive Surgery, Utrecht, The Netherlands
BREONICS Inc,Otisville, NY, USA
c
ECU, Department of Pathology, Greenville, NC, USA
d
AZM, Department of Plastic Reconstructive Surgery, Maastricht, The Netherlands
e
ECU, Department of Surgery, Greenville, NC, USA
b

Received 28 May 2006; accepted 4 December 2007

KEYWORDS
Skin transplantation;
Immunomodulation;
Immunocloaking;
Graft rejection;
Delayed rejection;
Graft pretreatment

SummaryIntroduction: No solution has been offered to induce long-term skin allograft
survival in burn patients. We investigated whether transplant acceptance could be improved
by a nonsystemic pretreatment of the graft and recipient wound surfaces with a bioengineered
interface consisting of an acellular matrix membrane.
Methods: Group 1 (n Z 30): Crosstransplants of untreated skin grafts between BALB/c andC57BL/6 mice.
Group 2 ( n Z 30): Crosstransplants of matrix-treated skin grafts between BALB/c and
C57BL/6 mice.
Group 3 (n Z 30): Retransplantation of skin grafts from the original donor on to the sensitised recipients. Sensitisation was accomplished by prior transplantation of an untreated skin
allograft from the same donor (Group 1 mice).
Two skin grafts were transplanted: one treated andone untreated.
Results: Rejection occurred in the untreated group after a mean of 6.8 days (Æ1.5 days). In
contrast, treatment with the bioengineered matrix membrane was found to substantially prolong allograft survival with a mean of 28 days (Æ3.8 days). Graft survival between the two
groups reached statistical significance (P < 0.05). In the sensitised mice, the untreated skin
regrafts wereall rejected in an accelerated fashion with an onset of less than 4 days (mean Æ 1
days). However, the matrix membrane-treated skin regrafts were maintained for a mean of 18
days (Æ3 days).
Conclusion: These results show that treatment with the bioengineered matrix membrane
greatly delays the onset of acute allograft rejection. The described topical application to

*

Presented at EURAPS2003 and NVPC 2003.
* Corresponding author. Address: UMCU, Department of Plastic and Reconstructive Surgery, Postbus 85500, 3508 GA Utrecht, The
Netherlands. Tel.: þ31 30 2506954; fax: þ31 30 2516097.
E-mail address: bartsky@gmail.com (B.M. Stubenitsky).
1748-6815/$ - see front matter ª 2007 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and AestheticSurgeons.
doi:10.1016/j.bjps.2007.12.001

Please cite this article in press as: Bart M Stubenitsky et al., Delayed skin allograft rejection following matrix membrane pretreatment, J
Plast Reconstr Aesthet Surg (2008), doi:10.1016/j.bjps.2007.12.001

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B.M. Stubenitsky et al.
the wound surfaces of both the graft and the recipient may offer a new and readilyavailable
source of wound coverage in patients with extensive burns.
ª 2007 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and
Aesthetic Surgeons.

Extensive burns represent one of the most devastating
injuries to the human body. Severe, deep burns cause fluid
escape, loss of temperature control, disturbances of ion
equilibrium, and high risk ofbacterial invasion. Treatment
of such injury requires skin replacement to reform the
functional and protective barrier that differentiated epidermis provides. Next to using autologous skin, which is
often impossible in patients with large acute wounds due to
the lack of adequate donor sites, the best option is allograft
skin. For deep extensive burns, temporary closure can be
achieved with a...