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Branski
Branski
available at www.sciencedirect.com
Article history: Introduction: Autograft take and rapid wound closure is essential for the survival of severely
Accepted 9 August 2009 burned patients. Loss of skin grafts typically occurs during the first few days after coverage,
mainly due to shear forces and inadequate contact with the wound bed. Slow-clotting fibrin
Keywords: sealant, applied with a spray-on device, has been shown to improve healing of skin grafts in
Pig large wounds. However, its use in burn wounds has not been studied so far.
Wound healing Study aim: To evaluate the effectiveness of sprayed fibrin sealant in excised and grafted full-
Autograft thickness burns.
Skin substitute Material and methods: Ten female Yorkshire pigs (30–45 kg) received a full-thickness contact
burn of approximately 15% total body surface area. The burns were excised to the level of the
muscular fascia after 24 h and covered with meshed skin autograft (mesh ratio 1:3). Wounds
were randomized to either fibrin sealant (n = 20) or standard skin staples (n = 16) for graft
fixation. Fibrin sealant was used as a slow-clotting spray (4 IU thrombin/ml). Outcome
measurements included clinical scoring at days 2, 5, 9 and 14 postoperatively, planimetric
analysis of wound closure, and histological examination of epidermal and dermal thickness
14 days after autografting.
Results: In the fibrin sealant group, graft adherence scores were significantly increased
( p < 0.02) and graft dislocation scores significantly decreased ( p < 0.01) at days 2 and 5
postoperatively, when compared to controls. Planimetric analysis of remaining open mesh
interstices showed acceleration of wound closure in the fibrin sealant group but did not
reach statistical significance (day 14 p = 0.04 at significance level p < 0.025). Wound contrac-
tion, occurrence of hematoma, and dermal as well as epidermal thickness were not different
between the groups at 14 days postoperatively.
Conclusion: The results indicate that the use of slow-clotting fibrin sealant spray for auto-
graft fixation is advantageous over skin staples. Easy handling and reduced graft dislocation
at early time points are key qualities of this method.
# 2011 Published by Elsevier Ltd and ISBI.
* Corresponding author at: Sunnybrook Health Sciences Centre, Department of Surgery, Division of Plastic Surgery University of Toronto,
Sunnybrook Research Institute, Rm D704, 2075 Bayview Ave. Toronto, ON, Canada M4N 3M5. Tel.: +1 (416) 480 6703; fax: +1 (416) 480 6763.
E-mail address: marc.jeschke@sunnybrook.ca (M.G. Jeschke).
1
Both authors contributed equally to this manuscript.
0305-4179/$36.00 # 2011 Published by Elsevier Ltd and ISBI.
doi:10.1016/j.burns.2009.08.011
burns 37 (2011) 1360–1366 1361
100%
10%
20%
40%
65%
surrounding tissue
autograft. Wounds are excised to the level of muscle
fascia. (B) Application of meshed skin autograft with the
application of fibrin sealant.
dressing changes, heart rate and oxygen saturation were
not viable
not viable
and evaluated using planimetric software. For correct mea-
None
surement of the absolute area of each parameter by
planimetry, a calibrated benchmark was positioned adjacent
to each wound site during photographing.
Grade
Clinical evaluation of wounds was conducted using a scale
0
1
5
from 0 to 5. Parameters of the clinical evaluation included graft
burns 37 (2011) 1360–1366 1363
adherence, graft dislocation, granulation tissue level, occur- Remaining Open Wound Area
Fibrin Sealant
50%
rence of hypergranulation and hematoma, and fibrin deposi- Staples
3. Results *
0.0
Graft Dislocation Graft Adherence
3.1. Wound healing and re-epithelialization
2.0
Table 3 – Measurements of dermal and epidermal thickness. Data are presented as means W standard deviation.
Fibrin sealant (n = 12) [mm] Staples (n = 12) [mm] p
Dermis Wound center 4109 1415 3806 1227 ns
Wound edge 4702 504 3856 1515 ns
Normal tissue 2440 546 2501 133 ns
Epidermis Wound center 177 45 163 41 ns
Wound edge 277 124 247 123 ns
Normal tissue 103 29 104 17 ns
interstices were 1.7% lower with FS than with staples after 14 3.3. Histology
days (Fig. 2).
In the histological evaluation, we did not observe differences
3.2. Clinical evaluation in the thickness of epidermis or dermis between the study
groups (Table 3). In the H&E staining, both groups showed the
Using the clinical scale for wound assessment of graft typical pattern of rete ridges and papillary dermis (Fig. 4). A
dislocation and graft adherence (Table 1), we found that graft well organized dermal–epidermal junction, that also showed a
adherence was significantly increased in the FS group on days regular, stained basal cell layer, was present in all sections. In
2 and 5. Graft dislocation was correspondingly lower in the FS both groups we saw the fragile, newly formed epidermis over
group on days 2 and 5 (Fig. 3A and B). No significant differences the former mesh interstices, with no difference in epithelial
were noted in the evaluation of granulation tissue level, thickness. In all groups, a similar number of small vessels
occurrence of hypergranulation and hematoma, and fibrin were present underneath the outgrowing epithelial exten-
deposition between the groups. Local infection was noted in sions and within the organizing granulation tissue.
one wound field in each group at day 9.
4. Discussion
excellent tool for the evaluation of therapeutic agents destined healed, as opposed to 92% in the staples group. Both groups
for use in human wounds. showed a similar amount of wound contraction. While this
Only few groups have, however, extended their wound difference in wound healing did not reach statistical difference
healing model to the more complex situation of a burn injury. in this study, we believe that in a severely burned patient, even
Middelkoop et al. [22] introduced a model of partial and full- slightly accelerated wound healing translates into less time in
thickness burn in Yorkshire Swine; Danilenko et al. [23] used the burn unit, less susceptibility to infection, less use of
adult minipigs for burn and excision studies. These studies analgesics, and avoidance of further reconstructive surgery.
showed the general applicability of porcine burn wound Taking into account the immense costs of burn treatment, every
models. Only Singer and McClain [24] standardized a porcine day less in the burn ICU is also an important economic factor.
burn and autograft model. Mittermayr et al. [11] developed a We did not see any significant differences in the occurrence
porcine wound excision model and tested the use of fibrin of hematoma in this study and attribute this to good operative
sealant. For the use in further wound healing studies, our technique and the fact that the study was conducted by only
group has recently developed a reliable and reproducible two surgeons who had experience with this animal model.
model of burn, excision and autografting [12]. The even level of granulation tissue indicates a healthy wound
We chose two groups according to the clinical situation: healing which is not influenced by systemic factors. Finally,
skin staples are the method of choice for the fixation of hypergranulation did only occur in some wound fields where
autografts in the severely burned patient, as large wound partial graft loss was present, but there were no differences
surfaces have to be covered in a timely fashion. They served between the study groups.
as controls in our study. Fibrin sealant was the test There are some limitations to this study. Wound fields of
substance. Its slow-clotting version and the application of 50 cm2 cannot be directly translated to severely burned patients,
a thin layer of fibrin sealant (0.05 ml/cm2) have been shown where large areas of the skin are burned and wound healing is
effective in both human [15,25] and porcine [11] studies. generally compromised by the systemic response. A porcine
Moreover, spray application of fibrin sealant results in an model of delayed wound healing (aged or diabetic pig) may have
equal ratio of thrombin and fibrinogen, and facilitates the more clearly demonstrated the advantage of wound healing
formation of a homogenously thin fibrin layer [26]. We have acceleration with fibrin sealant or whether it needs addition of
previously shown that the specific fibrin sealant (TisseelTM) growth factors to further improve healing like in other models
used in this study (physiological coarse type fibrin sealant) is [30]. Finally, an extended observation period would have
superior to the fine type fibrin sealant and to autologous shown the effect of FS on scarring and graft stability.
sealants [14,27]. Graft fixation with slow clotting, coarse type fibrin sealant
Our main finding is the improved handling and reduced is an adequate alternative for skin staples. Our findings
graft dislocation/increased adherence in the fibrin sealant indicate that graft adherence improved and graft dislocation
group. We observed a significantly higher level of graft minimized. The application of only 0.05 ml/cm2 FS with an
adherence, and, correspondingly, less graft dislocation in advanced spraying device also facilitates handling. We
the FS group. This significant difference is visible at postoper- achieved these results in a porcine model of full-thickness
ative days 2 and 5, and clearly indicates that the application of burn that is similar to the clinical situation in humans. Thus,
fibrin sealant provides better graft attachment to the wound the use of FS in the fixation of split-thickness skin autografts
surface than skin staples. When skin staples are used for the on excised burn wounds can be recommended.
fixation of widely meshed autografts, only one strand of the
mesh can be grasped with each staple, making the graft nets
even more prone to graft loss than sheet grafts. Graft loss even Conflict of interest
occurs when large amounts of staples are used, appropriate
pressure dressings are applied, and experienced surgeons HR is a consultant to Baxter Innovations, Vienna.
conduct the operation. The main reason for the loss is that a
continuous contact of graft and recipient bed cannot be
guaranteed. Graft loss occurs mainly during the first three Acknowledgements
postoperative days, and particularly when placed in exposed
anatomical locations [28]. The application of thin layers of We would like to acknowledge the entire staff of the large
fibrin sealant does not only provide complete contact between animal facility of the Shriners Hospital for Children, especially
wound bed and graft, but also acts as a scaffold for collagen Thomas Miszalkiewski and John R. Salsbury, for their great
producing fibroblasts, provides a matrix for vascularization, support in the conduction of the animal studies. We also want
and possibly creates a barrier against infection [10,29]. to thank Zafar Khakpour, LBI Vienna, for the design and
Therefore, we believe that the advantage of a good graft construction of the burn apparatus, and Pat Sellers of the
adherence and re-vascularization in the early postoperative Pathology core lab for the preparation of histological slides.
phases translates into an accelerated wound closure in the We would like to thank Dipl.-Math. John-Philip Lawo for the
late phase, and represents a strong argument for the use of statistical analysis of the planimetric data as well as Andreas
fibrin sealant in the fixation of widely meshed autografts. Goppelt, Ph.D., Johannes Regenbogen, Ph.D., Sabine Fraiss,
A significant acceleration in re-epithelialization, repre- Ph.D. and Melitta Bilban, Ph.D. for the support and valuable
sented by a reduction of remaining open wound area, could discussions. The work was supported by a Shriners Hospital
not be observed in this study. At day 14, the last day of our for Children Research Fellowship Grant and an unrestricted
observation, 94% of the initial open wound in the FS group was research grant by Baxter AG Vienna.
1366 burns 37 (2011) 1360–1366