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Advances in Radiotherapy
& Nuclear Medicine Wound reconstruction with Intergra®

around visible lesions. She was left with a large skin deficit newer dermal substitutes made of chitosan to treat wounds
that was minimized to 4×8 cm via mobilization and with full-thickness skin loss and impaired healing due to
advancement of surrounding skin (Figure 3B), but was not radiation. Wounds treated with chitosan biomaterials
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able to be closed entirely. The resulting defect, however, showed the most re-epithelialization and significantly
was still at increased risk of skin graft failure due to decreased scar formation. These studies were limited,
previous radiation in addition to being contraindicated as however, to trying to identify ways to improve healing rates
final margins were unknown at the time of resection. The in previously radiated wounds.
decision was, therefore, made to apply RDM to improve Irradiated wounds treated with skin grafting, in
the underlying wound bed via creation of a neodermis and particular, have been reported with mixed results. Several
to delay definitive reconstruction until the final margins studies have demonstrated skin graft loss in preoperatively
were confirmed. irradiated wounds. 1,67,68 In one of the earliest studies,

The patient was discharged the 1 day after her extirpative Rudolph et al. applied STSGs to radiation ulcers in
st
surgery and received home VAC changes every 2 – 3 days nine patients and reported a 100% rate of skin graft loss
by a visiting nurse. The silicone layer was removed during (predominantly partial) necessitating additional surgery.
1
the third post-operative week and exhibited complete Partial graft loss occurred in both chronic wounds and
matrix integration. After an additional week of a wound freshly excised ulcers, but skin grafts placed on granulating
VAC, the patient was taken back to the OR for application wounds did perform better. The historically high rate of
of an STSG (Figure 3C) and reapplication of a wound VAC. graft loss has led to flaps being the predominant method of
Five days later, the wound VAC was removed and 100% reconstruction for irradiated wounds. 13,69-74
skin graft survival was observed throughout the following To evaluate the need for adjunctive treatments
year of follow-up (Figure 3D-F). beyond skin graft alone when radiation is applied in the

4. Discussion post-operative period, Tadjalli et al. evaluated skin graft
integrity after post-operative external beam irradiation.
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The potential for dermal regeneration templates to assist in In this experiment, rats received different doses of radiation
the healing of a variety of different wounds is well known 4 weeks after graft reconstruction. The rats were then
and documented. These extracellular matrix products assessed for an additional 4 weeks. The authors concluded
have allowed for significant advancements in the field of that post-operative, unfractionated irradiation can induce
regenerative medicine and allowed the plastic surgeon to skin graft loss and ulceration at doses of 25 Gy or higher.
further pursue the principle of replacing like with like. This This suggests that skin graft alone may not be advisable
principle explains the desire to truly recreate tissue that when post-operative radiation is certain or even possible.
has been lost as exemplified using it over exposed active Limited investigations of skin grafting, however,
muscle belly that would potentially allow for survival of have reported better outcomes for irradiated wounds.
a skin graft on its own but would lack the gliding plane Senchenkov et al. reviewed 17 cases of extremity soft tissue
present between muscle and epidermis. The utility of these sarcoma. All wounds had received pre-operative radiation
12
products has, therefore, led to its own rung being added to and were reconstructed with STSGs in conjunction with
the reconstructive ladder in 2010 by Janis et al. Having VAC therapy. Twelve of 17 wounds (71%) healed without
52
helped with other challenging clinical situations, RDMs complication and with greater than 95% of the graft take.
have since gained recognition for their help in irradiated Minor loss (6 – 20% of the graft surface) occurred in three
wounds as well. cases and complete graft loss in two patients. Similarly,
It has been demonstrated that radiated tissue is Kim et al. reported on 25 patients with cicatricial ectropion
vulnerable to developing infection, graft loss, hemorrhage, caused by major cancer ablative surgery and prior radiation
and angiosarcoma. 5,15,21,53-59 This susceptibility toward therapy. Wounds were treated with full-thickness skin
76
higher complications has been demonstrated in grafts. The skin grafts had a viability of 100%, but three
patients treated with radiotherapy both before and after patients required revision surgery.
reconstructive procedures. 60-64
Several studies have reported the results of wounds
In terms of the use of RDMs in irradiated wounds, it treated via Integra RDM followed by skin grafting
was first performed in animal trials. Busra et al. compared Integra® then skin grafting followed by post-operative
monolayer with bilayer tissue-engineered skin substitutes radiation. The Integra® matrix is composed of a two-
applied to radiated rat limbs. The authors concluded that layer skin regeneration system. The outer layer is made of
65
bilayer material is superior to monolayer material in the a temporary silicone epidermal substitute, which protects
treatment of irradiated wound ulcers. Hilmi et al. applied the wound from infection and prevents granulation tissue

Volume 2 Issue 2 (2024) 6 doi: 10.36922/arnm.3388