The buccal fad pad lined with a metabolic active dermal replacement (Dermagraft) for treatment of defects of the buccal plane

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1 The British Association of Plastic Surgeons (2004) 57, The buccal fad pad lined with a metabolic active dermal replacement (Dermagraft) for treatment of defects of the buccal plane J.D. Raguse*, H.J. Gath Clinic for Oral and Maxillofacial Surgery, Charité University Clinic, Augustenburgerplatz 1, Berlin, Germany Received 30 July 2003; accepted 13 May 2004 KEYWORDS Tissue engineering; Head neck cancer; Plastic and reconstructive surgery; Wound healing Summary The buccal fad pad flap (BFPF) is an easy to raise pedicled flap for closure of intraoral defects with barely any donor defect. The major disadvantage of the BFPF is the missing epithelial lining, which can induce fibrous tissue formation with resulting functional impairment. To overcome this problem we lined the BFPF with a dermal replacement (Dermagraft) consisting of living metabolic active fibroblasts. In six patients, defects resulting from tumour removal were reconstructed with a combination of the BFPF and Dermagraft and followed up for at least 2 years. In all patients a defect closure was achieved with no functional impairment. The clinical character which was achieved was more a type of defect regeneration than a flap closure. The availability of bioengineered metabolic active tissue can overcome the major problem of the BFPF as an option for defect closure of the buccal side. Furthermore the regeneration of the defects optimises clinical tumour monitoring. Q 2004 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserved. The buccal plane is a common site for squamous cell carcinomas of the head and neck (SCCHN). After resection of SCC in this area reconstruction of the defects, aims to avoid disturbances of speech, mastication and deglutition. Techniques include the platysma myocutaneous flap (Futrell, 1978), the temporalis muscle flap (Mc Gregor, 1963) or free microsurgical forearm flap (Soutar, 1983). 1 3 All these techniques induce a donor site defect and extend the operating time. A simple and quick reconstructive procedure for the treatment of this *Corresponding author. Tel.: þ ; fax: þ address: jan-dirk.raguse@charite.de defect is the use of the localised buccal fat pad flap (BFPF) which was described for closure of difficult oro-antral and oro-nasal communications by Egyedi in The big disadvantage with this pedicled flap is that it is not epithelised. In the closure of oroantral and/or oronasal communications the resurfacing of the grafted fat with fibrous scar tissue might be an advantage in providing an adequate solidity in the plate. This fibrous effect is unfavourable when the BFPF is used in the reconstruction of buccal defects as it might functionally impair speech, mastication and deglutition. 5 Therefore Egyedi covered the flap with split-thickness skin graft with the disadvantage of producing a donor site defect. Tideman has shown S /$ - see front matter Q 2004 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserved. doi: /j.bjps

2 Buccal fad pad lined with Dermagraft for defects of the buccal plane 765 Table 1 Growth factors and cytokines in Dermagraft Function Material and methods Dermagraft Growth factor PDGF-A IGF KGF HBEGF TGF-a TGF-b1 TGF-b2 VEGF SPARC Matrix proteins Collagen Type I, III Fibronectin Tenascin Glycosaminglycans Veriscan Decorin Betaglycan Syndecan Mitogen for fibroblasts, granulation tissue, chemotactic Mitogen for fibroblasts Mitogen for keratinocytes Mitogen for keratinocytes, fibroblasts Mitogen for keratinocytes, fibroblasts Stimulates matrix deposition Stimulates matrix deposition, anti-scarring Angiogenesis anti- and pro-angiogenenic Major structural protein for dermis Cell adhesion, spreading, migration, mitogenesis Induced in wound healing, control of cell adhesion Structural, binds hyaloronic acid and collagen Binds growth factors, influences collagen structure TGF-b Type III receptor Binds growth factors, enhances activity The applied human dermal replacement consists of human juvenile fibroblasts seeded onto a threedimensional scaffold. In this setting the tissue is grown in closed bioreactors. After tissue formation the dermal replacement is cryoconserved at minus 80 8C and can than be shipped worldwide. When used the tissue is removed from the freezer and ready for implantation within minutes. The product is thawed at 37 8C and the cryopreserving fluid is rinsed with saline three times. Then the product should be implanted within the next 30 min. The product has several benefits. After 2 days the living implanted cells gain their full metabolic activity. This results in the secretion of a full complement of growth factors and cytokines (Table 1). As these growth factors derive from living cells they are delivered in a physiological concentration over a longer period of time. The growth factors include vascular endothelial growth factor (VEGF), which is essential for the formation of granulation tissue. Beside the several growth factors matrix proteins are secreted which provide an excellent matrix for epithelialation. that the BFPF might epithelialises within 2 3 weeks without any resurfacing but Stajcic reported that the extent of granulation tissue formation of the uncovered BFPF is unpredictable. 6 Fujimura describes a combination of the BFPF in combination with lyophilised porcine dermis to overcome the problem of epithelisation, granulation tissue formation, prevention of infection and alleviate postoperative pain. Scar retraction and limitation of the oral opening remains the main problem with the BFPF for reconstruction of buccal defects and hampers the wide use of this otherwise simple technique. The commercial availability of a bioengineered dermal replacement (Dermagraft) consisting of living metabolic active fibroblasts combined with the BFPF might regenerate the mucosal lining avoiding major side affects. Patients Reconstruction of a buccal defect after resection of a SCCHN was performed at the Charité Department of Oral and Maxillofacial Surgery of the Charité University Clinic Berlin from October 1999 through June Four patients were female and two patients male. All patients had a newly diagnosed untreated histological proven SCCHN. All patients had severe co-morbidities like advanced arteriosclerosis or diabetes which made a short operating time desirable. The extent of the tumour was from 7to12cm 2. Further staging examinations included chest X-ray, ultrasound of neck and abdomen. The TNM stage and extend of the tumour is presented in Table 2. The patients were treated according to their preoperative lymph node staging by Table 2 Patients characteristics Pat-number Sex Age Site of tumour Size of tumour (mm) Stage (TNM) 1 Female 45 Buccale T 2 N 0 M x 2 Male 53 Buccale T 2 N 0 M x 3 Male 46 Buccale T 2 N 0 M x 4 Female 51 Buccale T 3 N 0 M x 5 Female 70 Buccale T 2 N 0 M x 6 Female 85 Buccale T 3 N 0 M x

3 766 J.D. Raguse, H.J. Gath suprahyoid neck dissection with intraoperative lymph node monitoring and frozen sections. Surgical technique After cleared resection margins the BFPF is mobilised by opening the buccal soft tissue laterally and cranially from the defect. If this is not possible the BFPF can easily mobilised by an incision in the superior vestibular sulcus at the level of the upper second molar backwards. After cutting the mucosa and the buccinator muscle the buccal fad pad can be released. The buccal fat pad is identified by the yellow colour with small vessels on its surface. It prolapsed easily with external pressure on the cheek. At this point the suction has to be used with special care to avoid injuring. With additional blunt sections the fad pad is mobilised and then secured with resorbable sutures in the defect. After the positioning of the fad pad Dermagraft is thawed as described earlier. A gauze is used to determine the size of the defect to be covered. As Dermagraft is secured in the bag with two tags the template can be placed on the plastic cover and then the form can be cut. The plastic cover can then be easily removed and the tissue can be taken by forceps and transferred to the fad pad. Cautery of bleeding vessels is essential to avoid a haematoma between the fad pad and the transplant. The transplant easily adapts to the fad pad and is secured by 4/0 resorbable sutures (Fig. 1). The patients received nutrition by nasogastral tube for at least 3 days followed by liquid nutrition for 5 days. The implant quickly incorporates and dehiscence was observed. The vicryl structure of the implant resorbs within 10 days so no further procedure is necessary. To protect the implanted cells only physiological saline water was allowed as a mouth wash. Figure 2 signs. Results In all patients the defect was closed with the described technique (Figs. 2 and 3). Beside the pure cover no change of texture at the reconstructed site was observed giving the impression the defect was not only reconstructed but regenerated. Limitations regarding speech mastication and deglutition were not observed even after a period of more than 2 years (Fig. 4). Discussion The same defect after two weeks with strong The BFPF was first described by Egyedi for the closure of oroantral and or/oronasal communications. Since then the easy mobilisation with barely any donor morbidity inspired surgeons to use this flap for closure of defects at the hard palate, the soft palate, the retromolar trigone, the anterior tonsillar pillar and the buccal side. Even combinations with of the BFPF with a pedicled Figure 1 The BFPF in the buccal defect of mm 2 in a 70-year-old female covered with Dermagraft. Figure 3 The full closed defect in the same patient after 2-month.

4 Buccal fad pad lined with Dermagraft for defects of the buccal plane 767 Figure 4 No impairment in mouth opening occurred. temporalis muscle myofascial flap are described. 7 The size of the defects to be closed varies significant. Egyedi recommended its use for defect up to 4 cm in diameter. Tideman reported a reconstuced defect of mm 2. 8 Even larger defects up to mm 3 can be covered when using the BFPF in combination with a lyophilised porcine dermis. More concerning is the prolonged time of epithelialisation with possible scar retraction in larger unprotected surfaces. Fujimura wanted a biological dressing for the BFPF to facilitate proper formation of granulation tissue and epithelialisation, and this lead us to combine the BFPF with Dermagraft. We demonstrated that it is possible to regenerate with the use of Dermagraft, defects at the anterior floor of the mouth with histological no sign of scar formation. 9 Even larger defects for instance of the tongue were regenerated by simply using Dermagraft as a biological active dressing. For these not expected healing pattern the secretion of different growth factors from the fibroblasts to the wound bed seem to play an important role. It is documented that Dermagraft secretes vascular endothelial growth factor (VEGF) up to 700 pg/106 cells per day. 10 VEGF is a key growth factor for angiogenic vessel formation and granulation tissue formation which provides a ideal bed for epithelial closure. In this process Keratinocyte Growth Factor (KGF) also found in Dermagraft might be beneficial. The Table 3 The different stages of wound healing and substances secreted by Dermagraft which influences this process

5 768 J.D. Raguse, H.J. Gath complex mechanism involved in wound healing is only understood in parts. Table 3 shows the different stages of wound healing and substances secreted by Dermagraft which influences this process. As the fibroblasts are seeded on the BFPF they might work as local bioreactors secreting a whole panel of growth factors in appropriate amounts supporting wound healing. The efficacy in the mouth may be because the moist and warm environment is beneficial for the living fibroblasts. The limitation of Dermagraft in oral defect closure is that no thickness of the tissue can be generated. In combining the BFPF with Dermagraft the BFPF serves as a filling tissue on which a surface regeneration can then be achieved. Until bioengineered tissue with more thickness or even consisting of different tissue components like dermis and muscle is available combination of common flap techniques with bioengineered products might lead to faster more convenient reconstruction procedures. References 1. Futrell JW, Johns ME, Edgerton MT, Cantrell RW, Fitz-Hugh GS. Platysma myocutaneous flap for intraoral reconstruction. Am J Surg 1978;136(4): Dean A, Alamillos F, Garcia-Lopez A, Sanchez J, Penalba M. The buccal fat pad flap in oral reconstruction. Head Neck 2000;23(5): Soutar DS, Scheker LR, Tanner NS, McGregor IA. The radial forearm flap: a versatile method for intra-oral reconstruction. Br J Plast Surg 1983;36(1): Egyedi P. Utilization of the buccal fat pad for closure of oroantral and/or oro-nasal communications. J Maxillofac Surg 1977;5(4): Fujimura N, Nagura H, Enomoto S. Grafting of the buccal fat pad into palatal defects. J Craniomaxillofac Surg 1990; 18(5): Stajcic Z. The buccal fat pad in the closure of oro-antral communications: a study of 56 cases. J Craniomaxillofac Surg 1992;20(5): Tideman H, Samman N, Cheung LK. Immediate reconstruction following maxillectomy: a new method. Int J Oral Maxillofac Surg 1993;22(4): Tideman H, Bosanquet A, Scott J. Use of the buccal fat pad as a pedicled graft. J Oral Maxillofac Surg 1986;44(6): Gath HJ, Hell B, Zarrinbal R, Bier J, Raguse JD. Regeneration of intraoral defects after tumor resection with a bioengineered human dermal replacement (Dermagraft). Plast Reconstr Surg 2002;109(3): discussion Pinney E, Liu K, Sheeman B, Mansbridge J. Human threedimensional fibroblast cultures express angiogenic activity. J Cell Physiol 2000;183(1):74 82.