Use of Biologic Agents for Lip and Cheek Reconstruction

Abstract

The unique requirements of reconstructing cheek defects, often with its proximity to the mobile elements of the face including the lip and the eyelid, have been met very handily with the directed and thoughtful use of biologic wound healing agents. One of the key advantages of these agents is their ability to provide coverage for the mobile elements of the cheek and the lip in patients with multiple co-morbidities. These agents are successfully used where the standard cheek closure techniques including cervicofacial advancement flap are contraindicated due to its anesthetic requirement. Additionally, lip reconstruction involves examining the lip's three anatomic layers: mucosa, muscle, and skin. The defects must be planned for reconstruction based on the involvement of these layers. This paper serves to introduce the use of biologic wound healing agents depending on the involvement of these layers. The authors provide specific illustrations of these agents based on defect location, tissue involvement, and severity of the defect to help with procedural planning to reconstruct a very aesthetically involved part of the face.

Cutaneous malignancies are very common with an annual incidence rate exceeding 7.3% in the United States alone. ¹ Even though most skin cancers exhibit limited metastatic potential and have a favorable prognosis, all histological subtypes can be locally destructive necessitating extensive surgical resection. ^{2 3} Plastic surgeons are frequently tasked with reconstructing postablative defects of the cheeks and lips given the aesthetically sensitive nature of these facial structures. Furthermore, these regions play a pivotal role in one's ability to perform multiple vital functions including interpersonal communication and the consumption of solids and liquids. ^{4 5} Locoregional tissue transfer and skin grafting techniques have long been considered the gold standard for lip and cheek reconstruction; however, the advent of biologic wound agents have allowed reconstructive surgeons to challenge this paradigm. Since first being used for burn reconstruction, biologic wound agents have been employed to reconstruct defects of the lower extremity, abdominal wall, and face. ^{6 7} Herein, we discuss the role of said technologies in reconstructing postablative defects of the lips and cheeks in patients following surgical resection of cutaneous malignancies.

Preoperative Evaluation

As with all forms of reconstructive surgery, meticulous preoperative planning is vital to optimize aesthetic and functional outcomes. Most importantly, a patient's surgical candidacy is a major determinant of the reconstructive options that are available to repair the defect at hand. The majority of patients undergoing reconstructive surgery following Mohs micrographic surgery typically have their procedure performed under sedation with long-lasting local anesthetic, as such the concern for life-threatening complications occurring during surgery is low. ^{8 9 10} The reconstructive surgeon should also elucidate whether or not the patient is on antiplatelet and anticoagulant medications. Generally, these medications do not need to be discontinued when reconstructing a single, small defect; however, the senior author often requires that patients discontinue both medications when reconstructing a single, large defect or multiple defects in one surgery to minimize intraoperative complications related to excessive bleeding. ⁹ Lastly, the surgeon must determine whether or not the patient has a history of prior surgery or radiotherapy as both can limit the viability of several reconstructive options. Patients who have a history of prior surgery of the face and neck may be less amenable to reconstruction using local and regional flaps due to previous scarring of the facial planes. ¹¹ Radiotherapy, on the other hand, can limit the viability of biologic wound agents and skin grafting techniques by inducing fibrotic changes to the wound bed. ^{12 13}

Lastly it is highly important to elucidate patient's desires and expectations regarding reconstruction and to provide information regarding potential reconstructive options. This is particularly important as failure to meet patient expectations often results in patients being dissatisfied with their reconstruction thereby increasing the likelihood that they will seek revisional surgery or file malpractice litigation against the surgeon. ^{14 15} While plastic surgeons are intrinsically driven to optimize cosmesis following reconstruction, several patient populations, particularly older patients, may favor single-stage reconstruction out of convenience rather than undergoing staged surgeries or dedicated wound therapy regimens that would provide improved aesthetic outcomes.

Lip Reconstruction

The lips are among the first facial structures people notice in interpersonal conversations with minor defects and distortions being easily noticeable to the average person. ^{16 17 18} In addition to their aesthetic importance, the lips manipulate oral competence which in turn allows the patient to eat, drink, and produce intelligible speech. ¹⁹ Additionally, the lips are also essential components of nonverbal communication as they play a pivotal role in the expression of emotion. When comparing the upper and lower lip anatomy, the upper lip has multiple aesthetically important subunits including the philtrum, white roll, and Cupid's bow ( Fig. 1 ).

Fig. 1.

Anatomy of the lips.

There are several challenges associated with using biologic wound agents for lip reconstruction. First, biologic wound agents are only able to reconstruct partial thickness defects of the mucosal and cutaneous lip as they require a wound bed to integrate with the patient's native tissue. Second, disruption of the wound bed–wound agent interface can occur secondary to voluntary and involuntary motions of the lip. Despite these limitations, the value of biologic wound agents for lip reconstruction cannot be understated.

Mucosal Defects

The approach to reconstructing lip defects isolated to the mucosa is largely determined by the size and location of the defect. Small defects of the lip mucosa should be reconstructed with direct closure assuming that it does not distort the surrounding lip. This is because direct closure is much less expensive when compared with biologic wound agent-assisted secondary intention wound healing and does not require multiple weeks of dedicated wound care. ²⁰ Large mucosal defects may be reconstructed with locoregional tissue transfer or by secondary intention wound healing. In regard to locoregional tissue transfer, smaller defects may be reconstructed by advancing the buccal mucosa using a multitude of flap designs to repair the defect. ^{21 22 23} In the instance that the defect is too large to be adequately reconstructed using advancement flaps, two-staged reconstruction using a cross-lip flap or tongue flap can reliably reconstruct these defects; however, the process is highly uncomfortable to the patient and produces significant color and texture mismatch between native and reconstructed vermillion. ^{24 25} Because of the limitations of locoregional tissue transfer, the senior author typically allows defects to heal secondarily with the assistance of biologic wound agents.

The senior author's method for this form of reconstruction has been previously described. ⁹ In short, the defect is packed with MicroMatrix (ACell Inc., Columbia, MD), an acellular dermal matrix in powdered form, prior to being secured by suturing a Cytal Wound Matrix sheet (ACell Inc.), an acellular dermal matrix, over the defect. Next, patients are instructed to place Surgilube (HR Pharmaceuticals Inc., York, PA), a water-soluble lubricating jelly, over the acellular dermal matrix up to five times a day over a period of 3 to 5 weeks. Using this methodology, the reconstructive surgeon can achieve excellent aesthetic outcomes when compared with local and regional flaps with little-to-no distortion of the lip ( Fig. 2 ). ⁹ It should be noted that the lip will develop dark granulation tissue before it eventually becomes replaced with natural-appearing mucosa at a later date ( Fig. 3 ). Other acellular dermal matrix products have been employed to reconstruct vermillion-only defects with similar aesthetic outcomes. ^{26 27} Should subtle differences persist following primary reconstruction, autologous fat grafting or fillers may be used for further correction. ¹⁹

Fig. 2.

Secondary wound healing using MicroMatrix and Cytal Wound Matrix to reconstruct a mucosal defect in a 72-year-old male following resection of a squamous cell carcinoma of the lower lip. Photographs taken before Mohs micrographic surgery ( A ), resultant mucosal defect ( B ), biologic wound agent construct secured with plain gut sutures ( C ), 5-months postoperatively ( D ).

Fig. 3.

Secondary wound healing using MicroMatrix and Cytal Wound Matrix to reconstruct a mucosal defect in a 76-year-old male following resection of a squamous cell carcinoma of the lower lip. Photographs taken before Mohs micrographic surgery ( A ), after Mohs micrographic surgery (B), at 15 days postoperatively ( C ), and 2 months postoperatively ( D ). Note how the extensive granulation tissue observed at 15 days postoperatively becomes replaced by normal mucosa.

Cutaneous Defects

The role of biologic wound technologies for reconstructing cutaneous defects of the lip is limited. Dermoconductive wound agents, such as Integra Bilayer Wound Matrix (Integra LifeSciences, Princeton, NJ), may be used to optimize the wound bed for definitive reconstruction with a full-thickness skin graft at a later date. When compared with skin grafting alone, use of biologic wound agents reduces the risk of scar contracture thereby minimizing the risk of distorting surrounding structures such as the vermilion or, in the case of the upper lip, the nose. ²⁸ In the instance that a defect involves the white roll and vermillion, MicroMatrix and Cytal Wound Matrix can be applied as described in the previous section as an alternative to the Abbe flap ( Fig. 4 ).

Fig. 4.

Secondary wound healing using MicroMatrix and Cytal Wound Matrix to reconstruct a defect involving the mucosa and skin in a 72-year-old male following resection of a squamous cell carcinoma of the upper lip. Photographs taken before Mohs micrographic surgery ( A ), resultant defect ( B ), 1 week ( C ), and 1 month ( D ) postoperatively.

Cheek Reconstruction

Successful cheek reconstruction is largely determined by the surgeon's ability to reconstruct the defect without causing retraction of the eyelids, lips, and nose. ^{29 30} The eyelid, in particular, is more susceptible to extrinsic forces, as such the reconstructive plan should account for this accordingly. The cheek is broken down into three aesthetic zones with each region having their own aesthetic and functional considerations ( Fig. 5 ). ³¹ Independent of the zone(s) that are affected, locoregional tissue transfer and skin grafting techniques are the primary reconstructive options used when correcting partial thickness defects. ^{2 32 33 34} Biologic wound agents are also a part of the reconstructive approach to partial thickness cheek defects; however, their use is limited to certain clinical scenarios ( Fig. 6 ).

Fig. 5.

Aesthetic subunits of the cheek. Zone one – suborbital zone; Zone two – preauricular zone; Zone three – buccomandibular zone.

Fig. 6.

The senior author's approach to cheek reconstruction with biologic wound agents.

The cervicofacial advancement flap is a staple of cheek soft tissue reconstruction. ³⁵ This procedure is contraindicated in patients who cannot discontinue anticoagulant and antiplatelet medications as failure to do so predisposes the patient to intraoperative complications. Patients who lack soft tissue laxity, such as patients who have previously undergone rhytidectomy, or cannot discontinue their anticoagulant and antiplatelet therapy are best served having their defect reconstructed using a biologic wound agent with or without skin grafting at a later date ( Figs. 7 and 8 ). Lastly, biologic wound agents may be used as a temporizing measure in patients whose surgical specimens are pending analysis by pathology though this is rarely done in the long-term setting given the prohibitive cost of said agents. ³⁶

Fig. 7.

Two-staged cheek reconstruction using Integra bilaminar wound matrix in a 77-year-old female following resection of a squamous cell carcinoma of the right cheek. Photographs taken before Mohs micrographic surgery ( A and B ), resultant defect involving zones 1, 2, and 3 demonstrating ingrowth of the acellular dermal matrix ( C ), placement of a split-thickness skin graft over the neodermis ( D ), 12 months ( E ) and 3 years ( F ) postoperatively.

Fig. 8.

Two-staged cheek reconstruction using Integra bilaminar wound matrix in a 55-year-old male following resection of a squamous cell carcinoma of the right cheek. Photographs taken before Mohs micrographic surgery ( A ), resultant defect involving zone 1 with placement of the acellular dermal matrix ( B ), 1 week after the application of Integra showing proper ingrowth and take of the scaffold ( C ), 6 weeks following showing complete take of a split-thickness skin graft ( D ), postoperative result at 4 months ( E ), 7 months ( F ), and 15 months ( G ) following resection of his malignancy.

The senior author most frequently employs Integra products when reconstructing head and neck defects. A more thorough discussion about the technical placement of Integra is presented in this issue of Seminars in Plastic Surgery (Technical Refinements with the Use of Biologic Wound Agents); however, we will provide a brief overview in this section. After thorough preparation of the wound bed and removal of nonviable tissue, the acellular dermal matrix is designed to fit the defect and is subsequently placed with the thick inner matrix facing the wound bed. After being secured with suture, a bolster with antibiotic ointment is placed on the suture and remains there approximately 1 week following the procedure. Should the defect be too large to heal by secondary intention wound healing, a split-thickness skin graft can be harvested and placed over the neodermis at approximately 6 weeks following surgery ( Fig. 9 ).

Fig. 9.

Two-staged cheek reconstruction using Integra bilaminar wound matrix in a 76-year-old male following resection of a squamous cell carcinoma of the right cheek. Photographs taken before Mohs micrographic surgery ( A ), resultant defect involving zone 2 with placement of the acellular dermal matrix ( B ), 6 weeks after the application of Integra showing proper ingrowth and take of the scaffold ( C ), postoperative results following reconstruction with split-thickness skin grafting at 4 months ( D ), 14 months ( E ), and 25 months ( F ) following resection of his malignancy.

Laser Therapy

Laser therapy has a unique role in Mohs reconstruction in patients who heal by secondary intention or undergo definitive reconstruction of cutaneous defects with split-thickness or full-thickness skin grafts. The primary indications for using lasers are to resurface skin grafts to improve contour, correct postoperative erythema, and to treat postoperative scars that are not responsive to noninvasive therapies. ^{14 37 38 39} Ablative lasers, such as fractional carbon dioxide (CO ₂ ) laser systems, function by directly transferring energy into tissues whereas nonablative lasers, such as pulsed dye laser systems, function by disrupting the vasculature supplying the overlying tissue. ^{40 41} Both ablative and nonablative lasers have been shown to be highly effective at treating postoperative scarring and erythema; however, ablative lasers are generally more effective at treating hypertrophic scarring should it occur. ³⁷ CO ₂ lasers are the laser of choice in patients who seek resurfacing of their full-thickness skin graft to improve its contour following surgery. ^{38 42} When compared with nonintervention controls, resurfacing of full-thickness skin grafts with CO ₂ lasers greatly improves graft adaptation to the surrounding skin, skin roughness, pigmentation irregularities, and overall patient satisfaction. ⁴²

Conclusion

Reconstruction of lip and cheek defects following surgical resection of skin cancers poses a challenge to the reconstructive surgeon given the functional and aesthetic importance of both structures. While not frequently used, biologic wound agents serve an important role in lip and cheek reconstruction—particularly in patients who are not medically fit for reconstructive surgery. Laser therapy, when indicated, is an invaluable tool for optimizing aesthetic outcomes in patients who undergo skin grafting or heal by secondary intention following the use of biologic wound agents. Looking ahead, advances in biologics, along with further investigations regarding their use, will likely yield increasingly better results.

Erratum: The article has been corrected as per Erratum published on May 30, 2022. DOI of the Erratum is 10.1055/s-0042-1749142.