The human face
becomes highly individualized during development. Orofacial tissues are arguably the most complex in the human body, accommodating multiple functions of vision, hearing, smell, taste, touch, chewing, speech, swallowing, and breathing. When the face is disfigured because of trauma, tumor resection, infectious diseases, or congenital anomalies, the physical and psychosocial effects are extremely detrimental. In 2000, the U.S. Surgeon General's Report on Oral Health stated that a serious facial and oral disfigurement “may undermine self-image and self-esteem, discourage normal social interaction, and lead to chronic stress and depression as well as to incurring great financial cost.”1
The prevalence of facial defects is summarized in .2–6
A myriad of congenital anomalies, such as cleft lip, cleft palate, hemifacial microsomia, and craniosynostosis, adversely affect the face. Facial trauma remains one of the most common injuries in war and peacetime and frequently presents as challenges for both esthetic and functional restorations. Chronic diseases result in dental, oral, and craniofacial defects. Postablative head and neck cancer patients frequently have significant functional disabilities and a poor esthetic outcome.
Examples of the Prevalence of Facial Soft Tissue Wounds in the United States
Facial defects are currently restored by the patient's own (autologous) tissue grafts, allogeneic tissue grafts, xenogenic tissue grafts, synthetic materials, or prosthesis.2
Autologous tissue grafts invariably necessitate donor site morbidity. For example, a patient missing a segment of the maxilla or mandible frequently experiences additional trauma, pain, and morbidity because of an autologous bone graft harvested from the donor site such as the ileum. Similarly, a patient's missing portion of the nose after facial trauma or skin cancer resection may be reconstructed by an autologous skin and soft tissue graft from the forehead, which creates additional scarring and disfigurement. Autologous grafts are often considered the clinical gold standard, because allografts, xenografts, and synthetic materials are associated with complications such as pathogen transmission, immune rejection, and suboptimal integration.7–12
However, a key drawback of autologous tissue grafting is donor site morbidity.13–15
In addition to the burden of reconstruction of facial defects, there is an increasing demand for facial augmentation or rejuvenation.13–15
Facial augmentation or rejuvenation is frequently achieved by repetitive injections of fillers of naturally derived tissue analogs or synthetic materials.16
For example, injectables are used to correct contour deformities and rhytids due to loss of soft tissue or aging. Current injectable fillers include collagen (xenografts and allograft), freeze-dried acellular dermal tissue, calcium hydroxyapatite spheres, and polymer beads of poly-l
-lactic acid (PLLA) and polymethylmethacrylate (PMMA). Such injectables must be host compatible and not cause immunogenic, inflammatory, or carcinogenic effects. Current fillers are frequently short lasting and require repetitive injections. The long-lasting polymer injectables such as PMMA or PLLA may be associated with clumping and foreign body reaction.17
Moreover, current injectables suffer from suboptimal integration with host tissue, premature degradation, and suboptimal remodeling with surrounding host tissue.
Dermal tissue can potentially be restored by an intricate combination of extracellular matrix fibers including collagen and elastin. Accordingly, extracellular matrix-based materials have been extensively used as acellular soft tissue fillers, including collagen-based homologs such as purified human collagen (CosmoDerm/CosmoPlast, Inamed Gauting, Germany), decellularized processed dermal allograft (Cymetra LifeCell Corporation, Branchburg, NJ), particulate fascia lata allograft (Fascian Fascia Biosystems, Los Angeles, CA), and xenogeneic materials such as bovine collagen (Zyderm/Zyplast [Allergan, Irvine, CA]). Bovine collagen has been widely used as injectable fillers.18
Most of these fillers can be injected readily as an in-office procedure. Given the xenogenic nature of bovine collagen, there are safety considerations including potential pathogen transmission and immunorejection. Even with normal skin tests, approximately 3% of patients develop foreign body reactions.18
Most natural fillers degrade within short periods of time after injection and necessitate repetitive injections.
Other naturally occurring human extracellular matrix substances, such as hyaluronic acid (HA), have also been extensively used in facial augmentation. HA in the skin is commonly depolarized with aging, leading to reduced ability to retain water.18
Thus, replenishing HA may improve skin appearance by rehydrating the subcutaneous tissue. Compared with collagen, HA lasts somewhat longer but still requires repeated injections.
Alloplastic materials may address some of the deficiencies associated with short actions of natural substances. Alloplastic materials include hydroxyapatite particles embedded in a highly viscous gel (Radiesse BioForm Medical, San Mateo, CA), PLLA microparticles (Sculptra Sanofi-aventis U.S., Bridgewater, NJ), and PMMA microspheres (Artecoll Pulmon Medical, Natal, South Africa). The role of tissue engineering in facial reconstruction or rejuvenation is to promote the use of biocompatible materials with or without biomolecules or cells that allow host tissue to remodel and achieve the desired characteristics. Optimally, the injectables should induce cellular ingrowth while undergoing degradation at a well-balanced rate. There has been little progress in the translation of tissue engineering approaches to the clinical setting of soft tissue reconstruction or augmentation, despite meritorious effort. The delivery of chemokines or cytokines that induce cell homing is likely to reach the clinical market before cell-based applications, because cell delivery may require ex vivo manipulations, training of current clinical practitioners on cell handling, and other undesirable features such as excessive cost and potential contamination.
The premise of this review is that collective advances in stem cell biology, cytokine biology, chemical engineering, biomaterials, and tissue engineering, especially in the past decade, have established the foundation for “biosurgery,” a new paradigm for facial reconstruction and augmentation. Biosurgery is based on the principles and practice of the delivery of bioactive cues, biopolymers, and/or cells that are tailored to restore facial defects, circumventing the typically short-term, nonregenerative practice of current facial filler procedures (). It is probable based on the existing experimental data that restoration of small facial defects or augmentation can be achieved by cell homing and without cell transplantation (). At this time, the restoration of large facial defects may still rely on cell delivery (). Biological regeneration of orofacial tissues overcomes most, if not all, of the drawbacks of autologous grafting or artificial materials. Undoubtedly, the end is near for current clinical practice of autologous, allogeneic, and xenogenic grafting. The projected advances in the coming years of facial reconstruction and/or augmentation will likely stem from integrated strategies of cell biology, cytokine biology, chemical engineering, biomaterials, and tissue engineering. A number of challenges need to be further addressed before broad applications of biosurgery in facial reconstruction and augmentation: Would it be possible to heal certain facial defects by cell homing and without cell transplantation in patients? How to induce cell homing? Are autologous cells always necessary? Can allogeneic cells or xenogenic cells be safely transplanted to heal facial defects? What are the scientific and business barriers associated with cell transplantation or cell homing approaches? Here, we will discuss some of these critical questions.
FIG. 1. Divergence of two biological approaches for facial reconstruction or augmentation. Cells, including stem/progenitor cells, may be injected in soluble matrices or seeded in preformed anatomically correct matrices for the healing or augmentation of dental, (more ...)