The pharyngeal arches contribute extensively to formation of the face, nasal cavities, mouth, larynx, pharynx, and neck. A typical pharyngeal arch contains the following:

The derivatives of pharyngeal arch cartilages are mandible and plate as described above. The horseshoe-shaped primordium of the mandible is formed from ventral portions of the first arch. The cartilage disappears as the mandible develops around the cartilage of the first arch by intramembranous ossification (Fig. 8.2). Other derivatives of the first arch cartilage include the malleus and incus from the dorsal end of the first arch cartilage (Meckel cartilage; Fig. 8.2b) and surrounding ligaments. The remaining arches contribute to provide the supporting skeletal and cartilaginous structures, including the stapes in the middle ear, styloid process and part of hyoid bone from second arch, the remainder of hyoid bone from third arch, laryngeal cartilage from the fourth and sixth arch cartilages (Table 8.1).

The musculature derivatives of the first pharyngeal arch are the muscles of mastication and other muscles (Fig. 8.3; Table 8.1). The stapedius muscle, stylohyloid muscle, posterior belly of the digastric muscle, auricular muscles, and muscles of facial expression are derived from the second pharyngeal arch. The stylopharyngeus muscle is derived from the third pharyngeal arch; the cricothyroid, levetor veli palatine, and constrictor muscles of the pharynx are derived from the fourth pharyngeal arch; and the intrinsic muscles of the larynx come from the sixth pharyngeal arch.

A specific cranial nerve (CN) supplies each arch. The dermis and mucous membranes of the head and neck are related to the mesenchyme from the pharyngeal arches, so that these areas are supplied with special visceral afferent nerves. The trigeminal nerve (CN V) is the principal sensory nerve of the head and neck, and its caudal two branches (maxillary and mandibular) innervate the teeth and mucous membranes of the palate, mouth, and tongue (Fig. 8.4). The motor nerve of CN V innervates the muscles of mastication. The second, third, and caudal (fourth to sixth) arches are supplied by the facial nerve (CN VII), the glossopharyngeal nerve (CN IX), and the vagus nerve (CN X), respectively. The second to sixth pharyngeal arches innervate the mucous membranes of the tongue, pharynx, and larynx, respectively.

The spaces between the arches are clefts externally and pouches internally. Only the first pair of clefts persist as the external acoustic meatus, while the other clefts are obliterated. The expanding first pouch becomes the tympanic cavity and auditory or Eustachian tube. The remainder contributes to glandular tissue of the head and neck, including the palatine tonsillar crypts from the second pouch, the inferior parathyroid glands and thymus from the third pouch, and the superior parathyroid gland from the fourth pouch (Table 8.1). These tissues will migrate to their adult locations.

The tongue is a complex structure consisting of mucosa, muscles, and both general and special sensory innervation. The anterior two-thirds of tongue is formed from mesoderm of the first pharyngeal arch, whereas second to fourth arch mesoderm contributes to the posterior one-third of the tongue, which descends into the oropharynx by 4 years of age. These two tongue regions are separated by a V-shaped cleft called the terminal sulcus. Most of the tongue muscles are derived from myoblasts that migrate from the occipital myotomes, and are innervated by the hypoglossal nerve (CN XII).

Neural crest cells develop from neuroepithelial cells of the surface ectoderm along the edges of the neural plate. Bone morphogenetic protein (BMP) signaling is important in establishing this edge region and then regulates WNT1 expression, which drives neural crest cells to undergo an epithelial–mesenchymal transition and begin migration into the surrounding mesenchyme. Some cranial neural crest cells originate from rhombomeres, which consists of eight segments in the hindbrain, and migrate into specific pharyngeal arches. There are three main streams of neural crest cell migration from rhombomeres: R1 and R2 migrate to the first arch along with crest cells from the caudal midbrain region; R4 migrate to second arc; and R6 and R7 migrate to arches 4 to 6 (Fig. 8.5). These three distinct streams of neural crest cells provide axonal guidance cues for axons from ganglia forming in the head and neck region. Axons from the trigeminal ganglion enter the hindbrain at R2, while those from the geniculate and vestibuloacoustic ganglia enter at R4 and those from the petrosal and nodose ganglia enter at R6 and R7. No axons project to R3 and R5.

Neural crest cells populating the pharyngeal arches form the skeletal components characteristic of each arch and this process is controlled by pharyngeal pouch endoderm. As pouches form, they express a very characteristic pattern of genes (Fig. 8.6). BMP7 is expressed in the posterior endoderm, FGF8 is expressed in the anterior endoderm, PAX1 expression is restricted to the dorsal-most endoderm of each pouch, and SHH is expressed in the posterior endoderm of the second and third pouches. These expression patterns regulate differentiation and patterning of pharyngeal arch mesenchyme into specific structures. In addition, there are different expression patterns of transcription factors in each mesenchyme and they dictate the fate of development. As for the first arch, HOX genes are not expressed, but OTX2, a homeodomain-containing transcription factor that is also expressed in midbrain, is expressed. The second arch shows HOXA2 expression, while arches 3 to 6 express members of the third paralogous group of HOX genes, HOXA3, HOXB3, and HOXD3 (Fig. 8.6b) [5]. With the influence of such diversity of transcription factors, each arch receives signals emanated from pouch endoderm and forms arch-specific structures.

Surgical resection of tumors causes tissue defects following head and neck surgery. In oropharynx, wide defects of tissue cause various problems, such as disturbance of mastication, deglutition, and articulation, leading to a decreased quality of life. Thus, there is a need for a reconstructive or regenerative approach to restore lost tissues and prevent postoperative complications. In oropharynx, the reconstructive approach is a mainstay of treating surgical defects so far, and there are few references in the literature regarding the regenerative approach. The reconstructive approach using free flaps has advantages in immediate covering of tissue defects without xenobiotic rejection [8]. However, there exist problems such as the stretching ability in free flaps due to the difference of tissue characteristics. Thus, the regenerative approach should also be evolving in oropharynx.

Tissue engineering is an interdisciplinary field that applies the principles of engineering and the life sciences toward tissue regeneration [9]. Three elements have been adopted for tissue regeneration: regulatory factors, cells, and scaffolds. Tissue regeneration will be achieved when these three elements are appropriately provided. At present, there are some reports regarding each element.

Regulatory factors modulate cell behavior such as extracellular matrix production, cell proliferation and differentiation. Growth factors are peptide molecules produced by various cells and representative regulatory factors.

Transforming growth factor (TGF) β3 is one of the TGFβ isoforms that activate nuclear-translocating Smads and other intercellular proteins, leading to altered expression of target genes by first binding to TGFβ type II receptors before pairing together with two type I receptors [10]. Embryonic wounds are known to heal perfectly with no scars [11]. There are far fewer inflammatory cells in embryonic wounds, the inflammatory cells present are less differentiated, and the length of time that inflammatory cells are present is markedly reduced compared with adult wounds [12]. Embryonic wounds express very high levels of TGFβ3 but very low levels of TGFβ1 and TGFβ2 compared to adult wounds [11

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