Strategy for a Biomimetic Paradigm in Dental and Craniofacial Tissue Engineering - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 127

middle line where it meets the cartilage of the opposite side [51]. Thus,
beside its articulation with the vertebral column, it seems obvious that
the chondrocranium is directly and indirectly attached to the maxillary
and mandibular facial skeleton, respectively. Therefore, its growth could
morphologically set up the structural foundation of many aspects of the
craniofacial architecture [52].
Formation of the primary and secondary palates also takes place dur-
ing this stage. The primary palate joins the secondary (lateral) palatine
process, after their elevation. Then, the anterior part undergoes ossifi ca-
tion, which extends from pre-maxillary, maxillary and palatine centers,
to form the hard palate, whereas muscles develop posteriorly to form the
soft palate. These developmental processes are strictly controlled by a
complex genetic cascade that involves a number of critical developmental
genes [53].
The third stage of craniofacial development seems to coincide with
the beginning of human fetal life at the beginning of the 9th week. It is
characterized by formation of osseous and muscular tissues. The skeleton
of human skull consists of two parts; the viscerocranium, which forms
the facial bones, and the neurocranium that lodges the brain and com-
promises membranous neurocranium that forms the vault of the skull
and the cartilaginous neurocranium that forms the cranial base. The latter
serves as a growth plate that undergoes endochondral bone ossifi cation;
in an orderly postro-anterior pattern [54]. It is only after skeletal muscle
formation that secondary cartilage appears in the developing mandible.
Interestingly, in relation to the condylar head of the ramus, the defi ni-
tive tempromandibular joint (TMJ) replaces the primitive jaw joint that
was initially developed between the incus and malleus [55]. Also, after
formation of the basal parts of the maxilla and mandible, their alveolar
processes begin their development in relation to the developing tooth
germs.
Regarding tooth development, it is yet another highly coordinated and
complex process. It relies upon cell-cell interactions that result in tooth ini-
tiation and morphogenesis, both of which are regulated by sequential and
reciprocal interactions between the epithelium and the underlying neu-
ral crest derived mesenchyme [56]. These signaling pathways include the
TGFß, BMP, Wnt, FGF, Hedgehog and Eda (Ectodysplasin, a TNF signal)
which are used reiteratively during advancing tooth development [57].
It is noteworthy that the primary transient inductive role of epithelium
was shown in mice recombination studies which confi rmed that prior to
the bud stage of development the potential to induce tooth morphogen-
esis resides in the epithelium. Only epithelium of the fi rst branchial arch
could instruct tooth formation when cultured with neural crest derived
cells from second arch mesenchyme or with premigratory trunk neural
crest [58]. After the bud stage, this instructive capacity for tooth formation