Strategy for a Biomimetic Paradigm in Dental and Craniofacial Tissue Engineering - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 141

of cells in the center of large, cell-loaded constructs. While issues of vas-
cularization are of utmost importance for critical-size defect regeneration
all over the body, some features are particularly important for craniofacial
defects [165].
Within the craniofacial bones, the vascular supply is more consistent
with that of the cancellous bone where the blood, in contrast to compact
bone, reaches its anatomical destinations more directly without signifi -
cant branching. It is to be noted that most of the mid-facial bones are
covered by mucosa over large areas of their surfaces. Thus, every part
of these bones retains its periosteal blood supply. The blood supply of
the mandible, however, is a mixture of that of the compact and cancel-
lous bones and is therefore more susceptible to compromise [166, 167].
Although the craniofacial region has this abundant blood supply, it is com-
monly compromised after treatment with radiotherapy following cancer
surgery [165].
Bone regeneration is principally a part of the fracture healing process.
The majority of fractures heal well under standard conservative or surgi-
cal therapy. However, extended bone defects following trauma or cancer
resection require more sophisticated treatment, as spontaneous bone heal-
ing is unexpected. In a similar way, bone regeneration at the central region
of large constructs usually fails due to the absence of adequate vascular-
ization [164]. Although blood vessel ingrowth is often noted in implanted
tissue constructs over time, the vascularization is too slow or too limited
to provide adequate nutrient and oxygen transport to the transplanted
cells [168].

6.7.2 Patterns of Construct Vascularization

Neovascularization of grafted tissues or constructs occurs either by
sprouting of microvessels from pre-existing vasculature, a process termed
angiogenesis [169], or by in situ capillary plexus formation from endo-
thelial precursor cells (EPCs), a process termed vasculogenesis [170]
(Figure 6.12). A third pattern, namely “inosculation” refers to the devel-
opment of direct connections between the already existing capillaries of
a tissue graft or construct and angiogenic recipient-site vasculature [171]
(Figure 6.12).

6.7.2.1 Angiogenesis

The predominant mechanism of microvascular formation is that of angio-
genesis through migration, proliferation, and cooption of the existing
endothelium [172]. Sprouting angiogenesis commences mainly with pro-
teolytic degradation of the basement membrane around endothelial cells
(ECs) of a pre-existing capillary or venule [173].