Strategy for a Biomimetic Paradigm in Dental and Craniofacial Tissue Engineering - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 133

induce mobilization of endothelial progenitor cells from the bone mar-
row to peripheral blood and that these cells themselves can promote
both neovascularization and osteogenesis in damaged bone tissue [84].
Peripheral blood of fracture patients showed an increase in the number of
circulating CD133 cells 48 hrs after fracture indicating their

possible role in initiating the healing process. Circulating osteoprogenitor
cells have also been identifi ed in fracture calluses of mice. These cells may
home to sites of injury by virtue of the infl ammatory milieu containing
high levels of chemoattractants such as SDF-1 and BMPs. Activation of the
SDF-1/CXCR4 axis by hypoxia, angiogenic peptides, and infl ammatory
cytokines may play a signifi cant role. It has been speculated that owing to
the intimate relationship between vasculature and bone, these circulating
cells indeed fi nd their way to the injury site via blood vessels [85].
However, it is important to note that although it appears that circulat-
ing osteogenic cells are major contributors to bone formation, late stage
osteoblastic cells and osteocytes expressing collagen type I and osteocalcin
do not circulate. It appears that the primary role of these cells is not bone
forming but that the latter is an adaptive response to injury or abnormal
cytokine signaling [85]. Levels of circulating cells fall to normal within a
few days after fracture or BMP-2 implantation, meaning that their response
is transient provoked by the injury and the infl ammatory nature of that
site [86, 87]. The presence of these circulating osteogenic cells holds great
clinical promise. Strategies could be developed to enhance the migration
of these cells thereby promoting natural endogenous repair mechanisms.
By increasing their mobilization they could be easily isolated from periph-
eral blood and utilized for cell-based therapies.

+ and CD34 +

6.5 Extracellular Matrix Nano-Biomimetics for

Craniofacial Tissue Engineering

Within the paradigm of tissue regeneration, knowledge has lately unfolded
about a whole new world of dwarfs, or nanos , where the actual molecu-
lar events that orchestrate cellular behavior, function and fate take place.
In the frame of the progressively acquired knowledge, nanotechnology is
being applied for tissue regeneration by deliberately fi ne tuning molecu-
lar particles in a microenvironment where the cells, the regeneration key
players, would recognize and “feel” their native home to attach, migrate,
proliferate, differentiate and secrete tissue-specifi c matrix.
Although no less challenging from any other application, nanotech-
nology is of particular relevance in the regeneration of the craniofacial
complex. Craniofacial tissues harbor highly specialized and functional
structures residing within a small volume demanding minimally invasive
interventions for aesthetic considerations. As for the uniqueness of the