Biomedical Engineering Reference
In-Depth Information
interactions, via dip-coating or lyophilization, as it is the case with two clini-
cally used products for improving bone healing (Infuse; Medtronic Sofamor Danek,
Memphis, Tennessee, delivering BMP-2, and OP-1 Device; Stryker Biotech, Hop-
kinton, Massachusetts, delivering BMP-7) [
405
].
In those cases that is necessary to deliver the biomolecules encapsulated, either
for initial protection from enzymatic attack or for controlling their release into the
scaffold milieu the encapsulated material plays an important role as well. A recent
study showed important differences over spatial and temporal controlled delivery of
two recombinant human growth factors, bone morphogenetic protein 2 (rhBMP-2)
and insulin-like growth factor I (rhIGF-I), from PLGA vs silk fibroin microspheres
incorporated within an alginate gel, thus influencing the differentiation of human
mesenchymal stem cells (hMSCs) [
425
].
When bioinert surfaces of scaffolds are grafted with bioactive peptides, or other
pertinent biomolecules, cell recruitment from a pool of cells can be controlled.
The peptide REDV interacts with endothelial cells but not platelets, fibroblasts, or
smooth-muscle cells, whereas the peptide KRSR, which interacts with osteoblasts
but not fibroblasts [
426
]. This approach becomes important when different cells
have to cohabit a particular space to generate specific tissue (such as bone) and the
appropriate vasculature for the metabolic support of the newly formed tissue.
Combination of different biological factors are also being tried, including growth
factors, drugs and genes [
411
,
427
].
13.4.2
Cells
In a recent editorial, on the origins of the terms
Tissue Engineering
and '
Regener-
ative Medicine
'[
428
], reference is made to one of the pioneering attempts in tissue
engineering of a 'living skin equivalent' published in
Science
, in 1981 by Eugene
Bell, utilizing collagen (as scaffold) and fibroblasts, as the appropriate 'living' cells.
The choice of tissue-specific, fully differentiated cells, from the donor, to be used
as the tissue generators within predetermined favorable conditions, appropriate scaf-
folds and growth factors in vitro, or delivery of cell suspensions at the intended site
in vivo, is laden, however, with inherent limitations. Such cells, for example ker-
atinocytes and dermal fibroblasts, have very limited ability for self-regeneration,
and this accounts for the eventual failure of an initially promising engrafment of a
skin autograft [
429
].
What was the reason, however, that some dermal autografts exhibited vary-
ing degrees of successful engrafment? A plausible explanation has to do with the
presence or absence, within the cell suspension employed, of stem or progenitor
cells. The long-term success of a skin graft depends on the appropriate rate of
replenishment of stem cells in the graft.
The question therefore arises: what are the stem cells? and why are they impor-
tant? The stem cells are distinguished from all other cell types by two character-
istics. First, they are unspecialized cells capable of renewing themselves through
