Biomedical Engineering Reference
In-Depth Information
Nanoparticle and Tissue Regeneration
The mineral phase of natural bone consists of a calcium phosphate material widely known
as hydroxyapatite (HA, Ca
10
(PO
4
)
6
OH
2
) [65]. A variety of inorganic compositions have been
commercialized for biomedical application, including bioactive calcium-phosphate-derived
materials (such as HA or tricalcium phosphate (TCP, Ca
3
(PO
4
)
2
)), bioactive bioglass-
ceramic, or bio-inert materials (e.g. alumina, zirconia ,or pyrolytic carbon). Coating of
metallic prosthesis with the aim of enhancement in abrasion resistance, blood compatibility,
therapeutic delivery systems, or bone-tissue integrations are the common application for
bioceramics [66]. In addition, bioactive bioceramics, alone or in combination with polymers,
can be utilized as bone regenerative materials. Nanocomposites of gelatin-HA [67],
collagen-HA [68], poly(lactide-glycolide)-HA [69], polyurethane-fluorohydroxyapatite
[70], polycaprolactone-bioglass® 45S5 [71], and carbon nanotubes-bioglass [72], are a few
examples of nanostructures in “regenerative medicine.” However, it is well established that
for defects larger than a critical size, cell-scaffold construct together are required to be
approved in clinical setting [73]. On the other hand, incorporation of osteogenic factors
(such as TGF-β2, bone morphogenic protein 2 (BMP2), or insulin-like growth factor (IGF))
into the scaffold structure may be considered as a promising therapy for regenerating bone
tissue in critical defects [74]. Some researchers have introduced the process of immobili-
zation of organic molecules on ceramic structures, for example, Pompe
et al
. described a
protocol for immobilization of growth factors on glass surfaces by means of a thin layer of
poly(octadecene-alt-maleic anhydride) [75].
Nanostructure Role in Clinical Tissue Regeneration
The intrinsic characteristic of nanostructures increases the chance of noncovalent interac-
tions with macromolecules due to the large contact area [76]. The same as the nanoparticles,
nanostructures such as nanofibers can be designed for delivery of bioactive molecules [77]. It
has been shown that the profile of protein adsorption to fibrous and nonfibrous structures
with the same chemistry is different [78]. In addition to the importance of the chemical inter-
actions, our findings also confirmed that the protein adsorption on a nanoweb physically
depends on the fiber alignment, size distribution, bead formation, and porosity (unpublished
data). Incorporation of nerve growth factor in ε-caprolactone and ethyl ethylene phosphate
[79], basic fibroblast growth factor in collagen coated with perlecan [80], and plasmid DNA
into poly(lactide) -poly(ethylene glycol) nano-fibers [81], are examples of biofunctional
tissue-engineered fibrous structures. Moreover, biologically inductive molecules such as
drugs, enzymes, or cytokines can be immobilized on the surface of nanofibers through
chemical (e.g. covalent bonding) reactions [82].
It has been suggested that nanofibrous structures possess the inherent potential for
differentiation of stem cells to specific cell lineages. These fibers can induce differentiation
signals due to their similarity to the nanofibrous structures of natural ECM [83].
Differentiation of MSCs cultured on silk fibers to ligament fibroblasts [84], PCL fibers
containing retinoic acid to neural cells [85], and also myogenesis [86] have been reported.
Conductive and inductive chemical or physical cues introduced by ECM are essential for
altering stem-cell phenotypes [87]. According to the aforementioned properties, electrospun
fibers have drawn much attention for commercialization of biomedical applications.
However, several drawbacks, such as protein denaturation (by using ultrahigh voltage
and severe solvents) or disproportional fiber diameters (related to the natural ECM), have
confined their usage [88, 89].
