Biomedical Engineering Reference
In-Depth Information
topography [53]. Dalby et al . have shown that the application of nanoporous topography
could promote human MSC osteogenic differentiation in vitro in a medium without
osteogenic supplements [52, 54], and showed the inductive effects of nanoporous topog-
raphy comparable with osteoinductive chemicals such as glycerophosphate-beta, ascorbic
acid, and dexamethasone. According to reports, fiber orientation in nanofibrous scaffolds
affects cell differentiation. Yin et al . have investigated the behavior of human tendon stem/
progenitor cells cultivated on aligned, randomly oriented poly( l -lactide acid) (PLLA) nano-
fibers and found that while on the aligned nanofibers, the cells tended to differentiate into
tendon cell lineages. On the randomly aligned nanofibers, however, they differentiated
along bone cell lineages [55]. These findings have shown that cells recognize biomaterial
topography at the nanoscale level and respond appropriately [56].
Nanotissue Engineering for Musculoskeletal Tissue
There are several properties associated with nanosized scaffolds that make them more
appropriate compared to micro- or macrosized scaffolds for tissue engineering. Nanosized
scaffolds possess improved biomechanical property compared to their micro-/macrosized
counterparts. In a nanosized scaffold, the area to volume ratio is relatively high, thus an
efficient exchange of oxygen and nutrients between the inside of the scaffold and its outer
environment occurs. This can lead to a significant reduction of necrotic zones that often
occur in the deeper zones of micro- and macroscaled scaffolds. Since nanoscale scaffolds
are tailored to mimic the native ECM of a tissue, they possess relatively more bioactive
surfaces than microsized conventional scaffolds for cell attachment, proliferation, and
differentiation. The greater bioactivity of the nanotextured biomaterial surface is the result
of a higher absorption of proteins that stimulate cell adhesion [57, 58].
Nanotissue Engineering for Bone
Bone tissue is a nanocomposite structure mainly composed of collagen I nanofibers and HA
nanocrystals embedded in a ground substance. Small-size bone defects heal spontaneously,
however, large defects require intervention. Among the available therapeutic strategies
for  promoting regeneration of massive bone defects, the tissue engineering approach is
promising. The objective of tissue engineering is to elaborate a bone tissue construct using
osteogenic cells cultivated on appropriate biomaterials. In this regard, MSCs are the pref-
erable cellular candidate.
The current biomaterials potentially applicable for bone tissue engineering include bioc-
eramics, natural and synthetic polymers, and a composite of bioceramics and polymers. Each
exhibits its own advantages and disadvantages, thus none can be considered as the ideal
biomaterial. For example, bioceramics that include HA and tricalcium phosphate (TCP) are
frequently used biomaterials for bone engineering. However, HA is not practically degraded
and remains inside regenerated bone tissue. Although TCP possesses biodegradability, it is
brittle compared with HA [59, 60]. The most widely used natural polymers in bone tissue engi-
neering include collagen, alginate, and chitosan. Weak mechanical strength, immunogenicity,
and the possibility of pathogen transmission are the most prominent disadvantages of these
biomaterials [7, 61].
In the search for a better alternative, synthetic polymers have been widely investigated.
The common synthetic polymers for bone engineering include poly(glycolic acid) (PGA),
poly(lactic acid) (PLA), PLLA, poly( d , l -lactide-co-glycolic) (PLGA), poly(ε-caprolactone)
(PCL), poly(propylene fumarate) (PPF), poly(caprolacton fumarat) and poly(caprolacton
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