Tissue Engineering: Focus on the Musculoskeletal System - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 207

and lungs, or intravenously, which requires transport through the blood
system to the target site. Intravenous injection has the obvious limitations
of being cleared by the liver and distributed throughout non-target tissues,
but inhalation has been used to deliver siRNA to the lungs for the treat-
ment of respiratory syncytial virus (RSV) [62]. This study used a siRNA
called ALN-RSV01, which acts against the mRNA of N-protein of RSV to
down-regulate its expression. This was a safety and tolerability study, but
testing has now entered phase II clinical trials. Another example of siRNA
delivery is the intratumoral injection of siRNA condensed by using a PEI
carrier [63]. Injection of siRNA complexes into tumors within the cranium
successfully decreased the expression of pleiotrophin, a known promoter of
U87 glioblastoma cell proliferation. While this is a tumor model, this tech-
nique can be easily adapted to treat other diseases such as osteoarthritis, by
down-regulating tumor necrosis factor-α in mice suffering from collagen-
induced arthritis [64]. Although applying siRNA delivery for tissue engi-
neering applications is a relatively young field, it holds great promise for the
future and we expect to see rapidly growing research efforts in this area in
the near future.
Technology for Manufacturing Tissue Engineering Scaffolds
Tissue-engineering scaffolds aim to induce tissue regenerations by engineer-
ing the behaviors of individual cells. To reach this goal, a properly designed
scaffold architecture should be developed to trigger desirable cellular fates
for biological functions of specified organs [65]. This requires not only con-
trolling the biochemical and physical properties of scaffold materials, as
previously mentioned, but also developing microstructures within the scaf-
folds. These microstructures should have dimensions comparable to the size
of cells (1 to 100 micrometers); they facilitate tissue regeneration by physi-
cally directing cell morphology, positioning, and alignment that resemble
those of tissues in vivo. The aforementioned honeycomb microchannels,
which direct the polarization and self-alignment of seeded cardiomyocytes,
are a good example. Likewise, microchannels of poly(lactide-co-glycolide)
(PLG) were used to guide the unidirectional extension and growth of neu-
rons in three-dimensional space [66].
In addition to guiding cell morphology, microstructures also take impor-
tant roles in sustaining cell proliferation. For example, interconnected micro-
porosity is commonly used to facilitate the diffusion of nutrients, wastes,
and signaling molecules in a tissue-engineering scaffold [67].
In fabricating a scaffolding microstructure, one needs first to decide which
type of scaffold precursor should be used; this precursor is usually a fluid
that can be solidified by certain mechanism.