Biomedical Engineering Reference
In-Depth Information
in capsule size should allow the use of immune-privileged sites for implantation such as
spleen capsules, omental pouch, or liver via the portal vein. Moreover, smaller capsules
would reduce the size of the capsule injection device, thereby reducing surgical trauma [20].
It has also been reported that a reduction in microcapsules size suppressed foreign body
response to the implanted microcapsules [21].
The reason for the impossibility in the production of droplets smaller than the needle
diameter with a narrow distribution in size using air as an ambient fluid is due to the
occurrence of fluctuations in the air flow under the flow rate necessary for obtaining such
droplets. The fluctuations in air flow result in a heterogeneous drag force which causes the
droplets to develop with a heterogeneous distribution in size [22]. For practical applications,
the distribution in microcapsule size is an important issue because of the response time
toward stimuli inducing secretions of therapeutic products from enclosed cells. Laminar flow
with a high flow rate of the ambient co-flowing fluid is essential for the production of smaller
droplets than the needle diameter to load a constant force to the cell-suspending aqueous
polymer solution for breakup into droplets. From the hydrodynamics point of view, such
laminar flow easily results from higher viscous fluid under the same flow rate. It means liquid
is more effective for obtaining laminar flow of ambient fluid than gas. In this chapter, cell-
enclosing microcapsules of about 100 μm in diameter were prepared using a needle with a
diameter of several hundred micrometers with a narrow size distribution by injecting a cell-
suspending solution into an ambient co-flowing liquid. The microcapsules produced are too
small to enclose pancreatic islets but are large enough to encapsulate single cells, 10-30 μm in
diameter. In addition, the novel process of gelation of the droplets in a water-immiscible
liquid via an enzymatic reaction, and application of the microcapsule production method for
developing cell-enclosing hydrogel fibers are also described based on our recent studies.
Droplets Production via Jetting Process
Using air as an ambient fluid, cell-enclosing microcapsules of about 100 μm in diameter
and a narrow distribution in size can be obtained by extruding a cell-suspending solution from
a nozzle with a width of several dozen micrometers [23,24]. Such small nozzles are produced
by microfabrication techniques. Today, microfabrication techniques are widely known but
practical usage of the techniques is less common. In addition, the risk of the nozzle clogging
or plugging increases with increasing viscosity of the extruding solution [25] and decreasing
nozzle diameter. Without complete dispersion, the suspended cells also become a risk
resulting in nozzle clogging and plugging. We attempted to develop the cell-enclosing
microcapsules of about 100 μm in diameter using medical syringe needles with a diameter of
several hundred micrometers. The small microcapsule preparation technique involves a
process of droplet breakup in a co-flowing water-immiscible liquid resulting in an emulsion
system. Well-known emulsification techniques include use of a magnetic stirrer and a
homogenizer [26,27]. These techniques are effective for obtaining droplets with a diameter of
about 100 μm. However, the droplets are heterogeneous in size. In contrast, the droplets
produced via the droplet breakup method in co-flowing ambient water-immiscible liquid in a
laminar flow fashion show a narrow distribution in size (Figure 2) [28]. The device for the
droplet breakup method is simple (Figure 1b) and almost the same structure as that which
