Biomedical Engineering Reference
In-Depth Information
were equilibrated under high-pressure CO
2
before being rapidly returned to atmospheric pressure,
causing thermodynamic instability that led to the polymer foaming and creating an interconnected
structure around the NaCl particles. The NaCl particles were leached from the polymer struc-
ture scaffold to create a macroporous scaffold. The particulate polymer and microspheres fused to
form a continuous homogeneous matrix with open pore structure. The different approaches used
to incorporate VEGF into the scaffold led to different patterns of distribution of the growth factor
in the scaffold and variations to the release kinetics. Directly incorporating VEGF led to it being
located adjacent to scaffold pores and its rapid release, whereas pre-encapsulating the growth fac-
tor in microspheres prior to incorporation into the scaffold led to it being embedded deeply in the
scaffold, which delayed its release [94]. The same approach was used to incorporate two different
angiogenic growth factors (VEGF and platelet-derived growth factor) into a scaffold, creating a
dual delivery system [95]. Here, one factor was mixed with the particulate polymer while the other
was pre-encapsulated into the microspheres, resulting in the two growth factors being released at
different rates.
Alginate microspheres containing fi broblasts and bioactive glass particles have also been used
as angiogenic growth factor delivery devices [22]. Cells encapsulated in alginate microspheres are
not exposed to the host's immune system and thus avoid rejection, but are able to receive oxygen and
nutrients and release growth factors into the local host tissue. A solution of alginate-containing cells
and bioactive glass particles was used to fabricate microspheres by coacervation in a solution of
CaCl
2
. The cells encapsulated in the microspheres were stimulated by the bioactive glass particles
to secrete VEGF, which was released from the microspheres.
Since the process of neovascularization requires a number of different growth factors, the use
of cells, provided with an appropriate stimulus such as bioactive glass, is likely to be advantageous
over polymers providing single or dual growth factor delivery as it offers the ability to deliver sev-
eral types of angiogenic growth factors at more physiologically relevant doses.
However, scaffold fabrication processes become limited when biological agents, such as growth
factors, plasmid DNA, and viral vectors, are incorporated into the scaffold-processing techniques,
which involve the use of high temperatures and solvents that would be detrimental to the biological
activity of these agents. Composite polymers containing bioactive particles have been suggested
to provide a solution to these problems. Third-generation biomaterials, such as bioactive glass,
stimulate cell protein and gene expression [96]. The use of these nonbiological biomaterials can
eliminate the need to incorporate biological factors into the scaffold fabrication process, avoiding
the aforementioned problems while also potentially increasing the range of polymers/solvents/
temperatures that can be used to fabricate scaffolds and also increase the shelf life of prefabricated
scaffolds. The use of bioactive glass particles in polymer scaffolds has recently been shown to
stimulate angiogenesis. Polymer mesh scaffolds coated with a low concentration of bioactive glass
and implanted subcutaneously
in vivo
were found to stimulate signifi cantly greater infi ltration of
blood vessels into the polymer mesh compared with uncoated control scaffolds [97]. The mesh,
consisting of woven poly(glycolic acid) fi bers, was coated with 45S5 bioactive glass particles by
immersing it into a stable slurry of glass particles in distilled water. After allowing the coated
meshes to dry at room temperature, they were made porous again by fl exing that left a thin coating
of particles on the surface of the polymer fi bers [97]. The angiogenic response observed has been
suggested to result from the ability of certain bioactive glasses to stimulate cells infi ltrating the
scaffold to secrete angiogenic growth factors, such as VEGF, which stimulates angiogenesis and
neovascularization [98,99].
20.8 SUMMARY
Biomaterials have been used for many centuries to assist therapeutic strategies associated with the
gastrointestinal tract. Their usage continues to evolve with new applications, such as cavity fi lling
materials combined with the use of key-hole surgery, nanotechnology-based drug delivery systems,
