Biomedical Engineering Reference
In-Depth Information
seeding the matrix with angiogenic growth factors such as vascular endothelial
growth factor (VEGF) and fibroblast growth factor two (FGF2) (Nillesen et al.,
2007), gene transfer and seeding endothelial cells into the matrix, but these
methods have produced limited success. Neovascularization occurs with a time
delay, so promoting vascular growth in a matrix that already is supporting other
cell growth does not play a central role in keeping the tissue engineered construct
alive; inosculation, the combination growth of existing vasculature, is much more
important to blood profusion to implants.
To solve the problem of matrix vascularization, Montano et al. (2010) have
shown that it is possible to create a prevascularized matrix in vitro that then can
be implanted and promote cell ingrowth. They accomplished this task by first
isolating human microvascular endothelial cells (HuMECs) and growing these
isolated cells on a variety of concentrations of fibrin, collagen and fibrin±
collagen hybrid hydrogels to optimize three-dimensional organotypic vascular
structure formation. Out of these scaffolds, the 10 and 11mg/mL fibrin-based
hydrogels were the only matrices that facilitated three-dimensional luminal
structure formation. Fibrin has been previously shown to promote vascular cell
growth, but previously fibrin matrices have only facilitated the growth of
vascular structures with the additional support of fibroblasts and keratinocytes.
The 10 and 11mg/mL fibrin matrices supported vascular structure formation in
vitro resembling embryonic development without the addition of other cells in
culture. This study showed that engineering pre-vascularized matrices in vitro is
within reach, but
the mechanical properties of
fibrin limit
its utility in
applications requiring structural support.
Another problem that should be considered when designing tissue engineer-
ing matrices is innervation. Innervation is particularly important when
engineering constructs for muscular applications, because motor and sensory
neurons are central to the proper functioning of that implant. In addition to being
a consideration when designing tissue constructs for tissue and organ implants,
tissue engineering matrices have been employed to solve the problem of axon
growth after spinal cord injury. In this scenario, tissue engineered matrices are
used to facilitate inosculation of the severed nerves. To the end of creating
innervated skin grafts, Schwann cells can be added to the tissue engineered
matrix to produce a two-fold increase in the number of sensory neurites
migrating into dermal implant (Blais et al., 2009). The development of inner-
vated muscle tissue is more complicated than just including Schwann cells in the
matrix. Electrical, chemotropic and mechanical stimulation must all be
optimized to manipulate innervation and create a functional matrix for muscular
applications. Because of the importance of electrical signals in nerve growth,
conducting materials such as polypyrrole, a conductive synthetic polymer, and
electrically conductive carbon nanotubes have been integrated into matrices
where nerve growth is a consideration. Some similar concepts have been used
when designing matrices to foster central nervous system healing. Along with
￿ ￿ ￿ ￿ ￿
Search WWH ::




Custom Search