Biomedical Engineering Reference
In-Depth Information
The next size scale of interest is the 100 micron size scale, the size of a typical organ
microenvironment. Many organs have highly specific local geometries that may have to
be engineered in an ex vivo system. Hence, a particular microgeometry with parti-
cular mechanical properties may have to be produced. Clearly, challenging material
manufacturing issues arise. Further, the support matrix may have to be biodegradable
after transplantation and the degradation products nontoxic. Lactic and glycolic acid-
based polymers are promising materials in this regard. If little restructuring of implants
occurs following grafting, then the geometry of the support matrix over larger size scales
may be important.
The largest size scale is that of the bioreactor itself. Bioreactors in tissue engineering are
likely to be small with dimensions on the order of about 10 cm. The materials issues that
arise here are primarily those of biocompatibility. Although manufacturing technology
exists for tissue culture plastic, it is likely that additional issues will arise. The tissue culture
plastic that is commercially available is designed to promote adhesion, binding, and
spreading of continuous cell lines. Although such features may be desirable for continuous
cell lines, they may not be so for various primary cells.
6.4 SCALING UP
6.4.1 Fundamental Concept
As just discussed, tissue dynamics are comprised of intricate interplay between the
cellular fate processes of cell replication, differentiation, and apoptosis. They are properly
balanced under in vivo conditions. The dynamics of the in vivo conditions are a balance
of these biological dynamics and the constraining physicochemical processes. The basic
concept of design in tissue reconstruction is to engineer a proper balance between the
biological and physicochemical rates so normal tissue function can occur.
6.4.2 Key Design Challenges
Within this framework, many of the engineering issues associated with successful recon-
stitution of tissues can be examined. This section provides an engineering perspective of tis-
sue engineering and helps to define the productive and critical role that engineering needs
to play in the ex vivo reconstruction of human tissues.
Important design challenges in tissue engineering include the following:
Oxygenation—that is, providing adequate flux of oxygen at physiological concentrations
Provision and removal of cyto- and chemokines
Physiological perfusion rates and uniformity in distribution
Biomaterials, including functional, structural, toxicity, and manufacturing characteristics
Other issues associated with the clinical implementation of cellular therapies include the
design of disposable devices, optimization of medium composition, initial cell distribution,
meeting FDA requirements, and operation in a clinical setting. These cannot be discussed in
detail here, but some of these issues are addressed generally in the following section.
