Biomedical Engineering Reference
In-Depth Information
viruses without destroying many important aspects of the target tissue is a
balancing act, for sure, and the subject of numerous patents in this field. One of
the oldest and most effective methods for disinfection involves the use of
aldehydes such as glutaraldehyde. They are very effective at disinfection and
impart a chemical crosslink between the collagen fibers that is directly akin to
making leather. These crosslinks render the source tissue much more resistant to
degradation by enzymes but also render it inert with respect to host remodeling
or at least cell signaling attributes.
Dehydration steps are often part of a tissue process. These can be solvent-
based or done with vacuum pumps, and the goal is to provide a more stable
material for shelf storage. Much research has gone into the effects of various
freezing and freeze-drying techniques on the structure of the resulting matrix,
yet some ECM materials appear to be rather robust and affected very little by
freeze±thaw cycles. Drying a tissue means that for most applications it must be
rehydrated before use, typically in sterile saline in the operating room. Another,
less obvious benefit of drying is that a dry product offers many more standard
options for sterilization.
Decellularized tissues of animal origin are regulated by the US Food and
Drug Administration (FDA) and many other regulatory bodies as medical
devices. As such, they must be terminally sterilized to exacting standards with a
sterility assurance of 10
ÿ6
(i.e. less than 1 device in a million can have a single
living organism present). Terminal sterilization of collagen-based materials is
not simple because many modes adversely affect the materials. For example,
intense heat from steam autoclaves causes collagen shrinkage and
denaturization.
2
Gamma radiation is an effective sterilization method for many
materials but for collagen-based materials it leads to chain scission and
decreased tissue strength and increased degradation rates (Seto et al., 2009).
This may be desirable for some applications, but not for most of the strength-
bearing uses of ECM grafts. Although some biochemical degradation is seen,
ethylene oxide sterilization at suitably low temperatures appears to be quite
compatible with ECMs, and even some of the newer methods, such as gas
plasma sterilization, are showing some promise for sterilization with tissue
preservation (Markowicz et al., 2006).
Decellularized tissues from human origin are regulated in the US as banked
tissues and not subject to the same sterilization rules. Their processes often
involve chemical disinfections and aseptic handling without the use of terminal
sterilization. This means that a much more rigorous process for screening donors
must be employed to help assure graft safety.
2. Although probably not appropriate for collagen implants, collagen shrinkage from boiling water
was the basis for shrunken heads in the jungles of South America. Don't try this at home.
