Biomedical Engineering Reference
In-Depth Information
substantially modified and active cells was a key argument in defining tissue
engineered products as advanced therapy medicinal products, a new category
of health care products in european regulation (european Parliament, 2007).
The bare fact that these products contain altered human or animal derived
material brings new elements into the ethical reflection on clinical trials.
it is the incorporation of living cells in the BTePs that generates perhaps
their most distinctive feature: the complexity of the process and the product.
This complexity is not present as extensively in other medical interventions
such as the implantation of prostheses. There are three closely related aspects
to this complexity: (1) BTePs are inherently variable constructs because they
contain metabolically active cells in a dynamic extracellular environment.
consequently, BTePs cannot be constructed in uniform batches according
to well-defined standards to the same extent as medical devices or medicinal
products (european commission, 2002).
(2) When a BTeP is implanted, we create a threefold dynamic to achieve
regeneration; (a) the dynamic within the BTeP itself, (b) the dynamic in the
recipient's body which may influence the incorporation of the BTEP (Stocum,
1998) and (c) the interaction of the recipient's body with the BTeP (ahsan
and nerem, 2005; caplan, 2007). a mismatch between the dynamics in
BTEPs and the body can render the product at best inefficacious, at worst
unsafe. For instance, the ideal implantation time for the BTeP may be
dependent on its developmental stage. if it is too 'green', or by contrast too
far developed, it may not integrate with the surrounding tissue. Understanding
the interactions between product and recipient is therefore essential for the
successful development of BTePs. To assess these challenges and to respond
to them accurately, a profound understanding of the biological processes
of tissue formation and regeneration, both in healthy and diseased tissues,
is essential, as is the ability to control cell phenotype and tissue formation
(Hollander
et al
., 2006).
(3) once the process of regeneration is initiated, it is impossible to reverse
it completely. if it goes awry, at best the BTeP can be removed. if, however,
cells of the BTeP migrate to other parts of the body and generate unwanted
secondary effects elsewhere, or if biomolecules affect other cells than the
BTePs', mere reversion of the procedure may be pointless to solve the newly
generated problem.
16.3.4 Value and validity
Whenever a trial is considered there ought to be at least strong indications
that the BTEP will be efficacious and that its findings will contribute to a
better understanding of bone tissue engineering. otherwise there are no
arguments to introduce it (emanuel
et al
., 2000). To establish the therapeutic
value of the BTeP, existing methodologies can and must be applied. These
