Biomedical Engineering Reference
In-Depth Information
stage are the repair of skeletal and cardiac muscle fibers, the implant of fat cells for cosmetic
augmentation, the realization of vascular prosthesis and the selection of cells with a
neuroregenerative potential. Each of these applications may also take advantage of a possible
genetic modification of the patient's or of the donor's cells by the insertion of a modified, or
repaired or new gene.
Commercial distribution of such products could provide a relatively simple solution to
a common type of injuries, satisfying the needs of a large number of patients. When com-
mercial establishments began to provide these manipulated cells to surgeons within the
United States it became clear that such a class of products had not been explicitly consid-
ered by the FDA. Moreover the manipulation required was much more than that needed
for autologous bone marrow transplant, where the source tissue is harvested but hardly
“processed” at all.
Tissue Engineering of Bone
Particularly, in the repair of bone and cartilage, the tissue engineering approaches are
seeking to address the needs by the realization of viable substitutes that restore and main-
tain the function of the two types of tissues. With respect to standard drug therapy or
permanent implants, the tissue-engineered bone becomes integrated within the patient,
affording a potentially permanent and specific cure of the disease state. Any approach
involves one or more of the following key ingredients: harvested cells, recombinant signal-
ing molecules and three-dimensional matrices. Ideally the cells would attach to the scaf-
fold and proliferate and differentiate under the control of endogenous and exogenous
growth factors to ultimately organize into normal healthy bone or cartilage as the scaffold
matrix degrades.
Orthopedic surgeons had previously used autologous tissues (for ex. rib cartilage) without
regulatory board oversight. It was immediately obvious that different rules should apply to
tissue engineered products. For example, chondrocytes dissociation from healthy tissue and
their ex vivo expansion (to reach the proper number for reimplantation) would fall under the
somatic cell therapy product definition. Nonetheless, since chondrocytes were implanted in
defined lesion sites, contrary to systemic therapies, this treatment showed similarities with
some device products.
In defining rules, one must take into account the following: (i) the need of unconven-
tional culturing techniques. Cells do not organize into tissue or organs simply by cultur-
ing them in standard media, nor are they able to acquire the proper phenotype without
specific signaling/differentiating factors; (ii) the need of appropriate matrices and/or
biomaterials that provide the required structural scaffold properties at the lesion site and
that allow to be remodeled while the new tissue is being formed. Combination products,
derived from somatic cell and/or gene therapy products grown on different scaffolds may
evidence different biological properties depending on the scaffold itself; (iii) accessibility
of the lesion site by the specific surgical techniques needed to implant the cell/biomaterial
construct.
Since the chemical/physical properties of many synthetic matrices can be easily defined and
controlled and the surgical procedures needed for the new therapeutic applications can be
easily overviewed, the real new regulatory challenge is posed by the combination products and
the absence of rules for the manufacturing of their cellular components.
With respect to their mode of action, combination products can be divided into two main
categories: the metabolic support systems and the tissue repair/replacement products. Products
for bone and cartilage reconstructive therapies normally fall under the latter category. Cells are
either autologous or allogeneic multi or pluripotent cells—stem cells included—all of which
could also be genetically modified. The device part is generally identified as “natural biomaterials”
(collagen sponges, amniotic membranes, demineralized bone) or as “synthetic polymers”
(PLGA-derivatives, ceramics). They can be used either for temporary or permanent implants
in a wide range of applications.
Search WWH ::
Custom Search