Biomedical Engineering Reference
In-Depth Information
the encapsulated cells and the surroundings [54]. The permeability, config-
uration, and chemistry of the membranes have been tailored successfully by
various investigators to create membranes with optimal properties. Two com-
monly investigated polymeric systems include hollow fiber membranes of
poly(acrylonitrile)-poly(vinyl chloride) and microcapsules of alginate [5, 54].
Other than treating the above-mentioned diseases, cell therapy has also
been investigated for treating tissue loss in the musculoskeletal system. For
example, Autologous Chondrocyte Transplantation (ACT), Carticel (Gen-
zyme Biosurgery), an FDA approved product, utilizes cells alone to regenerate
lost articular cartilage. Here, the cells from the patients are first isolated
from a biopsy and then expanded ex vivo prior to their re-implantation [56].
Such an approach involving ACT to repair musculoskeletal lesions (e.g. large
chondral defects of the knee) was first introduced in Sweden in 1987. Since
then various researchers have investigated the success of ACT, and found
that the average success rate of repairing various lesions (such as femoral
chondyle, osteochondritis dissecans, etc.) using this technique is approxi-
mately 85% [57-59].
Bioscaffolds and Cells
When the defect sites are large and the cell migration from the residual sur-
rounding tissues is minimal or impeded, an implantation of both cells and
a functional scaffold is necessary for repair. In this approach, the scaffold pro-
vides the initial structural support to the encapsulated cells, and guides their
proliferation and differentiation into the desired tissue or organ. A cell pop-
ulation which has the ability to proliferate and produce the required matrix
is placed onto the defect site in combination with a biomaterial as shown
in Fig. 1. A number of cell sources exist for this purpose, and these include
fully differentiated cells isolated from tissue (e.g. chondrocytes for cartilage
repair), adult stem cells (e.g. bone marrow-derived mesenchymal stem cells,
MSCs) which are multipotent, or embryonic stem cells (ES) which are pluripo-
tent. The polymer scaffold acts as an artificial extra-cellular matrix (ECM) and
provides a favorable niche or microenvironment for the cells to grow towards
the desired lineage. Additionally, it also serves as a carrier for the transport of
cells into the defect site and also confines the cells to the defect site. Cells can
be either seeded onto a solid fibrous or porous scaffold or encapsulated within
a gelatinous scaffold. In both cases, the cells are suspended or attached to the
scaffold, and then they proliferate, migrate, and secrete ECM.
The chemistry as well as the biomechanical properties of the scaffold plays
a key role in the differentiation of stem cells to the particular lineage such
as cartilage, bone, or even muscle. Differentiation of adult and embryonic
stem cells is generally controlled by various cues from the microenvironment,
which will be discussed in more detail later. In short, designing a proper scaf-
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