Future Directions - Articular Cartilage Tissue Engineering - page 88

88 CHAPTER 5. FUTUREDIRECTIONS
stimulation. However, loading is applied naturally by the normal physiological environment, which
could be termed the ideal cartilage bioreactor.
The in vivo growth of cartilage tissue depends on many different factors that cannot be
modeled well in vitro . For example, many cytokines and bioactive molecules exist in living bodies
that cannot be easily included in a laboratory experiment, either because they are still unknown, or
more practically, their sheer numbers are unreasonable for controlled studies. Using serum in the
culture media is intended to replicate these conditions somewhat, but results can be dramatically
different when the growth environment is an active, living body which can endogenously produce
bioactive molecules in response to the implanted construct. Even in an isolated tissue such as cartilage,
chemical and mechanical signals can impact the development of the tissue whether it is an empty
defect or an implanted construct.
Researchers investigating in vivo cartilage engineering have focused on repairing defect sites
with transplanted cartilage/cells, synthetic materials, and cell-seeded cross-linkable scaffolds. The
first includes autologous and allogeneic cartilage/cell implantation, in which cells or minced tissue are
inserted into a defect site and then kept in place with a covering, such as a periosteal flap [ 718 ]. The
second approach is primarily a stop-gap measure that would provide a mechanically functional insert
but does not allow regeneration of the tissue [ 741 - 743 ]. The third repair technique includes several
different types of synthesized polymers that can transition from a fluid to a stiff gel using either light
or heat as an initiator [ 417 , 744 ]. The mentioned in vivo repair techniques all have advantages and
disadvantages although none have resulted in long-term, functional repair of articular cartilage that
is comparable to healthy tissue.
ACI has been modified in various ways in animal studies. Instead of a cell slurry, expanded
chondrocytes have been condensed into spheroids first and then implanted into SCID mice [ 745 ].
Attempts have also been made by embedding cells in an alginate-gelatin hydrogel with subsequent
implantation in sheep. Hyaline-like repair tissue formed in both cases although better histological
scores resulted when chondrocytes were included [ 746 ]. Attempts have also been made at replacing
the periosteum flap with other materials, such as collagen sheets with embedded cells [ 747 , 748 ], and
it has been shown that symptomatic hypertrophy, disturbed fusion, delamination, and graft failure
observed with periosteum use can be subsequently reduced [ 749 ].
A possible approach to in vivo articular cartilage replacement is to insert synthetic constructs,
which would fill a defect and provide mechanical support and a low-friction surface. These cell-
less constructs would be non-resorbable and could likely find a niche as a stop-gap measure for
patients wanting to delay full arthroscopy procedures [ 742 ]. While not technically considered tissue
engineering, synthetic replacements do represent an attractive option due to their ease of handling
and modification. Synthetic replacements can provide structural support for limited periods of time,
but eventually more drastic procedures will be necessary as the conditions in the joint continue
to degrade. A scaffold that would not necessarily bear weight initially but would instead offer
ease in implantation would be photopolymerizable hydrogels. These allow for minimally invasive
implantations of the cell/polymer constructs [ 744 ].