Harnessing Cell–Biomaterial Interactions for Osteochondral Tissue Regeneration - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 87

factors [ 175 - 178 ]. Delivery of growth factor to the cartilage defect site in an
animal model might be limited because of rapid clearance from the joint tissues
[ 175 ]. Therefore, as an alternative means of delivery of exogenous growth factor,
it has been hypothesized that overexpression of growth factors by transplanted
chondrocytes or MSCs might enhance the repair of articular cartilage defects.
Rabbit articular chondrocytes transfected with plasmid vectors encoding human
IGF-1 complementary DNA by using nonviral and nonliposomal lipid formula-
tions (FuGENE 6) demonstrated in vitro IGF-1 secretion from cells in the alginate
construct [ 176 ]. In addition to the in vitro IGF secretion from transfected cells in
alginate over a prolonged period (36 days), in vivo transplantation of the con-
structs led to enhanced articular cartilage repair and subchondral bone formation
compared with what was seen in groups that were transfected with the lacZ
reporter gene. This lipid-based transfection was also used for combined gene
transfer for both human IGF-1 and human FGF-2 in vivo [ 177 ]. This study
demonstrated that combined overexpression of both growth factors from NIH 3T3
cells encapsulated in alginate could accelerate the repair of full-thickness osteo-
chondral cartilage defects, compared with the group receiving IGF alone and lacZ
implants. In addition to nonviral gene delivery, viral vectors, including adenovirus,
lentivirus, and retrovirus, could also be used as gene transfer agents [ 178 - 180 ]. In
a study using adenovirus-mediated TGF-b 1 gene transfer to human MSCs,
improved cartilage repair was observed 12 weeks after osteochondral implantation
in a rat model [ 178 ]. FGF-2 has also been produced successfully by adeno-asso-
ciated-virus-delivered transgene and improved in vivo cartilage tissue repair [ 179 ,
180 ]. Moreover, direct implantation of vector-laden, coagulated bone marrow
aspirates (i.e., gene plug) has also been developed [ 175 ]. Typical ex vivo gene
transfection techniques require a series of processes including expansion of cell
number, transfection of cells with target genes, fabrication of cell/scaffold con-
structs, and surgical implantation [ 175 ]. By use of this alternative ex vivo protocol,
implantation of bovine bone marrow aspirate transduced with adenoviral vector to
deliver TGF-b 1 resulted in improved cartilage repair in partial-thickness defects of
the medial condyle in mature sheep models.
7.4 Modulation of the Intrinsic Properties of Biomaterials
Other than the incorporation of biological moieties such as peptides and growth
factors into hydrogel systems, there have been various investigations to enhance
the level of cell-material interaction by altering surface properties of scaffolds,
by modulating mechanical stimulation, and by changing the architecture of bio-
material scaffolds. In addition to promotion of cell-material interactions by
addition of biologically active stimuli, modulation of the intrinsic properties of
biomaterial substrates can also influence the chondrogenic differentiation of cell
populations as well as the in vivo tissue responses.