Jz. Gao et al., Tissue-engineered fabrication of an osteochondral composite graft using rat bone marrow-derived mesenchymal stem cells, TISSUE ENG, 7(4), 2001, pp. 363-371
This study tested the tissue engineering hypothesis that construction of an
osteochondral composite graft could be accomplished using multipotent prog
enitor cells and phenotype-specific biomaterials. Rat bone marrow-derived m
esenchymal stem cells (MSCs) were culture-expanded and separately stimulate
d with transforming growth factor-beta1 (TGF-beta1) for chondrogenic differ
entiation or with an osteogenic supplement (OS). MSCs exposed to TGF-beta1
were loaded into a sponge composed of a hyaluronan derivative (HYAF(R)-11)
for the construction of the cartilage component of the composite graft, and
MSCs exposed to OS were loaded into a porous calcium phosphate ceramic com
ponent for bone formation. Cell-loaded HYAFF(R)-11 sponge and ceramic were
joined together with fibrin sealant, Tisseel(R), to form a composite osteoc
hondral graft, which was then implanted into a subcutaneous pocket in synge
neic rats. Specimens were harvested at 3 and 6 weeks after implantation, ex
amined with histology for morphologic features, and stained immunohistochem
ically for type I, II, and X collagen. The two-component composite graft re
mained as an integrated unit after in vivo implantation and histologic proc
essing. Fibrocartilage was observed in the sponge, and bone was detected in
the ceramic component. Observations with polarized light indicated continu
ity of collagen fibers between the ceramic and HYAFF(R)-11 components in th
e 6-week specimens. Type I collagen was identified in the neo-tissue in bot
h sponge and ceramic, and type II collagen in the fibrocartilage, especiall
y the pericellular matrix of cells in the sponge. These data suggest that t
he construction of a tissue-engineered composite osteochondral graft is pos
sible with MSCs and different biomaterials and bioactive factors that suppo
rt either chondrogenic or osteogenic differentiation.