Harnessing Cell–Biomaterial Interactions for Osteochondral Tissue Regeneration - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 89

7.4.2 Scaffold Architecture
Architectural Design for Cartilage Tissue Engineering
In addition to altering surface properties of biomaterials to improve cell-material
interactions, modulation of the structure and architecture of a scaffold can also
influence the cellular behaviors, since architectural changes, including pore size,
porosity, interconnectivity, and morphology of the substrate surface, can affect
subsequent cellular behaviors [ 189 - 192 ]. Architectural design is of importance in
fabrication of bone-tissue-engineered scaffolds to induce osteoblastic differentia-
tion [ 190 , 191 ], but the influence of structural parameters can also be observed in
altering chondrocyte behaviors and differentiation for cartilage tissue engineering.
One recent study demonstrated that morphological changes in four different
cell-graft systems, including hyaluronan web, collagen fleece, collagen gel, and
collagen sponge, affected chondrocyte distribution, morphology, and cell-scaffold
interactions [ 192 ]. Passive chondrocyte distribution throughout the inner region of
porous scaffolds might depend on porosity and structure, whereas changes in
cell morphology may be correlated to fiber size. In addition, adhesion might be
influenced by material composition through membrane receptors and adhesive
matrix molecules.
Nanofiber Mesh Scaffold
Another example of architectural changes for cartilage tissue engineering scaffolds
is a nanofiber mesh scaffold. Fiber meshes are commonly fabricated via an elec-
trospinning technique [ 193 , 194 ]. A potential advantage of electrospun nanofibrous
scaffolds is the similarity of the fiber diameter to that of native collagen fibrils,
which may provide an appropriate microenvironment for chondrogenic cell
responses [ 194 ]. However, there are also some limitations to nanofiber scaffolds,
such as insufficient control of pore size, inherent planar structure, and subsequent
limited cell infiltration into the inner region of scaffolds [ 194 ]. Nevertheless, many
researchers have shown that nanofiber mesh scaffolds can support chondrogenic
differentiation of MSCs seeded on the scaffold [ 195 - 198 ] as well as multilineage
differentiation, including osteogenesis and adipogenesis [ 199 - 201 ]. Composite
fibrous scaffolds can also be fabricated by the dispersion of nanoparticles (e.g.,
hydroxyapatite minerals) in polymeric solution for electrospinning [ 197 ]. Some in
vivo studies using nanofibrous scaffolds with MSCs revealed a promising method
to repair cartilage defects [ 202 , 203 ]. Six months after implantation, PCL nano-
fibrous scaffolds with both allogeneic chondrocytes and xenogeneic human MSCs
in a swine model exhibited higher articular tissue regeneration over acellular PCL
scaffold and the no-implant control [ 203 ]. Another in vivo study using periosteal
cells from skeletally mature New Zealand White rabbits was also reported [ 202 ].
Varying the diameter of fibers in fibrous scaffolds could provide different
architectures and morphologies of the substrate for cell interaction. Subsequent