Engineering Graded Tissue Interfaces - Structural Interfaces and Attachments in Biology - page 293

A continuously graded osteochondral construct that simultaneously regenerates
both cartilage and bone and promotes proper integration at the interface may be the
most promising way to firmly anchor a cartilage substitute to natural surrounding
tissues. Graded variations in extracellular matrix architecture and properties at the
tissue interface are nature's solution for connecting mechanically mismatched
tissues. Creating chemical and material gradients to mimic the heterogeneity of
cellular environments may be beneficial for engineering of interfaces.

14.3.3 Gradients in Growth Factor Concentrations

Cells in developing organs and tissues have the ability to detect and respond to
various types of signaling gradients by chemotaxis [ 35 ] for viability, migration,
proliferation and differentiation. A variety of growth factors, like the members of
transforming growth factor (TGF)- family and bone morphogenetic proteins

(BMPs) [ 36 , 37 ], insulin-like growth factors (e.g., IGF-1) [ 38 ], and fibroblast
growth factors (FGFs) [ 39 ], have shown promising roles in the regeneration of
cartilage, bone, and ligament. Independent deliveries and cocktails of these growth
factors have been delivered through scaffolds at various dose and release regimes in
an attempt to optimize the engineered tissue growth [ 40 - 42 ]. Oh et al. fabricated
fibril-based scaffolds with increasing gradients of three different growth factors as a
tool to investigate the cell response to chemotaxis (Fig. 14.1 ). Cylindrical scaffolds
with a surface area gradient were fabricated by centrifugation of PCL/F127 fibers.
Growth factors were immobilized onto heparin that was further linked to these
fibers via hydrogen bonding [ 43 ].
The presence or absence of these signaling molecules, their relative amounts,
spatial arrangements, and the temporal sequence in which they are presented need
to be carefully examined while engineering interfaces. Wang et al . [ 44 ] reported
the use of a single concentration gradient or reverse gradient of (BMP-2) and
(IGF-1), encapsulated in microspheres for osteochondral tissue engineering. They
found that calcium deposition and osteogenic markers, Collagen I, and bone-
sialoprotein (BSP) showed a corresponding increase of transcription level along
the (BMP-2) gradient. The presence of the hypertrophic chondrogenic marker Col
X also showed an increasing trend along the gradient. The presence of (IGF-1)
enhanced the effect of (BMP-2) in inducing osteogenesis and chondrogenesis.
However not much has been discussed in detail about the structure of the
interfaces. Engineering dual tissues and their interfaces require coordinated
activity of multiple growth factors. This can involve cooperative or opposing
activities between the signals and cross-talk and reciprocal interactions between
signaling pathways. The ability of graded signals to control patterning of cell
phenotype and tissue-specific extracellular matrix at the interface was also
investigated by Dormer et al . [ 45 ]. Phillips et al . [ 46 ] looked at zonal organization
of osteoblastic and fibroblastic cellular phenotypes for bone-soft tissue interface
by a one-step seeding of fibroblasts onto scaffolds containing a spatial distribution

b