Engineering Graded Tissue Interfaces - Structural Interfaces and Attachments in Biology - page 305

A continuous gradient in porosity and mechanical properties also enables smooth
stress transfer at the interface. Thus, scaffolds with a continuous gradient in their
properties can be a promising candidate for interface tissue engineering.
14.5 Conclusions
From a surgical and commercial standpoint, an ideal graft for regeneration of a
tissue interface would be an off-the-shelf product. The option of creating a cell-free
implant capable of inducing orderly and durable tissue regeneration is still under
investigation. An ideal scaffold is expected to have innate ability to stimulate
organogenesis rather than serving as a structural template for three-dimensional
deposition of ECM. Engineering of functional interfaces with structural hierarchy,
bioactive signal patterning, and appropriate mechanical properties is emerging as a
major challenge for the current generation of tissue engineers.
Cells play the most important role in co-engineering of two tissues and their
interface. Even though co-culture of relevant cells is straightforward, the use of a
single progenitor cell source and differentiating them into cells of an appropriate
phenotype at the interface in response to biological cues will be a more efficient
method. Patterning of biological signals is nature's approach for tissue development.
During the development and wound healing process, growth factor patterns enable
the homing of progenitor cells that result in appropriate cell density; this is followed
by condensation and tissue-specific differentiation of cells. This homing and con-
densation process could be effectively activated during in vivo tissue repair by
patterning of biological signals on 3D scaffolds [ 107 ]. Bioactive growth factors
have a significant influence on maintaining cell phenotype at the interface. Use of
single or multiple signaling molecules, their relative amounts, spatial arrangements,
and the temporal sequence in which they are presented need to be carefully exam-
ined while engineering interfaces. The growth factor carriers need to be tailored for
proper encapsulation to retain the bioactivity and release kinetics. Hydrogels have
been widely explored as a matrix for engineering soft tissue-bone interfaces. They
are flexible for signal encapsulation, bio-functionalization, and are suitable for
engineering soft tissues. Multiphase scaffolds using hydrogels and stiff polymers
with a continuous interface are good candidates for interfacial tissue engineering.
Integration at the interface can be obtained by interdiffusion of the two polymers and
appropriate cross-linking methods to attain a smooth gradient in properties. Studies
have shown that gradients of pore size influence cell behavior by regulating cell
morphology, proliferation, ECM deposition, and vascularization. The porosity and
mechanical properties of the scaffolds must be tailored to improve the stress transfer
at the interfacial junction. Gradient distribution of osteoconductive materials like
hydroxyapatite, CaCO 3 , and TCP in a monolithic scaffold may be a promising
approach to enhance stiffness and osteoconduction. The cell types at the interface
respond to the different micromechanical environments experienced locally and
remodel their surroundings. Continuous gradients can overcome the limitations of