Engineering Graded Tissue Interfaces - Structural Interfaces and Attachments in Biology - page 299

14.3.6 Gradients in Mechanical Properties
Mechanics-based differentiation may be critically interdependent with extracellular
matrix composition, and this may regulate cell behavior. Matrix stiffness affects
cytoskeletal signaling elements that regulate differentiation, cell spreading [ 74 ], cell
motility [ 75 ], and matrix assembly [ 76 ]. Specific ligands together with substrate
compliance regulate differentiation [ 77 ]. To better suit the functions at the interface,
the scaffold needs to be designed for varying mechanical properties which can be
achieved by changing the porosity across the scaffold, as porosity is more dominant in
determining the scaffold mechanical properties than pore size. It has been
hypothesized that this stepwise transition in stiffness is important for the proper
functioning of cartilage and distribution of forces. Sharma et al . [ 78 ] identified that a
mechanical gradient in substrate and ligand loading could direct tenogenic and osteo-
genic differentiation of stem cells, so these could be considered as potential design
variables for engineering a functional interface between tendon and bone. More
recently, biphasic but monolithic materials were fabricated by joint freeze-drying
and chemical cross-linking of collagen-based materials (mineralized or coupled with
hyaluronic acid), as well as by ionotropic gelation of alginate-based materials (with or
without hydroxyapatite ceramic particles), which achieved specific mechanical
properties (e.g., elasticity or compression strength) [ 79 ].
To engineer a functional muscle-tendon tissue, Ladd et al . [ 80 ] developed a
scaffold with regional variations in mechanical properties and strain profiles to
mimic native muscle-tendon junction (MTJ). Muscle tissue is highly compliant,
with reported moduli values ranging from 0.012 to 2.8 MPa [ 81 , 82 ]. Tendon tissue
is stiffer in terms of tensile loading with reported moduli of 500-1850 MPa
[ 83 - 86 ]. The junction serves as an interface to reduce stress-concentrations and
failure at this interface [ 87 ]. The scaffold possessed both a compliant/high strain
region, a stiff/low strain region, and an intermediate region fabricated by a
co-electrospinning method. PLLA fibers with high stiffness, strength, and low
ductility were used to engineer tendon, and PCL fibers that were less stiff and
more ductile were used as the muscle scaffolding system. Co-electrospinning
resulted in a scaffold that had high stiffness and low compliance on one end yet
low stiffness and high compliance on the other. The middle region possessed an
intermediate stiffness and strain, which are analogous to the tendon, muscle, and
junction. The dual scaffolding system promoted the attachment of myoblasts and
allowed them to differentiate into myotubes and also supported fibroblasts.
The application of medical imaging systems together with computer-aided design
(CAD) has largely dealt with the problem of matching anatomical requirements of the
tissue engineered scaffolds [ 88 ]. A bio-plotter system can control design factors,
including pore size and shape, porosity, strand orientation, strand distance, and inter-
connectivity. In stereolithography, a gradient in size and volume fraction of the pores
can be introduced by adding a linear term to the equation used to describe the pore
architecture [ 89 ]. Park et al. [ 90 ] reported that PCL scaffolds fabricatedwith controlled
pore architecture using rapid prototyping methods have a higher mechanical strength
and promote better cell infiltration than scaffolds fabricated by salt leaching methods.