Engineering Graded Tissue Interfaces - Structural Interfaces and Attachments in Biology - page 302

electrospinning protocols as shown in Fig. 14.3 . Gradients were found to enhance
cell infiltration and direct cell migration [ 103 ].
It should be emphasized that while multiphase scaffolds consist of different
phases, a key criterion for interface engineering is that these phases must be
interconnected and pre-integrated with each other, thereby supporting the formation
of distinct yet continuous multi-tissue regions. Furthermore, interactions between
cells relevant to the interface will help in the formation, maintenance, and repair of
interfacial tissue.
Electrospinning is an efficient technique to recreate the hierarchical structures
present in the ECM. Nanofibers made from collagen, their blends with other
polymers and hydroxyapatite have been found to favor tissue-specific cell response.
However, depth of cell infiltration and diffusion constraints are some of the major
concerns with this technique. Thus, refinements need to be introduced into the
existing electrospinning parameters to make scaffolds of larger size, with graded
structures and mechanical properties, and for co-spinning of cells and bioactive
molecules.

14.4 Limitations of Discrete Layers and Approaches for
Strengthening the Interface Using Continuous Gradients

Discrete layers can severely affect the interconnection between pores of two layers
at the interface. This can severely hinder cellular infiltration and migration into the
scaffold. The discontinuities at the scaffold interface could also negatively
influence the fluid flow between the two regions, which would in turn affect nutrient
and waste transport. Moreover, abrupt stress transfer can occur at the interface
and can result in stress concentrations which may weaken the scaffold and cause
delamination at the interface between two regions. The evolution to continuous
gradient scaffolds from biphasic scaffolds is schematically represented in Fig. 14.4 .
As such, there is a need for a strategy to design and build scaffolds with appropriate
continuous functional gradients to support interface regeneration.
Harley et al . [ 104 ] described a method called liquid phase co-synthesis to
fabricate a multilayered scaffold with a continuous gradual interface. The scaffolds
were made by interdiffusion of a type II collagen-glycosaminoglycan copolymer to
mineralized, type I collagen-glycosaminoglycan suspensions followed by freezing
at a constant rate and lyophilization. Liquid-phase co-synthesis produced an inter-
face across a zone of interdiffusion, inside which intermixing of the two

suspensions was obtained to form a soft continuous interface.
Bretcanu et al . [ 86 ] made a continuous gradient scaffold by casting a bioglass
slurry on preformed polyurethane sponge templates that were compressed at
different rates in an aluminum mold to obtain a continuous gradient in porosity.
The organic polyurethane foam was then burned out by sintering at high
temperatures. This simple method could be used for scaffolds with different
shapes and porosity profiles.