INTEGRATING TOP-DOWN AND BOTTOM-UP SCAFFOLDING TISSUE ENGINEERING APPROACH FOR BONE REGENERATION - Micro and Nanotechnologies in Engineering Stem Cells and Tissues - page 144

6.3 BONE REGENERATION STRATEGIES AND TECHNIQUES
Scaffolds need to mimic the natural structure of regenerated tissue to obtain optimal
regeneration of biological functions. From a perspective of tissue engineering, cells,
ECM, cell-matrix interactions, and bioactive factors should be involved to achieve
the regenerated functions. For the components mentioned, an appropriate three-
dimensional (3D) scaffold is an essential component for a tissue engineering strategy
because scaffolds provide physical and mechanical support, spatial structure, and an
adequate biochemical environment for cell behavior. 10 Scaffolds applied in TE need
essential properties, including pore size, porosity, mechanical properties, and signal
presentation.
Bone is a dynamic, highly vascularized tissue with hierarchic structure in a 3D
configuration. 15 Therefore, the ideal scaffold should mimic the bone structure and
provide a 3D microenvironment for growing new tissue in the scaffold. However, the
coordination of all of these key components in an optimal spatial and time-dependent
fashion will affect the ultimate results of regenerated tissues. There are many
strategies or techniques for making bone constructs for tissue regeneration. From
a fabrication perspective, these strategies can be generally implemented in two
approaches: top down and bottom up.
6.3.1 Top-Down Tissue Engineering
6.3.1.1 Concept Since its emergence in the 1980s, 1,25 TE began to develop
different approaches for tissue regeneration. The top-down approach represents
the most traditional and typical one. Top-down tissue engineering approach gener-
ally uses well-defined porous scaffolds with tailored properties and signals as a
template to induce desired cell response, leading to engineered tissues and organs.
Specifically, to construct engineered bones, bone-forming cells or stem cells are
seeded onto prefabricated porous scaffolds with controlled release of growth factors
to induce bone formation. The essential properties of the scaffold include porosity,
interconnectivity and pore size, mechanical strength, and biodegradability. Scaffolds
as a template should possess similar functions to natural ECM. Scaffolds must
possess a fully interconnected porous structure and open macropores for efficient
nutrient and metabolite transport. The pores also facilitate the neovascularization of
the construct from the surrounding tissue at the same time. However, the porosity
will affect the mechanical properties that are required to balance the degradability of
the scaffold. The mechanical properties of the implanted scaffold should ideally
match those of living bone, so that no stress shielding or compression or deformation
of the scaffold by the surrounding tissues takes place. 26-28 Therefore, the extent of
porosity should be balanced with mechanical properties so that they both meet the
demands of a specific regenerating tissue. To further enhance cellular adhesion and
proliferation on the scaffold, the surface could be modified to be osteoconductive.
Many different cell-interacting ligands, such as the RGD cell-adhesive ligand, could
be grafted to the scaffold to provide biological cues for cell growth. The scaffolds
may be used to load growth factors or to serve as a delivery vehicle or reservoir for