MICRO-AND NANOSPHERES FOR TISSUE ENGINEERING - Micro and Nanotechnologies in Engineering Stem Cells and Tissues - page 211

FIGURE 9.4 The use of micro- and nanospheres as building blocks to assemble into
macroscopic structures by either random packing or directed assembly of the spheres.
by the individual particles migrating from the treatment sites. 97 To address this
problem, efforts have been made to increase the cohesion of micro- and nanosphere-
based formulations at the implantation sites (e.g., by using glues or additional
interparticle cross-linkers). 97,98 Alternatively, sintered microsphere-based scaffolds
were developed by fusing densely packed PLGA 99 or chitosan 100 microspheres
together by thermal treatments. These scaffolds exhibited tailorable morphological
and compositional properties of the scaffolds, 99 controllable biomolecules release
profiles, 31,63 in vitro and in vivo biocompatibility, 101,102 and a degree of degradability
suitable for tissue engineering applications. 103
Directed assembly of micro- and nanospheres into cohesive macroscopic con-
structs has recently been advocated as a more sophisticated strategy to design
particle-based scaffolds by maximizing interparticle interactions (e.g., electrostatic,
magnetic, or hydrophobic interactions) as driving forces to induce self-assembly of
micro- and nanospheres. Specifically, colloidal gels have been developed recently
based on self-assembly of micro- or nanospheres directed by either electro-
static 35,104-106 or hydrophobic 107 interactions, which showed desired structural
integrity and mechanical stability in physiological conditions, 105 excellent inject-
ability and moldability, and capability of self-recovery after network destruction
because of the reversible physical cross-linking features that characterize these self-
assembling systems. 35,105,107 These physical gels showed great potential to be used
as injectable fillers for regenerative medicine by using minimally invasive surgery.
For example, Wang et al. prepared injectable colloidal gels made of oppositely
charged, dexamethasone-loaded PLGA nanospheres, which displayed a nearly zero-
order drug release profile in vitro and induced bone formation in vivo. 108 Similar to
electrostatic and hydrophobic interactions, magnetic force can also be used as a
powerful tool to trigger self-assembly of micro- or nanoscale building blocks to
generate integrated structures as tissue engineering scaffolds. 109,110 Interestingly,
instead of using magnetic micro- and nanospheres as building blocks, Ito et al.
recently developed magnetic nanosphere-labeled cells as structural units to form a