MICRO-AND NANOSPHERES FOR TISSUE ENGINEERING - Micro and Nanotechnologies in Engineering Stem Cells and Tissues - page 203

biomaterials of enhanced complexity and functionality that not only provide
architectural support for cell/tissue growth but also, more importantly, mimic the
complex interactions between cells and the extracellular matrix (ECM) to orchestrate
cellular behavior and induce functional tissue regeneration.
Micro- and nanospheres have drawn increasing interest in the field of
regenerative medicine during the past decade, which can be used as functional
components in novel biomaterials of improved functionality. Microspheres (here
defined as ranging in diameter from 1 to 1000

m) have been investigated for
biomedical applications for several decades, but studies on the application of
nanospheres (defined here as spheres with diameters between 10 and 1000 nm)
in tissue engineering only emerged in the past 10 years, thus reflecting the rapid
development of micro- and nanotechnology in the field of tissue engineering.
With respect to the use of micro- and nanospheres for tissue engineering and
regeneration, four major strategies can be discerned to introduce these spheres
as functional components to improve the performance of conventional bulk
biomaterials. First, micro- and nanospheres can be used for controlled delivery
of therapeutics, chemical agents, and even cells; the spheres act as delivery
vehicles because of their inherently small size and corresponding large specific
surface area. The size and morphology of micro- and nanospheres facilitate a
high drug-loading efficiency, a quick response to stimuli from the surrounding
environment, a high reactivity toward surrounding tissues in vivo,andahigh
diffusibility and mobility of drug-loaded particles. 4-12 Specifically, by incorpo-
rating spheres loaded with biomolecules of interest into a continuous matrix,
classical scaffolding biomaterials can release signaling molecules without
compromising the properties of the bulk scaffold. 4-6,13 Second, micro- and
nanospheres can be used to alter the mechanical performance of monolithic
scaffolds either by acting as porogens to create porosity in otherwise dense
scaffolds 14 or as reinforcement phase to improve the mechanical strength of
weak matrices. 15,16 Third, by creating a protective microenvironment inside the
spheres, micro- and nanospheres can be used as compartmentalized microscopic
bioreactors for dedicated biochemical processes. 17 For instance, micro- and
nanospheres can be used to induce formation of biominerals and subsequently
trigger mineralization of surrounding hydrogels to form self-hardening bioma-
terials. This strategy is inspired by the process of endochondral bone formation,
in which matrix vesicles function as microcapsules to create a compartmental-
ized environment for the nucleation and formation of bone mineral. 18 Fourth,
micro- and nanospheres can serve as building blocks to establish macroscopic,
shape-specific colloidal systems that can be used as injectable or moldable
scaffolds for tissue engineering. This bottom-up strategy for design and manu-
facture of biomaterials has recently been advocated as a promising method to
develop materials with a highly defined structure and precisely controlled
properties. 19,20
This chapter focuses on the most recent advances in research on micro- and
nanospheres aiming at improvement of the functionality and clinical efficacy of
traditional scaffolds for soft and hard tissue engineering.

m