MICRO-AND NANOSPHERES FOR TISSUE ENGINEERING - Micro and Nanotechnologies in Engineering Stem Cells and Tissues - page 204

9.2 MATERIALS CLASSIFICATION OF MICRO- AND NANOSPHERES
With regard to applications in tissue engineering, micro- and nanospheres should
fulfill the basic requirements that apply to virtually all biomaterials, including
biocompatibility, biodegradability, nontoxicity of degradation products, and ease
of processing. In general, micro- and nanospheres can be categorized into polymeric,
ceramic, and composite materials.
Polymeric micro- and nanospheres have been studied most extensively for
applications in controlled delivery and tissue engineering since the 1970s, when
polymeric microspheres were initially introduced as drug delivery systems. The
advantages of polymers over inorganic biomaterials include the ease of processing,
high degree of control over the physicochemical properties (such as biodegradabil-
ity), and ease of functionalization and modification. Depending on their origin,
polymeric micro- and nanospheres can be classified as either natural or synthetic
polymers, both of which have their specific pros and cons.
Natural polymers are an important class of biomaterials in tissue regeneration
basically because of their intrinsic biocompatibility and biodegradability. Because
they are derived from natural organisms, natural polymers are generally character-
ized by an excellent biocompatibility, biodegradability, a negligible immunogenic-
ity, an abundant presence of side groups allowing for further chemical
functionalization, and the presence of cell-recognition motifs (in the case of
protein-based polymers, e.g., collagen, gelatin and fibrin). 12,21-23 Micro- and nano-
spheres made of natural polymers can be prepared by simple emulsion techniques in
which spheres of variable properties (size and morphology) can be obtained by
tailoring the emulsification process. 24,25 The resultant micro- and nanospheres are
widely accepted as desirable vehicles for drug or biomolecule delivery because of the
gentle gelling conditions that facilitate encapsulation of biomolecules and cells,
controllable release kinetics by fine-tuning the degradation of carriers, and ease of
functionalization. 26-29 Despite the favorable properties, several critical concerns
about natural polymers include (1) poor mechanical properties that hamper appli-
cations under load-bearing conditions, 21,22 (2) immunogenicity or the risk for disease
transfer for polymers extracted from allogeneic or heterogenous sources, 30 and (3)
poor control over physicochemical characteristics (e.g., molecular weight).
On the other hand, synthetic polymers, such as poly(lactic acid) (PLA) and poly
(lactic-co-glycolic acid) (PLGA), are also of considerable importance for regenerative
medicine applications owing to their biocompatibility, biodegradability, well-defined
physicochemical properties (e.g., molecular weight), defined mechanical properties,
ease of fabrication and modification, and the absence of the possibility to transfer
diseases. Micro- and nanospheres composed of synthetic polymers have been widely
investigated as delivery vehicles for therapeutic agents 31-33 and building blocks for
tissue engineering scaffolds. 34,35 However, drawbacks related to the use of micro- and
nanospheres made of synthetic polymers include the acidic degradation products,
hydrophobicity, degradation by autocatalysis, and low drug-loading efficacy. 36
To develop biomaterials of enhanced physicochemical and biological properties,
composite materials have gained considerable attention for tissue engineering