Control and Monitoring of Scaffold Architecture for Tissue Engineering - Biomaterials Fabrication and Processing - page 71

The authors' group has combined the application of mechanical and biochemical stimuli by devel-
oping a mechanoactive scaffold. This study has shown that in the presence of in vitro physiological
loading regimes and release of calcium channel agonists incorporated in poly (L-lactic acid) (PLLA)
scaffolds, the expression of collagen I and osteopontin and osteoid calcifi cation were enhanced,
when compared with controls. 23,24 These results indicate that agonist-encapsulated scaffolds can be
used in the presence of load to enhance the production of load-bearing engineered tissue.
Scaffolds play a pivotal role in converting isolated cells to functional tissues because they ini-
tially endow cells with temporary shelter for anchoring, adhering, and settling down. The require-
ments of supporting the cell to grow into a functional tissue make it essential for the scaffold to
have several unique features. The fi rst one is obviously biocompatibility. High porosity is also a
prerequisite, to provide space for the cells to settle down, generate ECM, and to guarantee an effec-
tive diffusion of nutrients, metabolites, biological cues, and gases across the scaffolds during the
in vitro maturation. The porous structure also facilitates angiogenesis after implantation, thus blood
vessels can grow and supply oxygen and nutrients to the center of the construct. 25 In addition to an
appropriate porosity, the scaffold must display the required mechanical integrity to maintain the
predesigned tissue structure and to guarantee a suitable performance when it is subjected to the
local strain after implantation. The ability to degrade in the biological environment by either enzy-
matic or hydrolytic reaction is another feature of the scaffold. The degradation and elimination rate
of the temporary template should correspond with the rate of tissue turnover.
When the fi nal goal is to achieve a functional tissue construct, providing only the essential
requisites for cell survival and proliferation is not enough. In their natural environment, the cells
are integrated in tissues that display specifi c architectures usually optimized for specialized func-
tions. Consequently, it is not surprising that several studies have shown that the cell behavior is
highly infl uenced by the architecture of the scaffolds. These studies have shown that rather than
just responding to the chemical composition of the scaffolds, the cells actually react to structural
parameters, such as surface topography and the stiffness, 26,27 nanotopography, 28,29 fi ber diameter, 30
and microgeometry. 31,32 Some authors have even shown that it is possible to direct cell migration to
specifi c areas of scaffolds by using micropatterning techniques to create micropaths with specifi c
architecture. 33,34 Nevertheless, one has to bear in mind that the possibility of extrapolating these
studies to different contexts is fairly limited because they report the behavior of a particular cell
type in a particular type of scaffold. The establishment of standard generalized cell behavior in a
well-defi ned context is at the moment virtually impossible because of the high amount of variability
stemming from the conditions used in different laboratories.

3.3 SCAFFOLDS FOR TISSUE ENGINEERING

3.3.1 M ATERIALS
The materials used to fabricate scaffolds for TE are derived either from synthetic polymers, mainly
from polyester family, or from natural materials, for example, collagen and chitosan. The mechani-
cal properties and structural properties of these materials can be tailored by adjusting the molecular
weight, crystallinity, and the ratio of comonomers in the copolymers. 35-38

3.3.1.1 Synthetic Polymers

Poly(glycolic acid) (PGA), poly(lactic acid) (PLA), and their copolymers poly(lactic acid- co -glycolic
acid) (PLGA) are a family of linear aliphatic polyesters, which are most frequently used in TE. 39 These
polymers are among the few synthetic polymers approved by the U.S. Food and Drug Administration
(FDA) for certain human-clinical applications. 40 They degrade through hydrolysis of the ester bonds, 41
and the ultimate products of their degradation are the monomers lactic and glycolic acids, which are
further transformed into water and carbon dioxide in well-defi ned metabolic pathways. 42 Several stud-
ies have revealed that they are biocompatible and that their presence is well-tolerated in vivo . 43,44