Biomimetic ECM Scaffolds Prepared from Cultured Cells - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 240

should mimic the functional and structural characteristics of the native
ECM [6-7]. Native ECM is a complex network composed of collagen,
fi bronectin and other proteins, all of which are interlaced with proteogly-
cans [8]. ECM not only serves as a supporting material but also acts to
regulate cellular functions, such as cell proliferation, migration and dif-
ferentiation [9]. Moreover, ECM can modulate the signal transduction
activated by various bioactive molecules, such as growth factors and
cytokines [10].
Synthetic biodegradable polymers such as polylactide (PLA), poly-
glycolide (PGA), and poly(lactide-co-glycolide) (PLGA), and natural
polymers such as collagen, chondroitin and hyaluronic acid have been
frequently used to prepare porous scaffolds [11, 12]. However, synthetic
polymers are limited by their biological inertness and the acidic moieties,
residual catalysts and microscale particulates that accompany degradation
[14, 15]. By using isolated natural polymers, it is diffi cult to reconstruct a
scaffold that has the same composition as that of an in vivo ECM because
native ECM is composed of many kinds of proteins and has very intricate
structures. Although many researchers have been trying to identify the
proteins in ECMs in vivo , there remain a number of unidentifi ed proteins
[15]. Due to these diffi culties, acellular matrices have been prepared from
decellularization of tissues and oragns and used for tissue engineering.
Decellularization of tissues and organs, including small intestinal sub-
mucosa, heart valve, blood vessel, skin, nerve, tendon, ligament, urinary
bladder, vocal fold, amniotic membrane, heart, liver and lung, have been
reported [16-23]. The scaffolds obtained from decellularized tissues and
organs offer the advantage of maintaining the structures of their respective
tissues and organs. However, they suffer from problems of autologous tis-
sue/organ scarcity, host responses and pathogen transfer when allogenic
and xenogenic tissues and organs are used. Use of cultured cells is an alter-
nate way to fabricate ECM scaffolds. ECM scaffolds derived from cultured
cells can be prepared from various types of cells by different cell culture
methods [24-27]. Cultured cells offer several advantages compared with
animal tissues [28]. First, cultured cells can be screened for pathogens and
then maintained in a pathogen-free condition for ECM harvesting. Second,
cell-derived ECM scaffolds may provide the desired geometry and poros-
ity without the limitation of poor cell penetration that can occur during
the repopulating of decellularized native tissues. Third, the use of in vitro
cultured cells provides the fl exibility of mixing ECM samples that have
been harvested from different cell types. Furthermore, another important
advantage of cell-derived ECM scaffolds is that they can be prepared from
autologous cells to generate autologous ECM (aECM) scaffolds because
autologous cells can be isolated from patients and then expanded in labo-
ratories. In this chapter, porous ECM scaffolds that are prepared from in
vitro cultured cells by using removable templates will be the focus [29, 30].