DESIGNING NANOFIBROUS SCAFFOLDS FOR TISSUE ENGINEERING - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 465

growth of chondrocytes in vitro and an increase in fi ber diameter had no effect on
the proliferation of chondrocytes. The ineffi cient mass transfer of nutrients and
oxygen in a thick scaffold in static culture can lead to necrotic zones in the inte-
rior of scaffolds. Application of dynamic seeding techniques is an effective strat-
egy to overcome the problems associated with static culture and can enhance cell
proliferation and ECM synthesis [101].
GAGs play an important role in maintaining chondrocyte cell morphology,
differentiation, and function [180,250]. Two abundantly available natural poly-
mers, chitosan and alginate, are GAG mimics that have been explored for nanofi -
ber synthesis by electrospinning [251]. Bhattarai et al. reported the successful
proliferation and growth of chondrocytes on both these polymers [146,178].
Alginate nanofi bers were fabricated using PEO as an additive to reduce the
viscosity of the pure alginate solution and hence enable electrospinning. Their
in vitro studies demonstrated that cartilage chondrocyte-like cells (HTB-94)
seeded on the alginate scaffold were viable and maintained their morphology and
characteristic phenotype after 72 hours of culture [146]. Another advantage of
electrospun nanofi brous scaffold over bulk alginate scaffolds is that they do not
require any precoated adhesion proteins such as fi bronectin or arginine - glycine -
aspartic acid peptides [RGD] to facilitate cell adhesion [146]. Therefore, the
aforementioned studies indicated that alginate nanofi bers could be potential
scaffolding system for cartilage tissue engineering.
In a similar study, Bhattarai et al. assessed the cellular compatibility of chito-
san nanofi brous scaffolds using chondrocytes. Chondrocytes (HTB-94) seeded on
chitosan/PEO nanofi brous membranes exhibited a rounded morphology that is a
characteristic feature of chondrocytes [178]. In another study, Subramanian et al.
reported an increased elastic modulus (2.25 MPa) of electrospun chitosan mesh in
comparison to chitosan cast fi lm (1.19 MPa) [252] . Their results demonstrated
better cell attachment and proliferation with chondrocytes onto chitosan nanofi -
brous meshes when compared to chitosan cast fi lm. Therefore, these results dem-
onstrated the potential of chitosan nanofi brous matrices as scaffolds in cartilage
tissue engineering.
Electrospun synthetic biodegradable polymers have also been explored as
potential scaffolds for cartilage tissue engineering. Shin et al. [253] studied the
potential of PLGA electrospun nanofi brous scaffolds in cartilage regeneration.
This study demonstrated the effect of content ratio of two different polymers
(lactic acid/glycolic acid ratio) of PLGA on degradation and mechanical strength
of scaffold. In their studies, they reported that PLGA nanofi brous scaffolds
degraded in four to seven weeks, which is suitable to support cell and tissue devel-
opment in vivo . Further, they investigated the behavior of primary chondrocytes
on electrospun PLGA nanofi bers and the effect of intermittent hydrostatic
pressure on cell-seeded scaffolds. Their results demonstrated that electrospun
nanofi brous PLGA scaffolds were non-cytotoxic and promoted chondrocytic
proliferation and enhanced synthesis of ECM components. In addition, applica-
tion of intermittent hydrostatic pressure on cell-seeded scaffolds increased cell
proliferation and synthesis of collagen and proteoglycan [253].