ORIGINAL RESEARCH PAPER
Enhancement of cell proliferation and differentiation
by combination of ascorbate and dexamethasone
in thermo-reversible hydrogel constructs
embedded with rabbit chondrocytes
Kun Na Æ Seong-Jun Choi Æ Sungwon Kim Æ Bo Kyung Sun Æ Dae Gyun Woo Æ
Hyung-Min Chung Æ Keun-Hong Park
Received: 25 January 2007 / Revised: 5 May 2007 / Accepted: 8 May 2007 / Published online: 23 June 2007
Ó Springer Science+Business Media B.V. 2007
Abstract The effects of inducible materials
(dexamethasone and ascorbate) on chondrogenic
differentiation of rabbit chondrocytes have been
examined. A hydrogel construct containing dexa-
methasone and ascorbate up-regulated gene expres-
sion of the cartilage matrix component of collagen to
give three times the collagen content per construct at
day 56 as compared to controls. Alcian Blue and
Safranin-O staining revealed that these constructs also
had formed more hyaline cartilage than other hydro-
gel constructs.
Keywords Ascorbate Á Cartilage Á Chondrocytes Á
Dexamethasone Á Hydrogel
Introduction
In principle, chondrocyte dedifferentiation can be
reversed by transferring cells into an environment
that supports a spherical morphology such as in
pellets, polymer gels, or three dimensional (3D)
scaffolds (Giannoni et al. 2005; Malda et al. 2004;
Stewart et al. 2000). In three-dimensional culture
systems, hydrogels have been particularly successful
as suitable materials for cell delivery because they are
water-saturated, turgid networks that mimic the three-
dimensional environment of various cells in native
cartilaginous tissues. Additionally, many hydrogel
formulations can be cross-linked in situ and, thus, can
be used in minimally invasive surgical procedures
(Hoemann et al. 2005; Barbucci et al. 2002). Specific
agents added to hydrogels can decrease the time
needed to expand the chondrocyte populations, even
when isolated from elderly individuals.
Ascorbic acid, for example, causes collagen
hydroxylation via modification of prolyl and lysl
residues (Wang et al. 1989). Connective tissue cells,
including chondrocytes, cultured in absence of
ascorbic acid result in collagen under-hydroxylation
with impaired collagen secretion. Additionally,
glucocorticoids, dexamethasone (DEX), can promote
the differentiation of chondrocytes and maintain the
The first two authors Kun Na and Seong-Jun Choi equally
contributed to this work.
K. Na
Division of Biotechnology, The Catholic University
of Korea, 43-1 Yokkok2-dong, Wonmi-gu,
Bucheon 420-743, Republic of Korea
S.-J. Choi Á H.-M. Chung Á K.-H. Park (&)
College of Medicine, Pochon CHA University, Cell and
Gene Therapy Research Institue, 606-16, Yeoksam
1-dong, Kangnam-gu, Seoul 135-081, Republic of Korea
e-mail: phd0410@hanmail.net
S. Kim
Biomaterials Research Center, Korea Institute of Science
and Technology, 39-1 Haweolgog-dong, 136-791
Sungbook-gu, Seoul, Republic of Korea
B. K. Sun Á D. G. Woo
Chabiotech Co., Ltd, Yeoksam 1-dong, Kangnam-gu,
Seoul 135-081, Republic of Korea
123
Biotechnol Lett (2007) 29:1453–1457
DOI 10.1007/s10529-007-9420-8