ISSN 2075-1133, Inorganic Materials: Applied Research, 2011, Vol. 2, No. 1, pp. 85–90. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © A.Yu. Fedotov, V.S. Komlev, V.V. Smirnov, I.V. Fadeeva, S.M. Barinov, V.M. Ievlev, S.A. Soldatenkov, N.S. Sergeeva, I.K. Sviridova, V.A.Kirsanova,
S.A. Akhmedova, 2011, published in Materialovedenie, 2010, No. 7, pp. 41–46.
85
INTRODUCTION
Volumetric polymer foam structures are promising
for application as 3D matrices, on which cells (includ-
ing stem ones) can be cultured and subsequently
implanted in damaged tissues (osteal and cartilagi-
nous) for their regeneration [1, 2]. With time, the
matrix is gradually replaced by a de novo formed tis-
sue. This method, which has been actively developing
in medicine for the last decade, is known as tissue
engineering. The material of a matrix should be bio-
compatible with the body’s medium; have the kinetics
of biological degradation (resorption) corresponding
to that in the formation of new tissue; and be elastic for
supporting tight attachment to a recipient base and
filling of a defect, as well as osteoconductive, i.e.,
capable of maintaining cell vitality, physiological
flows, and vascularization. Furthermore, an addi-
tional requirement was recently formulated in the pro-
cess of clinical trials of one novel biopolymer—if a
material for repairing a defect is applied in a milled
form (granule, crumb, etc.), it is expedient to intro-
duce it in a complex with a binding agent to reduce the
risk of microtraumas to surrounding tissues and pre-
vent the material from going beyond the localization of
the defect in the postoperative period [3, 4]. We would
like to consider, as an example of the most prospective
materials, some highly porous hybrid composite mate-
rials (CMs) based on biopolymers—chitosan and gel-
atin, reinforced with calcium phosphate particles [5].
The composites are biocompatible and elastic, while
the reinforcing phosphates add the desired mechanical
and biological properties. This work presents the
results of studies on the technology of hybrid CMs,
reinforced with nanoparticles and granules of
hydroxyapatite (HA) and its carbonate-substituted
form (CHA), and their properties.
EXPERIMENTAL
Porous biopolymer matrices were fabricated by
blending a 5% acetic acid solution of medium-molec-
ular chitosan (50 to 190 kDa) and a 10% aqueous solu-
tion of gelatin in the chitosan-to-gelatin mass ratios of
100/0, 90/10, 70/30, 50/50, 30/70, 10/90, and 0/100
until a homogeneous blend was formed. Then a foam-
ing agent—ammonium carbonate—was added. The
resulting dense suspension was placed inside a poly-
ethylene cylinder-shaped mold (diameter of 12 mm,
height of 40 mm) and frozen until ice crystals were
formed at –18°C or –180°C. The frozen material was
subjected to sublimated drying to remove ice. The
dried samples were placed in ethyl alcohol for replac-
ing acetic acid residues contained in the sample with
alcohol. Then the samples were dried at 60°C in air
until the liquid phase was completely removed.
The initial HA and CHA powders were synthesized
by the reaction
Hybrid Composite Materials Based on Chitosan and Gelatin
and Reinforced with Hydroxyapatite for Tissue Engineering
A. Yu. Fedotov
a
, V. S. Komlev
a
, V. V. Smirnov
a
, I. V. Fadeeva
a
, S. M. Barinov
a
, V. M. Ievlev
b
,
S. A. Soldatenkov
b
, N. S. Sergeeva
c
, I. K. Sviridova
c
, V. A. Kirsanova
c
, and S. A. Akhmedova
c
a
Baikov Institute of Metallurgy and Materials Science, Russian Academy of Sciences, Moscow, Russia
e-mail: barinov@imet.ac.ru
b
Voronezh State University, Voronezh, Russia
c
Herzen Oncology Research Institute, Rosmedtekhnologii, Moscow, Russia
Received April 1, 2010
Abstract—The fundamentals of the technology are developed for the fabrication of hybrid composite chito-
san/gelatin–hydroxyapatite materials aimed for medical applications as porous matrices in regenerating
damaged bone tissues, and the properties of the above materials are investigated. They are elastic, having a
porosity of up to 90% and pores of up to 700 μm in size; possess controlled dissolution kinetics; contain up
to 90 wt % hydroxyapatite or carbonate-substituted hydroxyapatite in the form of nanodisperse powders or
granules with a size of up to 500 μm; and are characterized by no cytotoxicity. Their introduction into the site
of a bone defect considerably accelerates the process of regeneration in a bone tissue.
Keywords: biomaterials, composite materials, biopolymers, calcium phosphates, tissue engineering, oncology.
DOI: 10.1134/S2075113311010072