International Journal of Biological Macromolecules 64 (2014) 11–16
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International Journal of Biological Macromolecules
jo ur nal homep age: www.elsevier.com/locate/ijbiomac
Bioactivity and biocompatibility of a chitosan-tobermorite
composite membrane for guided tissue regeneration
A.P. Hurt, G. Getti, N.J. Coleman
∗
School of Science, University of Greenwich, Chatham Maritime, Kent ME4 4TB, UK
a r t i c l e i n f o
Article history:
Received 22 September 2013
Received in revised form 7 November 2013
Accepted 22 November 2013
Available online 1 December 2013
Keywords:
Chitosan
Tobermorite
Bioactive
a b s t r a c t
A polymer-mineral composite membrane of the mucopolysaccharide derivative, chitosan, and calcium
silicate hydrate phase, tobermorite, was prepared by solvent casting and characterised by scanning
electron microscopy (SEM) and Fourier Transform infrared spectroscopy (FTIR). The bioactivity and bio-
compatibility of the chitosan-tobermorite composite were evaluated in vitro with respect to its potential
for use as a biodegradable guided tissue regeneration (GTR) membrane. The in vitro bioactivity of the
composite was confirmed by the formation of crystalline substituted hydroxyapatite on the surface of
the embedded tobermorite particles in simulated body fluid. The presence of the composite membrane
was found to enhance the growth of MG63 human osteosarcoma cells by up to 30%. The findings of this
initial study have indicated that this novel chitosan-tobermorite composite may be a suitable material
for GTR applications.
© 2013 Published by Elsevier B.V.
1. Introduction
Chitosan is the partially N-deacetylated derivative of chitin,
a structural mucopolysaccharide obtained on an industrial scale
from the shells of crustaceans [1,2]. The structure of chitosan, a
basic linear copolymer of N-acetylglucosamine and glucosamine, is
shown in Fig. 1a. Chitosan affords many advantages over synthetic
petroleum-based polymers as it is a readily renewable resource
which is edible, non-toxic, non-antigenic, biodegradable, biocom-
patible, haemostatic and antimicrobial [1,2]. It is readily processed
into membranes, gels, beads, mats, fibres and foams by a range
of techniques including: solvent casting; freeze-drying; electro-
spinning and supercritical fluid processing [3–9]. Current and
prospective applications of chitosan include: tissue engineering
scaffolds; wound dressings; resorbable sutures; medical textiles;
artificial skin; drug delivery systems; pharmaceuticals; contact
lenses; cosmetics; food packaging materials; and water filtration
media [1–10].
Chitosan is one among the numerous biocompatible biodegrad-
able polymeric materials (such as poly(glycolic acid), poly(lactic
acid), poly(caprolactone) and poly(urethane)) which have been
evaluated as scaffold materials for in vitro and in situ bone and peri-
odontal tissue engineering [1–11]. A major advantage of chitosan as
a substrate for bone tissue regeneration is that its structure resem-
bles those of glycosaminoglycans which are principal components
of bone extracellular matrix (ECM) [5–7]. Disadvantages of chitosan
∗
Corresponding author. Tel.: +44 07980 017088.
E-mail address: nj coleman@yahoo.co.uk (N.J. Coleman).
in these applications are that it is mechanically weak and lacks suffi-
cient bioactivity to induce initial rapid bone regeneration; however,
both of these problems can be addressed by reinforcing the chi-
tosan with finely divided osteogenic mineral phases to improve
mechanical strength and stimulate bone tissue formation [3–7]. To
date, candidate tissue scaffold composites of chitosan blended with
hydroxyapatite [3,7], -tricalcium phosphate [5], silica [6,12] and
bioactive glass [4] have been reported in the literature to possess
superior mechanical and osteogenic properties relative to those of
pure chitosan.
The development of bioactive membranes for guided tissue
regeneration (GTR) of periodontal structures is an area of increas-
ing interest in the treatment of periodontitis, an infectious disease
that destroys the tooth-attachment apparatus [8,11]. During the
progression of periodontitis, the epithelial tissue detaches from the
tooth, the periodontal ligament (PDL) disconnects and the alveolar
bone tissue is resorbed (as shown in Fig. 2a). Traditional treatment
of this condition involves the debridement and cleaning of the root
surfaces without the restoration of the compromised periodontal
attachment apparatus (i.e. PDL and alveolar bone). Epithelial cells,
which migrate approximately ten times faster than other peri-
odontal tissues, then grow alongside the tooth root and prevent
the re-establishment of the PDL and alveolar bone at the defect
site. GTR involves the use of a biocompatible membrane to exclude
the fast-growing epithelial and gingival tissues from the exposed
root and allow the more slow-growing bone and PDL tissues to
regenerate (as shown in Fig. 2b). Canine models have indicated
that chitosan GTR membranes enhance the re-establishment of the
PDL and alveolar bone compared with conventional treatment of
periodontal defects [13–15]. Improvements in the performance of
0141-8130/$ – see front matter © 2013 Published by Elsevier B.V.
http://dx.doi.org/10.1016/j.ijbiomac.2013.11.020