Crimson Publishers-Poly(Glycerol-Sebacate) Elastomer: A Mini Review

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Introduction
Regenerative medicine is an emerging field that uses different
types of biomaterials consisting of polymers, ceramics, metals
and their composites to restore or maintain the whole or partial
tissues/organs. Some part of these materials mentioned above
has potential to be used in clinical field owing to their superior
properties, while another part needs further development. Both
natural and synthetic polymeric materials are of enormous interest
in the clinic due to their biocompatibility, mechanical properties,
ECM like structures, degradation parallel to ECM formation etc.
Poly (glycerol-sebacate) (PGS) is a synthetic, biodegradable,
thermo set and tough polymer first reported in 2002 by Wang et
al. [1] and proposed for soft tissue engineering. It is emphasized
in the first reported paper which introduces PGS to the scientific
literature that it is cheap, bio-resorbable, bio degradable and has
non-toxic degradation products [1]. Upon the discovery of PGS,
many research studies in biomedical field had been launched by
using this polymer including the development of polymer blends,
composites, scaffold material for tissue engineering, adhesives,
drug delivery system, sealants and coating materials [2]. PGS have
mostly been proposed for soft tissue as a scaffold material. When
the mechanical properties of soft tissues frequently studied in the
context of tissue engineering are considered, Young Modulus values
are observed between 0.1 and 11.1MPa [3]. As for the mechanical
properties of PGS recorded in the previous studies, it seems to be
extremely compatible with soft tissues regarding to its tunable
mechanical properties via cross linking [2,4]. Despite being suitable
for soft tissue, we have also found examples in the literature for
hard tissue repair, often combined with osteo conductive materials
[5-7]. Moreover, the combination of this material with β-tricalcium
phosphate ceramics was proposed for guided bone regeneration in
our previous study [8].
The main purpose of drug delivery studies is to distribute
the drugs to a local target and sustain the therapeutic effects
of drugs within the therapeutic frame and reduced toxicity [9].
Many damaged organs and tissues in the body can be accepted as
a target. Therefore, drug delivery has a wide range of application
area from anticancer therapy and contraceptive methods, to
infectious disease [10]. In the field of drug delivery, the local
distribution of target drugs/molecules is in close relationship
with the degradation profile and the rate of the matrix. Studies
conducted on the degradation of PGS have found that PGS degrades
via surface erosion and it is understood that surface degradation is
due to the breakage of the ester bonds [11]. PGS has been proposed
as a matrix for anticancer drug encapsulations by Sun et al. [12].
In another study, berberine and chlorhexidine were encapsulated
into the PGS as an active ingredient for periodontal regeneration by
Deng et al. [13].
Yet another application of PGS includes their usage as tissue
adhesives. There has been an increasing demand in the clinic
for though biodegradable polymer adhesives that can cover the
mechanical deformations while continuing to adhere to the tissue
[14]. One of the possible reasons of demand can be disadvantages
of conventional sutures and staples such as absence of elastic
behavior and presence of toxicity or inflammatory effects. One
of the other possible causes is that the elastic properties of
conventional materials cannot adapt to every tissue [6]. Chen et al.
Atakan Tevlek1
and Halil Murat Aydin2
*
1
Institute of Science and Engineering, Bioengineering Division, Hacettepe University, Turkey
2
Environmental Engineering Department & Bioengineering Division and Centre for Bioengineering, Hacettepe University, Turkey
*Corresponding author: Halil Murat Aydin, Environmental Engineering Department & Bioengineering Division and Centre for Bioengineering,
Hacettepe University, 06800, Ankara, Turkey, Tel: +903-1229-7 780-0130; Fax: +9031-2299-2053; Email:
Submission: August 31, 2017; Published: December 15, 2017
Poly(Glycerol-Sebacate) Elastomer: A Mini Review
Ortho Surg Ortho Care Int J
Copyright © All rights are reserved by Halil Murat Aydin.
CRIMSONpublishers
http://www.crimsonpublishers.com
Abstract
Poly glycerol sebacate (PGS) is a synthetic polymer widely known in the field of tissue engineering and has achieved remarkable attention due to its
desired properties such as having surface degradation and elastomeric behavior. Different synthesis methods based on pre-poly condensation step and
crosslinking have been defined for PGS production till now. Thanks to its physico-chemical, mechanical, thermal and morphological properties; it has
been proposed for numerous tissue engineering applications ranging from soft to hard tissue by researchers. Both in-vitro and in-vivo many research
studies have been carried out not only upon PGS but also its composite forms. In addition, different production techniques and characterization methods
have been pursued. Within the scope of this mini review article; the importance of PGS along with its discovery, production techniques, characterization
and applications were described and explained.
Mini Review
ISSN 2578-0069

How to cite this article: Tevlek A, Aydin HM. Poly(Glycerol-Sebacate) Elastomer: A Mini Review. Ortho Surg Ortho Care Int J. 1(2). OOIJ.000507. 2017.
DOI: 10.31031/OOIJ.2017.01.000507
Orthoplastic Surgery & Orthopedic Care International Journal
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[15] developed a synthetic tissue sealant from (PGS) and poly lactic
acid (PLA) copolymer as an alternative to fibrin or collagen based
adhesives to eliminate their viral risks. Mahdavi et al. [16] has
proposed a new generation tissue adhesives made of poly (glycerol-
co-sebacate acrylate) to overcome the limitation of conventional
materials due to adjustable elasticity through cross linking density.
Many biomaterial candidates have been combined with one
another up to date to increase their mechanical or chemical
properties or to cover their deficiencies. PGS is also one of these
materials. PGS-fumarate and hydroxyapatite combination was
proposed by Bodakhe et al. [17] to produce injectable, highly
bioactive and biocompatible nano composites. The addition of
hydroxyl apatite has been reported to increase ultimate strength
of the structure. In another study, multi-walled carbon nanotube
(MWCNT)/poly(glycerol-sebacate-citrate) (PGSC) elastomer
composite was reported by Lui et al. [18]. The addition of carbon
nanotubes was found to improve the strength and the modulus
while degradation was reduced.
ProductionandCharacterizationofPGSasaBiomaterial
PGS is produced by combining glycerol and sebacic acid
monomers with specific ratios. Hydroxyl groups of glycerol and
carboxylic acids of sebacic acid undergo polycondensation reaction
without any catalysts [19]. According to the first published article
by Wang et al. [1] two step production protocols was needed to be
followed: polycondensation and crosslinking. Equimolar mixtures
of each starting monomers (1M of glycerol and sebacic acid) were
reacted at 120 °C under argon atmosphere for 24 hours before the
pressure was reduced from 1 Torr to 40m Torr. Consequently, the
pre-polymer was exposed to 40m Torrvacuum at 120 °C for 48hours
for cross linking to occur [1]. A group of scientist investigated the
alternative synthesis methods of PGS by changing molar ratio,
curing temperature and cross linking parameters [15,20]. Also
in our previous study, we demonstrated a facile PGS production
method via microwave-assisted pre-polymerization without using
a gas, catalyst or vacuum [21].
PGS, as a biomaterial, needs to be characterized to identify
its possible application areas. For this purpose, physicochemical,
mechanical and thermal properties of PGS together with its
degradation and biocompatibility were investigated in detail [2].
PGS can be defined as transparent, almost odorless and colorless
polyester. Wang et al. [1] characterized the chemical structure of
PGS by FTIR analyses. The peaks differ in the spectra with respect
to its crosslinking density, curing temperature and curing time [22].
According to the Nuclear Magnetic Resonance (NMR) spectroscopy
analyses, the hydroxyl groups were bonded covalently to the
carbon backbone, which provides hydrophilicity. Hydrogenbonding
interactions between the hydroxyl groups, on the other hand,
represents elasticity [1]. The hydrophilicity of the structure can be
tunable by changing the crosslink parameters. As the curing time
was increased, hydrophilicity was reduced due to the removal of
hydroxyl groups from the structure [23].
The average Young modulus of PGS was calculated between
0.02 and 1.2MPa and ultimate tensile strength was found greater
than 0.5MPa [4,20,24]. The mechanical properties can be adjusted
by changing the curing temperature, curing time and molar ratio
of the monomers [25]. Thermal properties of PGS can be studied
by Differential Scanning Calorimetry (DSC) analysis. Thermal
properties of PGS depend on the transition temperature (Tg
) of the
amorphous phase and melting temperature (Tm
) of the crystalline
phase as it is a partially semi-crystalline polymer. As stated in the
literature, PGS exhibits a Tg
at -37 °C with broad melting transition
at temperature ranging from -20 °C to 40 °C according to the DSC
diagram [26].
Crystallinity and morphology of PGS can be revealed by X-Ray
Diffraction (XRD) analysis. PGS shows a broaden peak in the
spectra. The main diffraction peak is centered at 19.8 °C due to the
doped sebacate in the structure. It was observed that the intensity
of the diffraction peak decreased as the amount of sebacic acid in
the structure increased. On the other hand once the curing time
and temperature was increased, the crystallinity of PGS decreased
[22,27]. The degradation mechanism of PGS can be defined as the
surface degradation due to the cleavage of the ester bonds in the
structures [11]. Wang et al. [1] noted on the first article on PGS that
in-vitro and in-vivo degradation of PGS differs. In-vitro degradation
of PGS was measured as 17.6% weight loss while it was completely
absorbed in-vivo in a study that lasted 60 days. The degradation
kinetics can be affected by production parameters such as curing
time and temperature. For instance, if crosslink density increases
in proportion with curing time or heat, the degradation kinetics
decreases [1,4].
Biocompatibility of PGS is one of its superior properties
originated from its components: glycerol and sebacic acid approved
by FDA [28]. Nevertheless, its biocompatibility was investigated
by many researchers [29-31]. Although there is still no study
emphasizing the toxicity of PGS, Chen et al. [32] reported that the
local acidic environments encountered due to the hydrolysis of the
ester groups releasing carboxylic acid [32]. Therefore, a number of
surface functionalization methods have been suggested to enhance
the cell migration, adhesion, differentiation and proliferation such
as surface coating with a biomolecule, grafting of hydrophilic
groups or enzyme treatment [33,34,50].
Biomedical Applications of PGS
As summarized above, PGS has numerous advantages compared
to other existing synthetic bio-degradable polymeric materials.
Its elastic and biocompatible nature has attracted great attention
of the researches who work in biomedical field. In the light of
increasing demand on biomedical materials, researchers have been
investigating the PGS in many different areas listed on Table 1.
Conclusion
PGS has a pivotal role in biomedical arena regarding to its
elasticity, biocompatibility and biodegradability. Research studies
are ongoing to develop PGS based material both alone and in

DOI: 10.31031/OOIJ.2017.01.000507
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Ortho Surg Ortho Care Int JOrthoplastic Surgery & Orthopedic Care International Journal
combination with other materials in different forms and sizes. In
addition to the technical specifications, providing a cheap, practical
production method that does not require a lot of equipment will
lead researchers to develop new biomaterials in the future.
Table 1: Biomedical application of PGS.
Material Application Reference
PGS Cardiac Tissue Engineering [4,35,36]
PGS/Bioactive Glass Bone Tissue Engineering [5]
PGS Bone Tissue Engineering [7]
PGS/β-TCP Bone Tissue Engineering [8,37]
PGS Drug Delivery [12,13]
PGS/PLA
Surgical Sealants/Tissue
Adhesives
[15]
PGS/Acrylate
Surgical Sealants/Tissue
Adhesives
[16]
PGS/Fumarate/HA Bone Tissue Engineering [17]
PGS Cartilage Tissue Engineering [20]
PGS Shape Memory [26]
PGS Nerve Tissue Engineering [31]
PGS Soft Tissue Engineering [38,39]
PGS/PCL Cardiac Tissue Engineering [40]
PGS/PBS-DLA Cardiac Tissue Engineering [41]
PGS/Ɛ-PCL Cornea Tissue Engineering [42]
PGS Retina Tissue Engineering [43]
PGS/HA Bone Tissue Engineering [44]
PGS/PMMA-Gelatin Nerve Tissue Engineering [45]
PGS/Curcumin Drug Delivery [46]
PGS Coating Material [47]
Acr-PGS 3D Printing [48]
PGS/Urethane/
Cellulose
Shape Memory [49]
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