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Polyol-based	biodegradable	polyesters:	A	short
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DOI:	10.1515/revce-2015-0035
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*Corresponding author: Mat Uzir Wahit, Enhanced Polymer 
Research Group (EnPRO), Faculty of Chemical Engineering, 
Department of Polymer Engineering, Universiti Teknologi Malaysia 
(UTM), 81300 Johor Bahru, Johor, Malaysia, 
e-mail: mat.uzir@cheme.utm.my; and Centre for Composites (CfC), 
Institute of Vehicle System and Engineering (IVeSE), Universiti 
Teknologi Malaysia (UTM), 81300 Johor Bahru, Johor, Malaysia
Weng Hong Tham and Tuck Whye Wong: Enhanced Polymer 
Research Group (EnPRO), Faculty of Chemical Engineering, 
Department of Polymer Engineering, Universiti Teknologi Malaysia 
(UTM), 81300 Johor Bahru, Johor, Malaysia
Mohammed Rafiq Abdul Kadir: Medical Implant Technology Group 
(MEDITEG), Faculty of Biomedical Engineering and Health Science, 
Universiti Teknologi Malaysia (UTM), 81300 Johor Bahru, Johor, 
Malaysia
Onn Hassan: Faculty of Chemical Engineering, Universiti Teknologi 
Malaysia (UTM), 81300 Johor Bahru, Johor, Malaysia
Weng Hong Tham, Mat Uzir Wahit*, Mohammed Rafiq Abdul Kadir, Tuck Whye Wong 
and Onn Hassan
Polyol-based biodegradable polyesters: a short 
review
DOI 10.1515/revce-2015-0035
Received May 30, 2015; accepted October 15, 2015
Abstract: Catalyst-free thermal polyesterification has 
recently emerged as a potential strategy for designing 
biodegradable thermoset polymers, particularly polyol-
based polyesters for biomedical applications. These 
thermoset polyesters are synthesized through polycon-
densation of polyol and polyacid without the presence 
of catalyst or solvents. The mechanical properties, deg-
radation rates, crystallinity, hydrophilicity, and biocom-
patibility can be controlled by adjusting the monomer 
feed ratios and curing conditions. These polyesters often 
degrade via surface erosion that allows the polymers 
to maintain structural integrity throughout hydrolysis. 
Additionally, polyol-based polyesters demonstrated 
good biocompatibility as non-toxic catalysts and/or sol-
vents involved in the reaction, and the monomers used 
are endogenous to human metabolism which can be 
resorbed and metabolized in various physiological path-
ways. This review summarizes the polyol-based biode-
gradable polyesters that were synthesized by catalyst-free 
polyesterification.
Keywords: biodegradable; elastomers; polyol; synthetic 
polyesters.
1 Introduction
Tissue engineering offers a method to repair and/or 
replace damaged tissues through the combination of cells, 
scaffolds, and biomolecules (Langer and Vacanti 1993, 
Puppi et al. 2010, You and Wang 2011). Recent researches 
suggested that tissue engineering scaffolds should well 
match the mechanical properties of the corresponding 
natural tissues (Lee and Shin 2007, Barrett and Yousaf 
2009, Chen et al. 2012). Research and development of syn-
thetic polymers for potential use as scaffold materials is a 
challenging task because many diverse biological materi-
als with unique mechanical characteristics exist through-
out the human body (Chandran 1992, Dahms et al. 1998, 
Shepherd and Seedhom 1999, Gosline et al. 2002, Monson 
et al. 2003, Puskas and Chen 2004, Thambyah et al. 2006, 
Balguid et al. 2007, Tran et al. 2009, Bouten et al. 2011).
In the past decade, thermoset biodegradable poly-
esters have been extensively investigated due to their 
potential in soft-tissue engineering where the mechani-
cal properties of the designed scaffolds can be tailored to 
mimic those of soft tissues (Table 1). The strength and flex-
ibility of a scaffold have been shown to enhance cellular 
behavior and/or improve cell proliferation (Niklason et al. 
1999, Kim and Mooney 2000, Seliktar et al. 2003). Since 
crosslinked polyesters have the ability to recover from 
deformation, the resulting scaffolds are expected to be 
able to transfer stress to the new developing tissues while 
maintaining structural integrity from deformation without 
mechanical irritation (Wang et al. 2002, Yang et al. 2004, 
Migneco et al. 2009, Tran et al. 2009). Additionally, among 
the synthetic polymers, thermoset polyesters are one such 
class of materials that are biocompatible, hydrolytically 
degradable, and elastomeric and have demonstrated 
tunable mechanical properties and rate of degradation 
(Webb et al. 2004, Amsden 2007, Barrett and Yousaf 2009, 
Shi et al. 2009, Serrano et al. 2010).
It is well known that biodegradable polyesters can 
be prepared as either thermoplastic or thermoset mate-
rials (Grijpma et al. 1991, Sipos et al. 1995, Jeong et al. 
2004, Webb et al. 2004, Zhang et al. 2004, Amsden 2007, 
Barrett and Yousaf 2010). The traditional approach in 
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2      W.H. Tham et al.: Polyol-based biodegradable polyesters
Table 1: Mechanical properties of selected human tissues.
Tissue   Young’s modulus (MPa)   Maximum strain (%)  References
Bovine elastin   1.1   –  Gosline et al. (2002)
Collagen fiber   100   50  Chandran (1992)
Relaxed smooth muscle   0.006   300  Chandran (1992)
Contracted smooth muscle   0.010   300  Chandran (1992)
Human bladder   0.25   69  Dahms et al. (1998)
Knee articular cartilage   2.1–11.8   –  Shepherd and Seedhom (1999), Thambyah et al. (2006)
Human ascending aorta   0.069   81  Puskas and Chen (2004)
Human inferior cava vein   1.17   84  Puskas and Chen (2004)
Ulnar peripheral nerve   9.8–21.6   8–21  Tran et al. (2009)
designing thermoplastic polyesters such as polylactic 
acid involved the use of initiators, catalysts, and/or 
solvents which are usually toxic, and hence, these poly-
esters cannot be considered as completely biocompat-
ible (Orchel et al. 2013). On the other hand, catalyst-free 
polyesterification has recently become another attrac-
tive route to develop biocompatible thermoset polyes-
ters for soft tissue engineering applications (Barrett and 
Yousaf 2010). Polycondensation polymerization demon-
strates a simpler, cost-effective, smaller-scale synthe-
sis (requiring only a small amount of monomers) and 
does not require a complex experimental setup com-
pared to ring-opening polymerization or an enzymatic 
polymerization.
Thermoset polyesters can be synthesized by heating 
the monomers (polyol and polyacid) in normal atmosphere 
or partial vacuum, followed by a post curing procedure 
(durations vary depending on the type of monomers). The 
chances of the polyesters to induce a toxic response are 
minimized because no toxic catalyst or solvent is involved 
in the polymerization process. Also, the mechanical prop-
erties and degradation rates can be tailored by manipu-
lating the type of monomers, feed ratios, and curingconditions. Additionally, thermoset polyesters can be 
designed to be completely amorphous which can provide 
a more linear mechanical property loss with time and a 
more stable structure throughout the degradation process 
(Wang et al. 2003, Amsden 2007, Barrett and Yousaf 2010). 
In order to reduce the scope, this review will focus on bio-
degradable polyol-based polyesters synthesized by cata-
lyst- or solvent-free polycondensation.
2 Monomers
From a soft tissue engineering standpoint, biodegradable 
polyesters should be totally amorphous and can exhibit 
rubberlike elasticity, biocompatibility, tunable mechani-
cal properties, and degradation rates, have a glass tran-
sition temperature below human body temperature, and 
can be easily processed into various shapes (Amsden 
2007). Thermoset polyesters are capable of fulfilling these 
requirements by combining a wide range of polyol and 
polyacid monomers (Table  2). Monomers endogenous 
to human natural metabolism are selected to derive the 
polyesters to enhance the biocompatibility and minimize 
the toxic effects of the degradation products (Barrett and 
Yousaf 2009, 2010).
A broad range of mechanical properties and degrada-
tion rates can be covered by combining monomers with 
different chain lengths, by monomers stoichiometry, 
and by varying the curing conditions. Furthermore, the 
free alcohol groups after the reaction can be subjected 
to modification by biomolecules such as peptides (You 
et al. 2010). The unavoidable limitations of polyol-based 
biodegradable polyesters are the melting point and 
boiling point of the monomers. During synthesis, the 
monomer should be able to remain in liquid state where 
the reaction temperature is commonly between 100°C 
and 150°C. Some researchers used vacuum or nitrogen 
gas to remove the water vapor formed throughout the 
synthesis. Some of the monomers used in the synthesis 
of polyol-based biodegradable polyesters are discussed 
below.
2.1 Glycerol
Glycerol is a basic building block for lipids and has been 
approved for use in medical applications by the US Food 
and Drug Administration (FDA) (Rai et  al. 2012). The 
chemical structure of glycerol allows it to form three-
dimensional crosslink structures when reacting with 
diacid monomers.
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W.H. Tham et al.: Polyol-based biodegradable polyesters      3
Table 2: Types of polyols and their molecular structures.
Polyols   Molecular structure
Glycerol  
Erythritol  
Threitol  
Xylitol  
Sorbitol  
Mannitol  
Maltitol  
Dicarboxylic acid  
Citric acid  
α-Ketoglutaric acid 
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4      W.H. Tham et al.: Polyol-based biodegradable polyesters
2.2 Sugar alcohol
Erythritol, threitol, xylitol, sorbitol, mannitol, and maltitol 
are commonly used as sugar substitutes that are approved 
by FDA due to their low caloric content (Bernt et al. 1996, 
Edgar 1998, Lynch and Milgrom 2003). These monomers 
can be metabolized in an insulin-independent manner 
(Ellwood 1995, Natah et al. 1997).
2.3 Adipic, sebacic, and dodecanedioic acid
Adipic acid, sebacic acid, and dodecanedioic acid are the 
metabolic intermediates in ω-oxidation of medium- and 
long-chain fatty acids (Grego and Mingrone 1995, Liu et al. 
1996, Shet et  al. 1996) and have been shown to be non-
toxic in vivo (Tamada and Langer 1992). The polymers 
containing sebacic acid have been approved for medical 
applications (Rai et al. 2012).
2.4 Citric acid, succinic acid, and 
α-ketoglutaric acid
Citric acid, succinic acid, and α-ketoglutaric acid are 
Krebs cycle intermediates (Lowenstein 1967, Barrett and 
Yousaf 2009). Citric acid is also a natural preservative and 
has been widely used in the food industry as a flavoring 
agent. Succinic acid is widely used as an acidity regulator 
in the food and beverage industry.
2.5 Poly(glycerol sebacate)
Poly(glycerol sebacate) (PGS) is a novel biodegrad-
able polyester elastomer developed by Robert Langer’s 
groups in 2002 (Wang et al. 2002) and has been recently 
reviewed by Rai et  al. (2012). PGS elastomers demon-
strate attractive properties for soft tissue engineering 
applications. PGS has been investigated for myocar-
dial (Chen et  al. 2008, 2010, Engelmayr et  al. 2008, 
Radisic et al. 2008, Jean and Engelmayr 2010), vascular 
(Motlagh et al. 2006, Gao et al. 2007, Crapo et al. 2008, 
Crapo and Wang 2010), cartilage (Jeong and Hollister 
2010, Kemppainen and Hollister 2010), retinal (Neeley 
et al. 2008, Redenti et al. 2009, Pritchard et al. 2010a,b, 
Ghosh et al. 2011), and nerve tissue engineering (Sund-
back et  al. 2005) and also as a drug carrier (Sun et  al. 
2009a). This thermoset bioelastomer is synthesized by 
polycondensation between glycerol and sebacic acid. 
The degradation products of PGS are non-toxic as both 
glycerol and sebacic acid are natural metabolites (Grego 
and Mingrone 1995). The reaction yields an almost 
colorless elastomer, having a random crosslinked poly-
ester network and pendant hydroxyl groups attached 
to the backbone. Covalent crosslink networks give PGS 
an elastic characteristic and better mechanical proper-
ties, while the hydroxyl groups improve the mechanical 
strength by participating in hydrogen bonding interac-
tions. These pendant hydroxyl groups also make the 
surface of the PGS hydrophilic.
PGS showed both biocompatible in vitro and 
minimal inflammatory responses during subcutaneous 
implantation in vivo (Wang et al. 2002). Degradation of 
PGS was also compared with poly(lactide-co-glycolide) 
(PLGA). In vivo degradation studies found that PGS 
degraded through surface erosion (Wang et  al. 2003). 
Throughout the 35-day testing period, PGS samples lost 
weight steadily while maintaining their geometries and 
mechanical strength with only 15% of water content 
(Wang et  al. 2003). In contrast, the geometry of PLGA 
samples was distorted after 14 days. The surfaces of these 
PGS and PLGA samples were characterized by scanning 
electron microscopy after implantation. The surface of 
PGS maintained its integrity, while holes and crack for-
mation were observed on the PLGA samples. PGS was 
estimated to be fully degraded after 2  months in vitro. 
Recent research also found that a commonly used drug, 
5-fluorouracil (5-FU), can be chemically conjugated with 
PGS to form a biodegradable drug carrier. The in vitro 
drug release profiles of this drug-loaded PGS exhibited a 
biphasic release with an initial exponential phase in the 
first week followed by a constant linear phase. The in 
vivo degradation results showed that the release of 5-FU 
from the drug-loaded PGS lasted for a month (Sun et al. 
2011).
PGS is attractive in terms of its simple processing 
method. The prepolymer can be synthesized through 
heating a small amount of monomers (~100 g) without 
any harsh solvent or catalysts. Although PGS elastomer 
is a thermoset, the uncrosslinked prepolymer can be pro-
cessed into various geometries by melting into liquid or 
dissolving in common organic solvents such as 1,3-diox-
olane, tetrahydrofuran, ethanol, isopropanol, and N,N-
dimethylformamide. Crosslinked PGS exhibits a Young’s 
modulus of 0.282  MPa with an ultimate tensile strength 
(UTS)  > 0.5  MPa and strain to failure  > 267%. Another 
advantage of PGS elastomers is that their mechanical and 
degradation properties can be tailored by manipulating 
the curing temperature, time, and molar ratio of the mon-
omers. By varying these conditions such as increasing the 
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W.H. Tham etal.: Polyol-based biodegradable polyesters      5
curing duration (Pomerantseva et al. 2009), the crosslink 
density increased and the Young’s modulus of PGS elas-
tomers rose from 0.28 to 1.50  MPa and UTS 0.28–0.70 
MPa, but the strain to failure was reduced from 160% to 
125%. PGS also has shown an excellent shape memory 
effect with a recovery ratio of above 99.5% (Cai and Liu 
2008). When the deformed samples were cooled to -40°C, 
the shapes of the samples in deformed shape were very 
stable. The samples can return to initial shape in around 
20 s after raising the temperature to 37°C.
Liu et  al. (2005, 2007a,b) reported a class of ther-
moplastic PGS (TMPGS) elastomers (sol contents  > 60%) 
synthesized from a two-step method. Basically, the 
prepolymer-synthesizing step remained the same, but 
the prepolymer was cured using hot-pressed technique. 
TMPGS elastomers with different molar ratio (glycerol/
sebacic acid: 2/2.5, 2/3, 2/3.5, and 2/4) were investigated, 
and the elastomers can be hot-pressed into various 
shapes. As the amount of sebacic acid in the polymer 
increased, the Young’s modulus improved from 0.0725 
to 7.052 MPa, but the elongation at break decreased from 
114% to 12%. In vitro degradation studies for TMPGS indi-
cated that the mass losses of the samples were 10–15% 
after 1 day of degradation. However, the hydrolytic mech-
anism of the samples involving both bulk and surface 
degradation resulted in poor dimension stability during 
degradation limiting their application in biomedicines 
(Liu et al. 2009).
2.6 Poly(glycerol sebacate citrate)
Poly(glycerol sebacate citrate) (PGSC) was developed by Liu 
et al. (2009) with the purpose of improving the mechanical 
properties of PGS through incorporating citric acid. At the 
same time, the curing duration of pure PGS was reduced. 
PGSC prepolymers were prepared in two steps: first, an 
equimolar mixture of glycerol and sebacic acid was heated 
at 130°C under 1 kPa for 20  h to obtain the prepolymer, 
then a predetermined amount of citric acid was added 
into the PGS prepolymer followed by heating at 120°C 
for 1  h to obtain the moldable mixtures. These mixtures 
were cured at 120°C for 8 h–18 h to obtain a group of elas-
tomers with different properties. The findings suggested 
that as the concentration of citric acid increases, elasto-
mers will have higher crosslinking density and increased 
hydrogen bonding actions, and hence, the mechanical 
strengths were improved. Cured PGSC can be obtained 
in shorter curing duration (~8 h) compared to pure PGS 
which required more than 1 day (Wang et al. 2002). PGSC 
elastomers showed Young’s modulus, tensile strength, 
and elongation at break range from 0.61 to 3.26 MPa, 
0.63–1.46 MPa, and 51%–170%, respectively. PGSC elasto-
mers were hydrophilic, and in vitro degradation studies 
showed that the mass loss of the elastomers was  < 20% 
after 28 days of testing. The samples preserved the dimen-
sion stability throughout the degradation studies.
2.7 Poly(glycerol sebacate lactic acid)
Sun et  al. (2008, 2009b) investigated on modifying the 
degradation characteristics of PGS by doping lactic acid, 
which has both hydroxyl and carboxyl groups, into the 
backbone of PGS polymer. A series of poly(glycerol seba-
cate lactic acid) (PGSL) was synthesized by reacting glyc-
erol, sebacic acid, and lactic acid (ratio:1/1/0, 1/1/0.25, 
1/1/0.5 and 1/1/1) at 150°C for 6 h followed by postpolym-
erization at 140°C for 30  h under vacuum (40 mTorr). 
Degradation studies on PGSL samples showed that the 
mass losses of all the samples are  < 25% after immersion 
for 80  days in phosphate buffered saline (PBS) solution 
except for PGSL (1/1/0.25) which is around 42% of mass 
loss. As the concentration of lactic acid increased, the ester 
groups formed in the polymer backbone increased, and 
therefore a longer degradation time is required to cleave 
these ester bonds. The morphology of PGSL during degra-
dation studies was investigated, and it was found that the 
samples degraded through both surface erosion and bulk 
degradation. Initially, PGSL samples maintained their 
structure during the degradation process. However, after 
30 days of study, minor crack formation was observed on 
the surface of the elastomers. The elastic modulus of PGSL 
elastomers increased from 6.5 to 21 MPa with increasing 
concentration of lactic acid. PGSL elastomers were then 
investigated as surgical sealants by Chen et al. (2011) with 
a slight modification in the synthesis procedures. Sealants 
prepared from PGSL demonstrated a significantly higher 
adhesive strength than either fibrin sealants of synthetic 
PleuraSealTM. Also, the sealants can be applied easily at 
45°C, which subsequently solidified into a soft wax-like 
patch at body temperature. In vitro cytocompatibility tests 
using mouse STO-Neo-LIF (SNL) fibroblast cells showed 
that the addition of lactic acid into PGS significantly 
improved the cytocompatibility of PGSL compared with 
the pure PGS.
2.8 Poly(glycerol dodecanedioate)
A novel biodegradable polyester elastomer with a glass 
transition temperature (Tg) of ~32°C was described by 
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6      W.H. Tham et al.: Polyol-based biodegradable polyesters
Migneco et  al. (2009). This elastomer was synthesized 
from glycerol and dodecanedioic acid and is also known 
as poly(glycerol dodecanedioate) (PGD). Dodecanedioic 
acid, an intermediate from ω-oxidation of lauric acid, was 
chosen as difunctional acid because it can be metabo-
lized in human metabolism (Grego and Mingrone 1995, 
Liu et al. 1996). The attractive characteristic of PGD is that 
it can change from a stiff material at room temperature 
into a soft and elastic material at body temperature. The 
synthesis of PGD elastomer was carried out by mixing the 
monomers for 24 h at 120°C under atmospheric pressure 
followed by further reaction in vacuum for another 24 h 
to prepare the prepolymer. Cured PGD was obtained after 
curing the prepolymer under vacuum at 90°C for 48  h. 
Mechanical properties of PGD showed a drastic change 
when the temperature was elevated. The Young’s modulus 
at 21°C and 37°C are 136.55  MPa and 1.08 MPa, respec-
tively. The strain at break of PGD at 21°C is 225% and 123% 
at 37°C. After PGD elastomer was elongated to 60, 80, and 
100%, the elastomer returned to its original length when 
heated to 32°C, indicating that PGD has shape memory 
features. The degradation rate of PGD is relatively slower 
compared to those of PGS and POC. PGD retained 87.4% of 
its total mass after 90 days of soaking in PBS solution at 
37°C. PGD also showed acceptable in vitro biocompatibil-
ity. PGD was able to be electrospun into fibrous scaffolds 
where the diameters of these fibers could be adjusted by 
manipulating the concentration of PGD (Dai and Huang 
2014, Dai et  al. 2014). The in vitro biocompatibility test 
results showed that cells derived from mouse embryonic 
stem cells could adhere to and grow on the PGD scaffolds. 
The cell adhesion and proliferation of this fibrous scaffold 
could be enhanced by blending PGD with gelatin.
2.9 Poly(1,3-diamino-2-hydroxypropane 
polyol sebacate)
A new class of biodegradable thermoset elastomers, 
termed poly(1,3-diamino-2-hydroxypropane polyol seba-
cate) (PAPS), synthesized from condensation polym-
erization of sebacic acid, 1,3-diamino-2-hydroxypropane 
(DAHP), and either glycerol or D,L-threitol, was intro-
duced by Bettinger et al. (2008, 2009). DHAP was chosen 
as monomer because it is non-toxic (Roy et al. 2005), mul-
tifunctionally enables the formation of crosslink network, 
contains primary amines which participate in hydrogen 
bonding, and has the ability to form both amide and ester 
bonds for the purposeof altering the properties of the 
elastomers. Generally, the prepolymers were synthesized 
by heating sebacic acid, DAHP, and glycerol/D,L-threitol 
at 120°C for 3 h under a nitrogen blanket. The reaction was 
continued for another 9 h under vacuum. PAPS elastomers 
were obtained after curing the prepolymers at 170°C under 
vacuum for 24 h or 48 h. The elastomers achieved Young’s 
modulus, UTS, and rupture strain ranging from 1.45 to 
4.34 MPa, 0.24–1.69 MPa, and 21%–92%, respectively. The 
degradation of PAPS elastomers in vitro was studied in the 
presence of sodium acetate buffer for 6 weeks. The elas-
tomers experienced mass loss ranging from 42.8 to 97%. 
PAPS elastomers also showed biocompatibility both in 
vitro and in vivo, with projected degradation half-lives up 
to 20 months in vivo.
2.10 Xylitol-based elastomers
The selection of suitable monomers is one of the critical 
tasks in developing biodegradable elastomers for poten-
tial use in biomedical applications. Xylitol, a multifunc-
tional monomer which is non-toxic and endogenous to the 
human metabolic system, is an excellent candidate in the 
synthesis of biodegradable elastomers. Bruggeman et al. 
(2008a, 2010) successfully synthesized xylitol-based elas-
tomers via polycondensation between xylitol and citric 
acid, poly(xylitol citrate) (PXC), and between xylitol and 
sebacic acid, poly(xylitol sebacate) (PXS). The synthesis 
of PXC and PXS prepolymers were carried out at 150°C 
for 2  h followed by reaction under vacuum (50  mTorr). 
PXC is a biodegradable and water-soluble prepolymer. 
In order to crosslink PXC prepolymer, acrylation was 
carried out using methacrylic anhydride. Photopolymeri-
zation of the resulting polymer yielded PXC-methacrylate 
(PXCma) hydrogel. On the other hand, PXS elastomers 
were obtained after post-polymerization at 120°C under 
vacuum for 4 days. PXS showed characteristics similar to 
those of PGS and POC elastomers which are tough, elastic, 
biodegradable, and tunable mechanical and degradation 
properties.
By changing the initial monomer ratio of sebacic 
acid, PXS with a range of properties can be obtained 
while maintaining the elastic properties. For example, 
the Young’s modulus of PXS 1:2 (xylitol/sebacic acid) 
was up to 5.3  MPa with an elongation at break of 33%; 
the Young’s modulus PXS 1:1 was lower (0.8 MPa), but it 
was more elastic (205% elongation at break). However, 
as the concentration of sebacic acid increased, the elas-
tomers became less hydrophilic and harder to degrade. 
The in vitro degradation results showed that PXS 1:1 was 
fully degraded after 7 weeks but PXS 1:2 lost only 13% of 
its mass after 25 weeks. The elastomers were degraded via 
surface erosion, and their structural integrity was highly 
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W.H. Tham et al.: Polyol-based biodegradable polyesters      7
maintained during the degradation process. Xylitol-based 
elastomers also exhibited excellent biocompatibility both 
in vitro and in vivo (Bruggeman et al. 2010).
A family of polyesters, poly(xylitol dicarboxylates) 
(PXD), synthesized from xylitol with different diacids 
(succinic acid, adipic acid, suberic acid, or sebacic acid) 
by melt condensation, was reported by Dasgupta et  al. 
(2014), who proposed a combinatorial approach where 
three independent parameters, namely, the chain length 
of the diacid, stoichiometric ratios, and curing durations, 
were varied to tailor the properties (degradation rates, 
mechanical properties, and release kinetics) of PXD poly-
esters. PXD prepolymers were synthesized at 150–180°C 
for 2  h followed by another 14–24  h under vacuum to 
increase the prepolymer yield. Then, the postpolymeri-
zation step was carried out at 120°C under vacuum for 
3–14  days to obtain the cured PXD polyesters. It can be 
summarized that an increase in the diacid chain length, 
diacid feed mole ratio, or curing duration will increase 
the degree of crosslinking and storage modulus of the 
polyesters, whereas the degradation rate and dye release 
rate decrease. Moreover, by manipulating these para-
meters, PXD polyesters with similar mechanical proper-
ties but different degradation rates or vice versa can be 
developed. These findings showed that PXD polyesters 
are a more versatile class of polymers compared to tradi-
tional polymers.
2.11 Poly(polyol sebacate)
The combination of xylitol and sebacic acid yielded an 
elastomer with very good properties (Bruggeman et  al. 
2008a). Hence, a family of novel biodegradable polyes-
ter elastomers, designated poly(polyol sebacate) (PPS), 
which were composed of various types of polyols, were 
also investigated by Bruggeman et al. (2008b). Four types 
of polyols were selected to form biodegradable polyesters, 
which include xylitol, sorbitol, mannitol, and maltitol. 
Generally, the mechanical properties and degradation 
rates of PPS elastomers were affected by the choice of 
polyol monomer and the molar ratio of sebacic acid. Poly-
condensation between polyols and sebacic acid yielded 
PXS, poly(sorbitol sebacate) (PSS), poly(mannitol seba-
cate) (PMS), and poly(maltitol sebacate) (PMtS). The pre-
polymers were prepared by heating monomers at 150°C 
for 2 h under atmospheric pressure, and these reactions 
were continued for another 2–12  h under vacuum. PPS 
elastomers were obtained after curing the prepolymers 
at 120–150°C for 4 days under vacuum. These elastomers 
achieved Young’s modulus ranging from 0.37 to 378 MPa, 
UTS between 0.61 and 17.64 MPa, and ultimate elongation 
between 11 and 205%.
Among the PPS elastomers, the formulation PSS 1:1 
(sorbitol/sebacic acid) was the softest and most hydro-
philic elastomer with a Young’s modulus, ultimate elon-
gation, and contact angle of 0.37 MPa, 192%, and 9.6°, 
respectively. By increasing the concentration of sebacic 
acid, the Young’s modulus of PPS 1:2 was improved to 
2.67 MPa; however, the ultimate elongation decreased to 
65%. PMtS 1:4 on the other hand was the stiffest elasto-
mer with a Young’s modulus of 378 MPa with only 10.9% 
ultimate elongation. The rates of degradation of the elas-
tomers were also affected by the type of polyols and the 
concentration of sebacic acid. All the PPS elastomers 
were degraded in PBS at 37°C for 3 months. PSS 1:1 and 
PMS 1:1 showed the greatest mass loss of 15% and 21%, 
respectively. On the other hand, PMts 1:4 degraded  < 1% 
of its original mass. PSS 1:1 and PSS 1:2 elastomers showed 
acceptable biocompatibility both in vitro and in vivo, and 
surprisingly, PPS 1:1 was completely degraded after 12 
weeks during an in vivo biocompatibility study. Recently, 
Ning et  al. (2011) developed a synthetic method for an 
effective preparation of PPS elastomers (PXS, PSS, and 
PMS). Water formed during the polycondensation reaction 
was removed by high flow rate of nitrogen gas rather than 
using high vacuum. Typically, PPS prepolymers were pre-
pared from the reaction of polyols with sebacic acid under 
high flow rate of nitrogen gas (0.1 m3/h) at 160°C. The post-
polymerization was carried out at 140°C up to 200°C with 
different curing duration.
2.12 Sorbitol- and mannitol-based 
polyesters
Pasupuleti and Madras (2011) synthesized two new 
classes of polyester elastomers from the combination of 
sorbitol with citric, tartaric, and sebacic acids, designated 
as poly(sorbitol citric sebacate) (PSCS) and poly(sorbitol 
tartaric sebacate) (PSTS). All of these monomers can be 
metabolized in the human body: sorbitol can be com-
pletely metabolized to carbon dioxide (Adcock and Gray 
1956, Sestoft 1985); sebacic acid is an intermediate in fatty 
acid oxidation (Mortensen 1981); citric acid can be metab-
olized in the Krebs cycle (Krebs and Johnson 1980); and 
tartaric acid is a natural product(Yokoe et al. 2005). PSCS 
and PSTS were synthesized using simple procedures. The 
monomers were mixed and reacted at 150°C for 2 h under 
atmospheric pressure without catalysts to get the prepoly-
mers. Then, these prepolymers were post-polymerized in 
an oven at 80°C for 5 days to prepare the elastomers.
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8      W.H. Tham et al.: Polyol-based biodegradable polyesters
Elastomers with a wide range of mechanical prop-
erties were obtained by varying the feed mole ratio 
of the monomers. The Young’s modulus ranged from 
1.06 to 462.65 MPa, tensile strength ranged from 0.45 to 
20.32 MPa, and elongation at break ranged from 20% to 
578%. In vitro degradation studies showed that the half-
life of these elastomers ranged from 0.54 to 38.52 days. The 
degradation rates become more rapid with increased citric 
acid or tartaric acid concentration due to the release of 
more carboxyl groups, which autocatalyzed the hydrolytic 
reaction (Yao et  al. 2003). The mechanical properties of 
PSCS were higher than PSTS, while the degradation rates 
of PSCS were lower than PSTS at any given composition 
due to the structural difference between citric and tartaric 
acids, which give different degrees of crosslinking.
A family of novel polyesters, poly(mannitol citric 
dicarboxylate) (PMCD) (Table  3), were also developed 
from mannitol, citric acid, succinic acid, adipic acid, 
and sebacic acid (Pasupuleti et  al. 2011). The result-
ing polyesters were named as poly(mannitol citric suc-
cinate) (PMCSu), poly(mannitol citric adipate) (PMCA), 
and poly(mannitol citric sebacate) (PMCS). The Young’s 
modulus of these polyesters varied from 12.25 to 660 MPa 
and elongation at break ranged from 14.2% to 180.7%. 
The degradation rates of the polyesters are in the follow-
ing order: PMCSu > PMCA > PMCS. PMSCs were degraded 
more than 50% from its original mass after being incu-
bated for 4 days in PBS solutions, while both PMCA and 
PMCSu were fully degraded within a day in a PBS envi-
ronment. The polyesters demonstrated versatile drug 
delivery characteristics after testing with organic dyes 
(rhodamine B and orange G).
2.13 Castor oil-based and ricinoleic acid-
based poly(mannitol citric sebacate)
A family of castor oil-based PMCS (CoPMCS) was syn-
thesized by introducing castor oil, a hydrophobic and 
biocompatible monomer, into PMCS polyesters with the 
target of developing a soft and flexible elastomer (Sathis-
kumar and Madras 2011, Sathiskumar et  al. 2012). The 
Young’s modulus of CoPMCSs ranged from 0.97 to 3.93 
MPa, and the elongation at break ranged from 38% to 
67%. CPMCS polyesters degraded by bulk erosion, and 
most of the polyesters were fully degraded within 21 days. 
All CoPMCSs polyesters were found to be non-cytotoxic 
after being studied using human foreskin fibroblast cell. 
CoPMCS loaded with 5-FU showed that the drug release 
has a biphasic nature, while polyesters with isoniazid 
showed a controlled release profile for a period of 16 days.
Chandorkar et al. (2013) prepared a family of ricinoleic 
acid-based polyesters (RPMCS) from polycondensation 
of ricinoleic, sebacic, citric acids, and mannitol. Ricin-
oleic acid is the only naturally occurring fatty acid with 
a hydroxyl and an acid group in the structure (Jain et al. 
2008). It is known to exhibit a combination of an analge-
sic and an anti-inflammatory effect when administered 
topically (Vieira et al. 2000). RPMCS exhibited a range of 
elastic modulus and rupture strain from 22 MPa to 80 MPa 
and 37%–82%, respectively. In vitro degradation in PBS 
showed that the polyesters were degraded completely 
within 300 h with a first-order reaction kinetics. The bio-
compatibility of RPMCS tested with mouse myoblast cells 
revealed good cell attachment and growth.
2.14 Salicylic acid-based poly(mannitol 
sebacate)
With the aim of developing biodegradable polymers which 
support sustained release of salicylic acid, Chandorkar et al. 
(2014) successfully developed PMS polyester with salicylic 
acid incorporated in the polymeric backbone also know as 
salicylic acid-based polyester (SAP). Salicylic acid and its 
derivatives are commonly used as low-cost drugs (Rosen-
berg et al. 2008). The benefits of salicylic acid include the 
following: it may reduce risk of colorectal cancer (Bastiaan-
net et al. 2012), it can be used as antibacterial agent and 
antibiofilm-forming agent (Price et al. 2000), and it can be 
used as an antifungal agent (Amborabé et al. 2002). Briefly, 
SAP prepolymer was prepared (diacid (COOH) groups/
mannitol (OH) groups ratio 0.66) by high vacuum at 180°C 
until its viscosity increased followed by postcuring at 130°C 
under vacuum for 24  h to obtain the cured SAP. SAP is a 
hydrophobic polyester with a contact angle of 102.7°. SAP 
polyester was degraded via surface erosion where the mass 
loss of the polyester was around 24% in 4 months during 
in vitro degradation studies. SAP polyester exhibited a sus-
tained release rate, with 3.5% salicylic acid being released 
in 4 months. The cytocompatibility of SAP polyester was 
evaluated using C2C12 murine myoblast cells. It was found 
that SAP promotes cell proliferation and the cells adhere 
to the surface of the material. Although salicylic acid was 
released to the culture medium, no excess cell death as 
compared to control was observed.
2.15 Poly(triol α-ketoglutarate)
A family of novel biodegradable elastomers, poly(triol 
α-ketoglutarate) (PTK), was reported by Barrett and 
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W.H. Tham et al.: Polyol-based biodegradable polyesters      9
Ta
bl
e 3
: 
Ch
em
ica
l s
tru
ct
ur
e o
f p
ol
yo
l-b
as
ed
 b
io
de
gr
ad
ab
le
 p
ol
ye
st
er
s.
Po
ly
es
te
r
 
St
ru
ct
ur
e
 
Re
fe
re
nc
es
Po
ly
(g
ly
ce
ro
l s
eb
ac
at
e)
, P
GS
 
 
W
an
g 
et
 al
. (
20
02
)
Po
ly
(g
ly
ce
ro
l s
eb
ac
at
e c
itr
at
e)
, P
GS
C
 
 
Liu
 et
 al
. (
20
09
)
Po
ly
(g
ly
ce
ro
l s
eb
ac
at
e l
ac
tic
 a
cid
), 
PG
SL
 
 
Su
n 
et
 al
. (
20
08
)
Po
ly
(g
ly
ce
ro
l d
od
ec
an
ed
io
at
e)
, P
GD
 
 
M
ig
ne
co
 et
 al
. (
20
09
)
Po
ly
(1
,3
-d
ia
m
in
o-
2-
hy
dr
ox
yp
ro
pa
ne
 
po
ly
ol
 se
ba
ca
te
), 
PA
PS
 
 
Be
tti
ng
er
 et
 al
. (
20
08
)
Po
ly
(x
yl
ito
l s
eb
ac
at
e c
itr
at
e)
-
m
et
ha
cr
yla
te
, P
XC
m
a
 
 
Br
ug
ge
m
an
 et
 al
. (
20
08
a)
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10      W.H. Tham et al.: Polyol-based biodegradable polyesters
Po
ly
es
te
r
 
St
ru
ct
ur
e
 
Re
fe
re
nc
es
Po
ly
(p
ol
yo
l s
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ac
at
e)
, P
PS
 
i. 
Po
ly
(x
yl
ito
l s
eb
ac
at
e)
, P
XS
 
ii.
 P
ol
y(
so
rb
ito
l s
eb
ac
at
e)
, P
SS
 
iii
. P
ol
y(
m
an
ni
to
l s
eb
ac
at
e)
, P
M
S
 
iv.
 P
ol
y(
m
al
tit
ol
 se
ba
ca
te
), 
PM
tS
 
 
Br
ug
ge
m
an
 et
 al
. (
20
08
b)
Po
ly
(s
or
bi
to
l c
itr
ic 
se
ba
ca
te
), 
PS
CS
 
 
Pa
su
pu
le
ti 
an
d 
M
ad
ra
s (
20
11
)
Ta
bl
e 3
 (
co
nt
in
ue
d)
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W.H. Tham et al.: Polyol-based biodegradable polyesters      11
Po
ly
es
te
r
 
St
ru
ct
ur
e
 
Re
fe
re
nc
es
Po
ly
(s
or
bi
to
l t
ar
ta
ric
 se
ba
ca
te
), 
PS
TS
 
 
Pa
su
pu
le
ti 
an
d 
M
ad
ra
s (
20
11
)
Po
ly
(m
an
ni
to
l c
itr
ic 
di
ca
rb
ox
yla
te
), 
PM
CD
 
 
Pa
su
pu
le
ti 
et
 al
. (
20
11
)
Ca
st
or
 o
il-
ba
se
d 
po
ly
(m
an
ni
to
l c
itr
ic 
se
ba
ca
te
), 
Co
PM
CS
 
 
Sa
th
is
ku
m
ar
 a
nd
 M
ad
ra
s (
20
11
)
Ri
cin
ol
ei
c a
cid
-b
as
ed
 p
ol
y(
m
an
ni
to
l 
cit
ric
 se
ba
ca
te
), 
RP
M
CS
 
 
Ch
an
do
rk
ar
 et
 al
. (
20
13
)
Sa
lic
yl
ic 
ac
id
-b
as
ed
 p
ol
y(
m
an
ni
to
l 
se
ba
ca
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)
 
 
Ch
an
do
rk
ar
 et
 al
. (
20
14
)
Ta
bl
e 3
 (
co
nt
in
ue
d)
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12      W.H. Tham et al.: Polyol-based biodegradable polyesters
Po
ly
es
te
r
 
St
ru
ct
ur
e
 
Re
fe
re
nc
es
Po
ly
(tr
io
l α
-k
et
og
lu
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), 
PT
K
 
 
Ba
rre
tt 
an
d 
Yo
us
af
 (2
00
8)
Po
ly
(e
ry
th
rit
ol
 d
ica
rb
ox
yla
te
), 
PE
rD
 
 
Ba
rre
tt 
et
 al
. (
20
10
a)
Po
ly
(s
or
bi
to
l i
ta
co
na
te
-co
-s
or
bi
to
l 
su
cc
in
at
e)
, P
SI
-co
-S
S
 
 
Ba
rre
tt 
et
 al
. (
20
10
b)
Po
ly
(s
or
bi
to
l s
eb
ac
at
e m
al
at
e)
, P
SS
M
 
 
Th
am
 et
 al
. (
20
12
)
Po
ly
(x
yl
ito
l d
od
ec
an
ed
io
at
e)
, P
XD
D
 
 
W
on
g 
et
 al
. (
20
14
)
 
*R
 = h
yd
ro
ge
n 
(H
) o
r p
ol
ym
er
 
Ta
bl
e 3
 (
co
nt
in
ue
d)
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W.H. Tham et al.: Polyol-based biodegradable polyesters      13
Yousaf (2008). PTK elastomers contained ketones in the 
polymers backbone formed by condensation polymeriza-
tion of α-ketoglutaric acid with one of three triols (glycerol, 
1,2,4-butanetriol, and 1,2,6-hexanetriol). The synthesis of 
prepolymers was carried out at 125°C for 1 h. Then, these 
prepolymers were precipitated in -78°C methanol and 
concentrated by rotary evaporation followed by drying 
under vacuum at room temperature. PTK elastomers were 
obtained after curing the prepolymers at 60–120°C for 
6  h–7 days. Through changing the curing temperature, 
duration, and also the types of triols, PTK elastomers with 
a range of mechanical properties and degradation rates 
can be obtained. The Young’s modulus of various PTKs 
ranged from 0.1 to 657.4 MPa, ultimate stress between 
0.2 and 30.8 MPa, and ultimate strain from 22% to 583%, 
which are similar to several types of natural tissues such 
as bovine ligament, collagen, arteries, and veins (Barrett 
and Yousaf 2008). PTKs synthesized under different condi-
tions showed complete mass loss as fast as 2 days, and the 
slowest took 28 days during degradation in PBS solution 
at 37°C. Generally, all PTKs are non-toxic after evaluating 
using mouse fibroblast because the monomers are natu-
rally occurring metabolites. However, the surfaces of PTKs 
required modification with peptide ligands for better cell 
attachment and proliferation. Therefore, a solution of bio-
specific cell-adhesive peptides, glycine-arginine-glycine-
aspartic acid-serine (H2NO-GRGDS), was added directly 
on the top of the elastomer films and reacted for 5 h with 
the purpose of functionalizing the elastomers surface.
2.16 Poly(erythritol dicarboxylate)
The previously described PTK exhibited a range of mechan-
ical properties that covered several types of natural 
tissues. However, the rapid degradation rates (2–28 days) 
of PTK elastomers limited their application in soft tissue 
engineering. Hence, another family of novel biodegrad-
able polyester elastomers, poly(erythritol dicarboxylate) 
(PErD), was prepared by Barrett et al. (2010a). Erythritol is 
a human consumable sugar alcohol approved by the FDA. 
Erythritol was reacted with 5- to 10-, 12-, and 14-carbon 
dicarboxylic acids to form poly(erythritol glutarate) 
(PErG), poly(erythritol adipate) (PErGl), poly(erythritol 
pimelate) (PErPi), poly(erythritol suberate) (PErSu), 
poly(erythritol azelate) (PErAz), poly(erythritol sebacate) 
(PErSe), poly(erythritol dodecanedioate) (PErDo), and 
poly(erythritol tetradecanedioate) (PErTe), respectively. 
The polycondensation reaction was at 145°C for 2 h, con-
tinued by further reaction for 7 h under vacuum (2 Torr). 
The prepolymers were then cooled to room temperature, 
dissolved in a minimal amount of tetrahydrofuran, puri-
fied by precipitation in -78°C methanol, and dried by 
rotary evaporation. The elastomers were prepared by 
curing these prepolymers at 120°C for 3 days or 140°C for 
4 days. Polymerization of erythritol with various dicarbo-
xylic acids yield elastomers with ultimate tensile stress 
ranging from 0.14 to 16.65 MPa, Young’s modulus values of 
0.08–80.37 MPa, and rupture strain of 22%–466%. Most of 
the PErD elastomers returned to their original dimension 
after elongation except for PErDo and PErTe. Both PErDo 
and PErTe must be heated above their glass transition 
temperature in order to recover its original shape. PErDs 
elastomers with longer carbon chains showed lower deg-
radation rates due to the presence of more hydrophobic 
methylene groups in the matrix. PErDs degrade slower 
compared to PTKs. Degradation of PErDs in PBS solutions 
at 37°C showed that the rates of degradation of PErDs 
ranged from 100% mass loss in 3 weeks to 6.4% mass loss 
in 6 weeks. PErDs was non-cytotoxic after testing with 
Swiss albino 3T3 fibroblasts (SAFs) and human mesen-
chymal stem cells. Additionally, PErDs elastomers can be 
fabricated into micro-patterned polyester films, indicating 
the ease of processing.
2.17 Poly(sorbitol itaconate-co-sorbitol 
succinate)
Poly(sorbitol itaconate-co-sorbitol succinate) (PSI-co-SS) 
is a photocurable biodegradable polyester prepared from 
thermal polyesterification of itaconic acid, succinic acid, 
and sorbitol (Barrett et al. 2010b). Itaconic acid is a bio-
compatible monomer with a carbon double bond (C = C) 
that can be used for photocrosslinking reaction. The 
polyester exhibited a Young’s modulus, UTS, and rupture 
strain of 11.22 MPa, 2.05 MPa, and 119%, respectively. As 
sorbitol contains six hydroxyl groups, the polyester is 
very hydrophilic with a contact angle of 29.4°. Thus, in 
hydrated state, the Young’s modulus, UTS, and rupture 
strain of the polyester changed to 0.88 MPa, 0.11 MPa, and 
23%, respectively. The in vitro cytotoxicity test using SAFs 
showed that the polyester displayed moderate toxicity 
due to its high sol content (47.6%) that caused the culture 
medium to become acidic.
2.18 Poly(sorbitol sebacate malate) and 
poly(xylitol dodecanedioate)
Two novel biodegradable polyesters synthesized from 
polyol monomers were studied by the author’s research 
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14      W.H. Tham et al.: Polyol-based biodegradable polyesters
group. Poly(sorbitol sebacate malate) (PSSM) was synthe-
sized from sorbitol, sebacic acid, and malic acid (Tham 
et al. 2012). Both sorbitol and sebacic acid are biocompat-
ible as previously discussed, whilemalic acid had been 
investigated as a biodegradable polymer for drug delivery 
applications (Ding et al. 2011, Lanz-Landázuri et al. 2014). 
The polyesters exhibited a Young’s modulus, tensile 
strength, and elongation at break of 626.96 MPa, 16.2 MPa, 
and 49%, respectively. Next, poly(xylitol dodecanedioate) 
(PXDD) is another novel biodegradable polymer inves-
tigated by the author’s group (Wong et al. 2014). Both of 
these polyesters were mixed with hydroxyapatite (HA) to 
form composites. Surprisingly, a shape-memory behavior 
was detected after PXDD polyesters was incorporated with 
HA. The shape-memory property occurred at the tempera-
ture of 48°C, which is near to human temperature. This 
showed that PXDD composites have a good potential in 
clinical applications. On the other hand, PSSM/HA com-
posites demonstrated a significant improvement in the 
mechanical properties.
3 Scaffold fabrication techniques
The main purpose of designing novel biodegradable pol-
yol-based polyesters is to develop biomaterials for soft 
tissue engineering. These biomaterials must be developed 
as highly porous scaffolds to combine with cells from the 
body, which act as templates for tissue regeneration and 
to guide the growth of new tissue (O’Brien 2011). This 
section briefly discusses several techniques that are used 
to prepare scaffolds from polyol-based polyesters.
3.1 Salt leaching
Salt leaching technique is the most commonly used tech-
nique to develop three-dimensional scaffolds from pol-
yol-based polyesters. Unlike thermoplastic, polyol-based 
polyester scaffolds must be prepared during the prepoly-
mer stage. The prepolymer is dissolved in organic solvent 
such as tetrahydrofuran, 1,4-dioxane, or acetone to form 
a 20–25 wt% solution, followed by addition of sieved salt 
which acts as a porogen. The mixture is then cast into a 
mold. After the solvent evaporates, the mold is transferred 
into an oven for postcuring. The cured polyester is then 
immersed in distilled water until the salt was leached out 
followed by drying process. Porous scaffolds in flat and 
tubular shapes prepared from PGS polyester were investi-
gated by Gao et al. (2006). These scaffolds were found to 
support adhesion and proliferation of fibroblasts within 
the porous structure and form three-dimensional tissue 
engineered constructs within 8 days. Porous scaffolds 
were also successfully fabricated from PSCS, PSTS (Pasu-
puleti and Madras 2011), and PErD (Barrett et al. 2010a) 
polyesters.
The advantages of this technique are as follows: 
simple, small quantity of polymers required to prepare the 
scaffolds; high degree of porosity (typically up to 90%); 
controllable pore size (depending on the porogen size); 
and random interconnected pore structure (Joerg et  al. 
2005, Kramschuster and Turng 2013), which are important 
for cell seeding, migration, growth, mass transport, gene 
expression, and new tissue formation in three dimensions 
(Ma and Choi 2001, Choi et al. 2009). However, the limi-
tations of this method are that organic solvent residues 
might remain in the matrix (Liao et  al. 2012), the thick-
ness of the scaffold is limited, and the leaching step is 
time consuming. Also, this method is not suitable for 
fast-degrading polyesters discussed previously such as 
PMSC (Pasupuleti et al. 2011), CoPMSC (Sathiskumar and 
Madras 2011), RPMSC (Chandorkar et al. 2013), and PTK 
(Barrett and Yousaf 2008) due to the long exposure to 
aqueous medium in the leaching step.
3.2 Electrospinning
Electrospinning is a convenient method for the fabrica-
tion of ultrafine fiber including microfibers ( > 1 mm) or 
nanofibers ( < 1000 nm) from synthetic polymers and 
natural proteins (Matthews et  al. 2002, Casasola et  al. 
2014). The major components in electrospinning setup are 
high voltage power supply, syringe, spinneret (conductive 
needle connected to syringe), syringe pump, and collec-
tor. General electrospinning procedures are described 
below (Kumar et  al. 2013, Vivekanandhan et  al. 2014). 
Briefly, electrospinning solution is prepared dissolving 
the polymer with organic solvent. Then, the solution is 
transferred into a syringe that is installed to the syringe 
pump. The active lead of high voltage power supply is con-
nected to the electrospinning solution, and the grounding 
lead is attached to the collector. A high voltage is applied 
to the polymer solution, which overcomes the surface 
tension to form a charge jet. Electrostatic repulsion occur-
ring in the charged jet causes the jet to whip around, grad-
ually eliminating solvent from the fibers via evaporation. 
The continuous thin fiber (after solvent evaporation) is 
deposited on the grounded collector where the fiber accu-
mulates as non-woven randomly or uniaxially aligned 
sheets or arrays. The advantages of electrospun fibers 
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W.H. Tham et al.: Polyol-based biodegradable polyesters      15
include fiber diameters in the range of natural extracel-
lular matrix (ECM) (Furth and Atala 2014), high surface 
area to volume ratio, and that nanofibrous scaffolds fab-
ricated from electrospinning enhance cell attachment, 
proliferation, and differentiation (Smith et al. 2009). Also, 
a variety of natural materials (Sell et al. 2010) and thermo-
plastic polymers such as poly(lactic acid) (Casasola et al. 
2014), PLGA (Yu et al. 2014), and polycaprolactone (PCL) 
(Alves da Silva et al. 2010) can be used to fabricate fibrous 
scaffolds.
Electrospinning of thermoset polyesters proves to be 
challenging because the postcuring step must be taken 
into consideration. Yi and LaVan (2008) reported on 
the fabrication of PGS nanofibers in random non-woven 
mats by coaxial core/shell electrospinning. Unlike ther-
moplastic polyester, crosslink polyester cannot dissolve 
in solvent; therefore, the electrospinning solution is pre-
pared from PGS prepolymer. There are several problems 
with prepolymer/solvent solution. First, the electrospin-
ning of fibers cannot occur due to low solution viscosity 
caused by the low molecular weight prepolymer. Also, 
nanofibers made from the prepolymer would quickly 
coalesce and melt when they undergo thermal crosslink 
treatment. Therefore, Yi and LaVan (2008) used core/shell 
electrospinning to produce PGS fiber. In this method, a 
carrier polymer, poly(L-lactide), was added into the PGS 
prepolymer/solvent solution to facilitate fiber formation 
and to act as a protective shell that could be removed 
using organic solvent after the PGS fiber was cured. 
Human dermal microvascular endothelial cells (HDMEC) 
were seeded onto PGS nanofiber scaffolds. The scaffolds 
are biocompatible, and the HDMEC attached and spread 
out within the scaffolds. Other studies have also explored 
the use of PGS:PCL (Akhilesh et al. 2015, Rai et al. 2015), 
PGS:poly(vinyl alcohol) (PVA) (Jeffries et al. 2015, Xu et al. 
2015), PGS:poly(3-hydroxybutyrate-co-3-hydroxyvalerate) 
(Kenar et al. 2011), PGS:gelatin (Ravichandran et al. 2011, 
Kharaziha et al. 2013), and PXS:PVA (Li et al. 2014, Li and 
Chen 2015) to prepare fibrous scaffolds.
4 Summary
4.1 Physical properties
The chemical structure and physical properties of pol-
yol-based biodegradable polyesters discussed in this 
review are summarized in Tables 3 and 4, respectively. In 
summary, thermoset polyol-based biodegradable polyes-
ters demonstrate attractive properties and great potential 
to be used in soft tissue engineering. The mechanical 
properties of thermoset polyesters prepared from polyols 
and polyacids mimic the properties of diverse human soft 
tissues where this can be simply done by altering the syn-
thesis parameters such as type of monomers, monomer 
stoichiometry, and reaction conditions. Also,most of the 
polyesters mentioned in this review have glass transition 
temperature below the human body temperature. The 
random crosslink network gives the polyesters flexibility 
and elasticity that resemble those of the ECM.
4.2 Biodegradability and biocompatibility
The in vitro degradation rate and biocompatibility of 
polyol-based polyesters are listed in Table  5. Thermoset 
polyol-based polyesters can easily break down to natural 
metabolic products or monomers by simple hydrolysis. 
Most of these polyesters fully degraded within 1 month, 
while some required more than 3 months. The rate of 
degradation can be tailored by changing the synthesis 
parameters mentioned previously to match the healing 
kinetics of injured tissue. Polyol-based polyesters also 
showed good maintenance of geometry stability during 
degradation due to the polyesters degraded via surface 
erosion. Catalyst-free synthesis method and endoge-
nous monomers are beneficial to the biocompatibility of 
polyol-based polyesters as the degradation products are 
non-cytotoxic and can be removed via human metabolic 
pathway.
4.3 Limitations of polyol-based polyesters
The ideal biomaterial for tissue engineering application 
should be biocompatible and biodegradable, possess 
mechanical properties that mimic the host tissues, and 
support cell attachment and proliferation. However, 
efforts still need to be made to achieve this goal. Although 
polyol-based polyesters demonstrated attractive proper-
ties, these polymers do have several drawbacks. First, 
the processability of these polyesters is relatively poor 
compared to thermoplastic polyesters. Once polyol-based 
polyesters are cured, the geometry cannot be changed. 
Limited information related to the mechanical properties 
of these polyesters after fabrication into porous scaffolds 
was found. Porous structure might decrease the mechani-
cal properties of the polyesters, which will further restrict 
the applications of the polymers. Also, polyol-based poly-
esters released acidic degradation products that could 
trigger unwanted inflammation to host tissue.
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16      W.H. Tham et al.: Polyol-based biodegradable polyesters
Ta
bl
e 4
: 
Ph
ys
ica
l p
ro
pe
rti
es
 o
f p
ol
yo
l-b
as
ed
 p
ol
ye
st
er
s.
Po
ly
m
er
 
E (
M
Pa
)
 
σ (
M
Pa
)
 
ε (
%
)
 
T g
 (°
C)
 
Re
fe
re
nc
es
Po
ly
(g
ly
ce
ro
l s
eb
ac
at
e)
, P
GS
 
0.
28
–1
.5
0
 
0.
28
–0
.7
0
 
12
5–
26
7
 
 < -
80
 
W
an
g 
et
 al
. (
20
02
), 
Po
m
er
an
ts
ev
a 
et
 al
. (
20
09
)
Th
er
m
op
la
st
ic 
po
ly
(g
ly
ce
ro
l s
eb
ac
at
e)
, T
M
PG
S
 
0.
07
–7
.0
5
 
0.
21
–0
.7
0
 
12
–2
36
 
-2
2.
5 
to
 -3
2.
2 
Liu
 et
 al
. (
20
05
, 2
00
7a
,b
)
Po
ly
(g
ly
ce
ro
l s
eb
ac
at
e c
itr
at
e)
, P
GS
C
 
0.
61
–3
.2
6
 
0.
63
–1
.4
6
 
51
–1
70
 
-1
2 
to
 -3
0
 
Liu
 et
 al
. (
20
09
)
Po
ly
(g
ly
ce
ro
l s
eb
ac
at
e l
ac
tic
 a
cid
), 
PG
SL
 
0.
76
–2
.9
4
 
0.
15
–0
.2
1
 
13
3–
20
7
 
NA
 
Su
n 
et
 al
. (
20
08
, 2
00
9)
Po
ly
(g
ly
ce
ro
l d
od
ec
an
ed
io
at
e)
, P
GD
 
1.
08
–1
36
.5
5 
0.
46
–7
.2
0
 
12
3.
2–
22
5 
32
.1
 
M
ig
ne
co
 et
 al
. (
20
09
)
Po
ly
(1
,3
-d
ia
m
in
o-
2-
hy
dr
ox
yp
ro
pa
ne
 p
ol
yo
l s
eb
ac
at
e)
, P
AP
S
 
1.
45
–4
.3
4
 
0.
24
–1
.6
9
 
21
–9
2
 
33
.7
–4
8.
0
 
Be
tti
ng
er
 et
 al
. (
20
08
, 2
00
9)
Po
ly
(x
yl
ito
l s
eb
ac
at
e c
itr
at
e)
-m
et
ha
cr
yla
te
, P
XC
m
a
 
5.
80
 
NA
 
80
 
NA
 
Br
ug
ge
m
an
 et
 al
. (
20
08
a)
Po
ly
(x
yl
ito
l d
ica
rb
ox
yla
te
), 
PX
D
 
0.
3–
14
.7
a
 
 
 
-2
2 
to
 4
6
 
Po
ly
(p
ol
yo
l s
eb
ac
at
e)
, P
PS
 
0.
37
–3
78
 
0.
57
–1
7.
64
 
11
–2
05
 
7.
3–
45
.6
 
Br
ug
ge
m
an
 et
 al
. (
20
08
a,
b,
 2
01
0)
Po
ly
(s
or
bi
to
l c
itr
ic 
se
ba
ca
te
), 
PS
CS
 a
nd
 p
ol
y(
so
rb
ito
l t
ar
ta
ric
 se
ba
ca
te
), 
PS
TS
 
1.
06
–4
62
.6
5 
0.
45
–2
0.
32
 
20
–5
78
 
4.
5–
26
.3
 
Pa
su
pu
le
ti 
an
d 
M
ad
ra
s (
20
11
)
Po
ly
(m
an
ni
to
l c
itr
ic 
di
ca
rb
ox
yla
te
), 
PM
CD
 
8.
25
–6
60
.2
3 
1.
20
–1
2.
52
 
14
–1
80
 
16
.1
–5
8.
5
 
Pa
su
pu
le
ti 
et
 al
. (
20
11
)
Ca
st
or
 o
il-
ba
se
d 
po
ly
(m
an
ni
to
l c
itr
ic 
se
ba
ca
te
), 
Co
PM
CS
 
1.
60
–3
.9
3
 
0.
34
–0
.8
1
 
38
–6
7
 
-2
0 
to
 -2
7
 
Sa
th
is
ku
m
ar
 a
nd
 M
ad
ra
s (
20
11
)
Ri
cin
ol
ei
c a
cid
-b
as
ed
 p
ol
y(
m
an
ni
to
l c
itr
ic 
se
ba
ca
te
), 
RP
M
CS
 
19
.9
0–
80
.1
0 
0.
70
–3
.6
0
 
10
–5
1
 
-0
.4
2 
to
 6
.6
 
Ch
an
do
rk
ar
 et
 al
. (
20
13
)
Sa
lic
yl
ic 
ac
id
-b
as
ed
 p
ol
y(
m
an
ni
to
l s
eb
ac
at
e)
 
n/
a
 
n/
a
 
n/
a
 
17
 
Ch
an
do
rk
ar
 et
 al
. (
20
14
)
Po
ly
(tr
io
l α
-k
et
og
lu
ta
ra
te
), 
PT
K
 
0.
10
–6
57
.4
0 
0.
20
–3
0.
8
 
22
–5
83
 
NA
 
Ba
rre
tt 
an
d 
Yo
us
af
 (2
00
8)
Po
ly
(e
ry
th
rit
ol
 d
ica
rb
ox
yla
te
), 
PE
rD
 
0.
08
–8
0.
37
 
0.
14
–1
6.
65
 
22
–4
66
 
-3
6 
to
 4
 
Ba
rre
tt 
et
 al
. (
20
10
a)
Po
ly
(s
or
bi
to
l i
ta
co
na
te
-co
-s
or
bi
to
l s
uc
cin
at
e)
, P
SI
-co
-S
S
 
11
.2
2
 
2.
05
 
11
9
 
4
 
Ba
rre
tt 
et
 al
. (
20
10
b)
Po
ly
(s
or
bi
to
l s
eb
ac
at
e m
al
at
e)
-h
yd
ro
xy
ap
at
ite
, P
SS
M
-H
A
 
62
7–
10
26
 
16
.2
0–
23
.9
6 
10
–4
9
 
40
–4
3
 
Th
am
 et
 al
. (
20
12
)
Po
ly
(x
yl
ito
l d
od
ec
an
ed
io
at
e)
-h
yd
ro
xy
ap
at
ite
, P
XD
D-
HA
 
NA
 
NA
 
NA
 
42
–4
5b
/5
5c
 
a S
to
ra
ge
 m
od
ul
us
; b
cr
ys
ta
lli
za
tio
n 
te
m
pe
ra
tu
re
 (T
c);
 c m
el
tin
g 
te
m
pe
ra
tu
re
 (T
m
).
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W.H. Tham et al.: Polyol-based biodegradable polyesters      17
Ta
bl
e 5
: 
De
gr
ad
at
io
n 
ra
te
s a
nd
 b
io
co
m
pa
tib
ili
ty
 o
f p
ol
yo
l-b
as
ed
 p
ol
ye
st
er
s i
n 
vit
ro
.
Po
ly
m
er
 
M
as
s l
os
s
 
Ce
ll 
type
 
M
aj
or
 re
su
lts
 
Re
fe
re
nc
es
Po
ly
(g
ly
ce
ro
l s
eb
ac
at
e)
, P
GS
 
17
%
 a
fte
r 6
0 
da
ys
 in
 P
BS
 
NI
H 
3T
3 
fib
ro
bl
as
t
 
Ce
lls
 sh
ow
ed
 fa
st
 p
ro
lif
er
at
io
n 
wi
th
 n
or
m
al
 m
or
ph
ol
og
ie
s 
co
m
pa
re
d 
to
 P
LG
A 
as
 p
os
iti
ve
 co
nt
ro
l
 
W
an
g 
et
 al
. (
20
02
)
Th
er
m
op
la
st
ic 
po
ly
(g
ly
ce
ro
l s
eb
ac
at
e)
, 
TM
PG
S
 
30
–3
6%
 a
fte
r 2
8 
da
ys
 in
 P
BS
 
n/
a
 
n/
a
 
Liu
 et
 al
. (
20
07
a,
b)
Po
ly
(g
ly
ce
ro
l s
eb
ac
at
e c
itr
at
e)
, P
GS
C
 
13
–1
8%
 a
fte
r 2
8 
da
ys
 in
 P
BS
 
n/
a
 
n/
a
 
Liu
 et
 al
. (
20
09
)
Po
ly
(g
ly
ce
ro
l s
eb
ac
at
e l
ac
tic
 a
cid
), 
PG
SL
 
22
–4
3%
 a
fte
r 8
0 
da
ys
 in
 P
BS
 
SN
L m
ou
se
 fi
br
ob
la
st
 
Si
gn
ifi
ca
nt
 im
pr
ov
em
en
t i
n 
ce
ll 
pr
ol
ife
ra
tio
n 
wi
th
 n
or
m
al
 
m
or
ph
ol
og
ie
s c
om
pa
re
d 
wi
th
 P
GS
 
Su
n 
et
 al
. (
20
09
a,
b)
, C
he
n 
et
 al
. 
(2
01
1)
Po
ly
(g
ly
ce
ro
l d
od
ec
an
ed
io
at
e)
, P
GD
 
87
%
 a
fte
r 9
0 
da
ys
 in
 P
BS
 
Hu
m
an
 a
or
tic
 
fib
ro
bl
as
t
 
Ce
lls
 a
dh
er
e,
 g
ro
w,
 a
nd
 re
m
ai
n 
m
et
ab
ol
ica
lly
 a
ct
ive
 in
 
cu
ltu
re
 
M
ig
ne
co
 et
 al
. (
20
09
)
Po
ly
(1
,3
-d
ia
m
in
o-
2-
hy
dr
ox
yp
ro
pa
ne
 
po
ly
ol
 se
ba
ca
te
), 
PA
PS
 
43
–9
7%
 a
fte
r 6
 w
ee
ks
 in
 
so
di
um
 a
ce
ta
te
 b
uf
fe
r
 
Hu
m
an
 fo
re
sk
in
 
fib
ro
bl
as
t
 
Ce
lls
 a
tta
ch
ed
 a
nd
 ex
hi
bi
te
d 
si
m
ila
r m
or
ph
ol
og
y t
o 
ce
lls
 
gr
ow
n 
on
 P
LG
A 
co
nt
ro
l
 
Be
tti
ng
er
 et
 al
. (
20
08
)
Po
ly
(x
yl
ito
l s
eb
ac
at
e c
itr
at
e)
-
m
et
ha
cr
yla
te
, P
XC
m
a
 
n/
a
 
Hu
m
an
 fo
re
sk
in
 
fib
ro
bl
as
t
 
No
 ce
ll 
at
ta
ch
m
en
t o
n 
sp
ec
im
en
s,
 a
nd
 ce
lls
 w
er
e n
ot
 
co
m
pr
om
is
ed
 in
 th
ei
r m
ito
ch
on
dr
ia
l m
et
ab
ol
is
m
 
Br
ug
ge
m
an
 et
 al
. (
20
08
a)
Po
ly
(x
yl
ito
l d
ica
rb
ox
yla
te
), 
PX
D
 
4–
10
0%
 a
fte
r 7
 d
ay
s i
n 
PB
S
 
Ce
rv
ica
l c
an
ce
r c
el
ls
 
(H
eL
a)
 
Su
pp
or
t c
el
l a
tta
ch
m
en
t a
nd
 p
ro
lif
er
at
io
n
 
Da
sg
up
ta
 et
 al
. (
20
14
)
Po
ly
(p
ol
yo
l s
eb
ac
at
e)
, P
PS
 
1–
22
%
 a
fte
r 1
05
 d
ay
s i
n 
PB
S
 
Hu
m
an
 fo
re
sk
in
 
fib
ro
bl
as
t
 
PS
S 
su
pp
or
t c
el
lu
la
r a
tta
ch
m
en
t e
xc
ep
t f
or
 P
SS
1:
1 
an
d 
PM
S1
:1
 
Br
ug
ge
m
an
 et
 al
. (
20
08
b)
Po
ly
(s
or
bi
to
l c
itr
ic 
se
ba
ca
te
), 
PS
CS
 a
nd
 
po
ly
(s
or
bi
to
l t
ar
ta
ric
 se
ba
ca
te
), 
PS
TS
 
56
–1
00
%
 a
fte
r 6
 d
ay
s;
 5
2–
10
0%
 a
fte
r 6
 w
ee
ks
 in
 P
BS
 
n/
a
 
n/
a
 
Pa
su
pu
le
ti 
an
d 
M
ad
ra
s (
20
11
)
Po
ly
(m
an
ni
to
l c
itr
ic 
di
ca
rb
ox
yla
te
), 
PM
CD
 
45
–1
00
 a
fte
r 3
 h
; 5
6–
84
%
 
af
te
r 4
 d
ay
s i
n 
PB
S
 
n/
a
 
n/
a
 
Pa
su
pu
le
ti 
et
 al
. (
20
11
)
Ca
st
or
 o
il-
ba
se
d 
po
ly
(m
an
ni
to
l c
itr
ic 
se
ba
ca
te
), 
Co
PM
CS
 
80
–1
00
%
 a
fte
r 2
1 
da
ys
 in
 
PB
S
 
Hu
m
an
 fo
re
sk
in
 
fib
ro
bl
as
t
 
Ce
ll 
pr
ol
ife
ra
tio
n 
wi
th
 sp
in
dl
e-
sh
ap
e m
or
ph
ol
og
y a
nd
 
co
m
pl
et
e c
on
flu
en
ce
 a
fte
r 7
 d
ay
s
 
Sa
th
is
ku
m
ar
 a
nd
 M
ad
ra
s (
20
11
), 
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th
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m
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 et
 al
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20
12
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 p
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 et
 al
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20
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lic
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 p
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Ch
an
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 et
 al
. (
20
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ly
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-k
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ls
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un
ab
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tta
ch
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r p
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rre
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d 
Yo
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 (2
00
8)
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 P
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m
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th
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s f
ro
m
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ia
cid
s w
ith
 
an
 ev
en
 n
um
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iff
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tia
tio
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rre
tt 
et
 al
. (
20
10
a)
Po
ly
(s
or
bi
to
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ta
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te
-co
-s
or
bi
to
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cc
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SI
-co
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sp
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od
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ox
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fte
r 3
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ay
s d
ue
 to
 
de
gr
ad
at
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od
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ts
 in
cr
ea
se
d 
th
e a
cid
ity
 o
f t
he
 m
ed
iu
m
 
Ba
rre
tt 
et
 al
. (
20
10
b)
Authenticated | mat.uzir@cheme.utm.my author's copy
Download Date | 1/12/16 8:58 AM
18      W.H. Tham et al.: Polyol-based biodegradable polyesters
5 Conclusion
Most of the biodegradable materials currently on the 
market are based on natural polymers such as collagen 
andsynthetic polymers such as poly(α-esters). Advances 
in biomedical research such as tissue engineering and 
drug delivery led to the development of a wide range of 
thermoset biodegradable polyesters synthesized from cat-
alyst-free polyesterification in the past few years. Biocom-
patible polyesters have been synthesized from monomers 
that are endogenous to human metabolism that reduce the 
toxicity of the degradation products. Thermoset polyes-
ters developed from this method are simple, effective, and 
of low cost. These polyesters showed excellent properties 
such as biocompatibility, biodegradability, elastomeric-
ity, and tunable mechanical properties and degradation 
rates. Future works should be focused on designing more 
novel polyesters for tissue engineering application and 
modifying existing polyesters to achieve better degrada-
tion and physical properties to elicit favorable biological 
responses.
Acknowledgments: The authors wish to acknowledge 
the Exploratory Research Grant Scheme (ERGS) Vote No: 
4L031 and Prototype Research Grant Scheme (PRGS) Vote 
No: 4L608 by Universiti Teknologi Malaysia from the Min-
istry of Science, Technology and Innovation (MOSTI).
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