SYNTHESIS AND CHARACTERIZATION OF BIODEGRADABLE

POLY(XYLITOL SEBACATE DODECANOATE)/ NANO-HYDROXYAPATITE

COMPOSITES FOR POTENTIAL USED IN BIOMEDICAL APPLICATIONS

NOOR FAEZAH BINTI MOHD SANI

UNIVERSITI TEKNOLOGI MALAYSIA

SYNTHESIS AND CHARACTERIZATION OF BIODEGRADABLE

POLY(XYLITOL SEBACATE DODECANOATE)/NANO-HYDROXYAPATITE

COMPOSITES FOR POTENTIAL USED IN BIOMEDICAL APPLICATIONS

NOOR FAEZAH BINTI MOHD SANI

A dissertation submitted in fulfillment of the

requirements for the award of the degree of

Master of Science (Polymer Technology)

Faculty of Chemical Engineering

Universiti Teknologi Malaysia

OCTOBER 2013

To my beloved parents and family

ACKNOWLEDGEMENT

First and foremost, all praises be to Allah S.W.T, the Almighty, for His

blessings and guidance for instilling me the strength and patience in completion of

this research project.

I would like to express my very great appreciation to my supervisor,

Associate Professor Dr. Mat Uzir Wahit and my examiner, Dr. Nadia Adrus for the

encouragement, valuable guidance and advice in clarifying my doubts throughout the

period of completing this study.

My sincere appreciation also goes to all my research group members for their

help and support especially to Tham Weng Hong, Mohammad Soheilmoghaddam,

Izyan Bt Yusoff, Wong Tuck Whye, Lee Xiau Yeen and Baiti Bt Hanid.

Furthermore, I would like to thank to lab assistants who help guiding me operated the

laboratory instrument and equipments.

Many thanks also to my beloved parents, my family and friends who had

support and keep me focused on my study.

Last but not least, I would like also to extend my appreciation to Universiti

Teknologi Malaysia (UTM) for providing me with the facilities vital to the

completion of this project.

ABSTRACT

Xylitol-based polyesters such as poly(xylitol sebacate) (PXS) are said to be

the best candidates for tissue engineering due to its tunable mechanical and

degradation properties. In this study, dodecanedioic acid (DDA) was added into PXS

as the additional monomer to increase the strength. Novel poly(xylitol sebacate

dodecanoate) (PXSD) polymers was synthesized by using polycondensation method

for potential used in tissue engineering. The starting materials for synthesizing PXSD

are xylitol, sebacic acid (SA) and DDA and the ratio was varied (xylitol: SA: DDA),

PXSD 1 (1:0.25:0.75) PXSD 2 (1:0.5:0.5) and PXSD 3 (1:0.75:0.25). The mixture

synthesized at 120 ⁰C for 24 hours under the present of nitrogen gas. After that it was

further cured in an oven at 100 ⁰C for 4 days. From the tensile test data, PXSD 1 was

selected as the matrix to prepare PXSD/n-HA composite. Thermal stability and

melting temperature slightly increased with the increasing in DDA ratio. Polymer

crystallinity, mechanical properties such as tensile strength, percentage strain at

break, Young’s modulus and degradation rate of the polymer was also controlled by

the monomer ratio between SA and DDA. Increasing the DDA content resulted in

highly ordered structure, improved mechanical properties and reduced erosion time.

Much faster degradation rate was found in PXSD 3 compared to the more crystalline

polymer of higher DDA content. Another objective was to investigate the effect of n-

HA amount to the polymer properties and it was varied to 5, 10, 15 and 20 wt.%. By

increasing the n-HA within the matrix, tensile strength and Young’s modulus were

increased, but the percentage strain at break was reduced. The thermal properties

showed no significant changes and distribution of the filler particles become well as

the n-HA loadings were increased.

ABSTRAK

Poliester yang berasaskan xylitol seperti poly(xylitol sebakat) (PXS)

dikatakan bersesuaian diaplikasikan sebagai bahan untuk kegunaan kejuruteraan tisu

kerana sifat mekanik dan kadar degradasi yang boleh dimanipulasi. Di dalam

penyelidikan ini, asid dodekanedioik (DDA) telah dicampurkan ke dalam PXS

sebagai monomer tambahan untuk meningkatkan kekuatan bahan. Polimer PXSD

disintesis menggunakan teknik polikondensasi. Bahan pemula yang digunakan untuk

menghasilkan PXSD ialah xylitol, asid sebakat (SA) dan DDA dengan nisbah

berlainan seperti (xylitol: SA: DDA); PXSD 1 (1: 0.25: 0.75), PXSD 2 (1: 0.5: 0.5)

dan PXSD 3 (1: 0.75: 0.25). Campuran ini disintesis pada 120 ⁰C selama 24 jam

dengan kehadiran gas nitrogen, diikuti dengan pengawetan di dalam ketuhar selama

4 hari pada 100 ⁰C. Kestabilan haba dan suhu lebur menunjukkan sedikit

peningkatan apabila nisbah DDA ditingkatkan. Kehabluran, sifat mekanik dan

degradasi polimer dikawal oleh nisbah monomer antara SA dan DDA. Peningkatan

nisbah DDA menghasilkan menambahkan struktur hablur polimer, meningkatkan

sifat mekanik dan melambatkan masa degradasi. PXSD 3 yang mempunyai nisbah

DDA paling sedikit didapati mempunyai kadar degradasi yang paling cepat jika

dibandingkan dengan polimer yang mempunyai struktur hablur yang tinggi. Objektif

lain di dalam penyelidikan ini adalah untuk mengkaji kesan jumlah nano-

hidroksiapatite (n-HA) terhadap sifat polimer yang terhasil. Jumlah n-HA di dalam

sistem komposit divariasikan kepada 5, 10, 15 dan 20 wt%. Daripada data tegangan

yang diperolehi, PXSD 1 telah dipilih sebagai matrik untuk menghasilkan PXSD/HA

komposit nano. Peningkatan jumlah n-HA di dalam matrik menambahkan kekuatan

tegangan dan modulus, tetapi peratus untuk terikan telah menurun. Sifat termal

menunjukkan perubahan yang tidak begitu ketara dan taburan partikel pengiso

bertambah baik apabila jumlah n-HA telah ditingkatkan.

TABLE OF CONTENTS

CHAPTER TITLE PAGE

DECLARATION ii

DEDICATION iii

ACKNOWLEDGEMENT iv

ABSTRACT v

ABSTRAK vi

TABLE OF CONTENTS vii

LIST OF TABLES xi

LIST OF FIGURES xii

LIST OF ABBREVIATIONS xv

LIST OF SYMBOLS xvii

LIST OF APPENDICES xviii

1 INTRODUCTION 1

1.1 Research Background 1

1.2 Problem Statement 3

1.3 Objective of Research 5

1.4 Scopes of Study 5

2 LITERATURE REVIEW 7

2.1 Introduction 7

2.2 Biodegradable Polymer for Scaffolds 8

2.3 Nano-hydroxyapatite (n-HA) 12

2.4 Method of Degradation 13

2.5 Aliphatic Polyesters 14

2.6 Xylitol 15

2.7 Sebacic Acid 16

2.8 Dodecanedioic Acid 17

2.9 Polycondensation Reaction 17

2.10 Recent Developed Biodegradable Polyesters 18

2.10.1 Poly(xylitol sebacate) (PXS) 18

2.10.2 Poly(1,2-propanediol-sebacate)-citrate)

(PPSC)

19

2.10.3 Poly(L-lactide)/nano-hydroxyapatite

(PLLA)

20

2.10.4 Poly(octanediol citrate sebacate)

(POCS)

20

2.10.5 Poly(sorbitol sebacate

malate)/hydroxyapatite (PSSM/HA)

composites

21

2.10.6 Polydiol citrate/hydroxyapatite 21

2.10.7 Poly(sorbitol sebacate citrate) (PSCS)

and poly(sorbitol sebacate tartarate)

(PSTS)

22

3 METHODOLOGY 23

3.1 Materials 23

3.2 Preparation of Pre-polymer 24

3.3 Preparation of PXSD/ n-HA Composites 25

3.4 Characterization and Testing 26

3.4.1 Fourier Transform Infrared

Spectroscopy (FTIR)

26

3.4.2 Differential Scanning Calorimeter

(DSC)

26

3.4.3 Thermogravimetric Analysis (TGA) 27

3.4.4 Field Emission Scanning Electron

Micrometer (FESEM)

27

3.4.5 X- Ray Diffraction (XRD) 27

3.4.6 Tensile Test 28

3.4.7 In Vitro Degradation Test 28

3.5 Flow Chart 30

4 RESULTS AND DISCUSSION 31

4.1 Synthesis and selection of PXSD Pre-polymer 31

4.1.1 Synthesis of PXSD polyester and

PXSD/n-HA composite

31

4.1.2 Effect of Monomer Ratio on

Mechanical Properties

32

4.1.2.1 Tensile Strength 32

4.1.2.2 Elongation at Break 33

4.1.2.3 Young’s Modulus 34

4.2 Characterization of PXSD polyester and PXSD/n-

HA composite

36

4.2.1 Fourier Transform Infrared

Spectrometer (FTIR)

36

4.2.2 Differential Scanning Calorimetry

(DSC)

38

4.2.3 Thermogravimetric Analysis (TGA) 41

4.3 Morphological Assessment of Pure PXSD and

PXSD/n-HA Composites.

47

4.3.1 Field Emission Scanning Electron

Microscopy (FESEM)

47

4.3.2 X- Ray Diffraction (XRD) 49

4.4 Effect of Different Amount of nano-

Hydroxyapatite on Mechanical Properties of

PXSD/n-HA composites

53

4.4.1 Tensile Strength 53

4.4.2 Elongation at Break 54

4.4.3 Young’s Modulus 55

4.5 In Vitro Degradation 56

4.5.1 Weight Loss of PXSD Polyesters and

PXSD/n-HA composites in PBS

56

4.5.2 Water Uptake During The Mass Loss

Process

59

4.5.3 Changes in pH Value of PBS Soaked

with PXSD polyesters and PXSD/n-HA

61

Composites.

4.5.4 Fast Degradation in Sodium Hydroxide

(NaOH)

63

5 CONCLUSION AND RECOMMENDATIONS 66

5.1 Conclusions 66

5.2 Recommendations 67

REFERENCES 68

APPENDICES A-D 72-78

LIST OF TABLES

TABLE NO. TITLE PAGE

2.1 Mechanical properties of natural tissues and

polyesters

11

3.1 Formulation of poly(xylitol sebacate

dodecanoate) (PXSD) polyester

25

3.2 Amount of n-HA in poly(xylitol sebacate

dodecanoate) (PXSD)/n-HA composite

26

4.1 Degradation temperature and percentage of

degradation residue of PXSD polyesters and

PXSD/n-HA composites obtained from TGA

curve

42

4.2 Percentage of crystallinity in PXSD polyesters

and PXSD/n-HA composites

50

LIST OF FIGURES

FIGURE NO. TITLE PAGE

2.1 Schematic diagram of (a) surface erosion (b)

bulk erosion

14

2.2 Chemical structure of xylitol 16

2.3 Chemical structure of sebacic acid 16

2.4 Chemical structure of dodecanedioic acid 17

2.5 General synthetic scheme for PXS elastomers. 19

3.1 Flow chart of pre-polymer and composite

preparation.

30

4.1 Synthesis of PXSD polymer from xylitol,

sebacic acid and dodecanedioic acid.

32

4.2 Effect of variation in monomer ratio on tensile

strength of pure PXSD polyesters.

33

4.3 Effect of variation in monomer ratio on

percentage strain at break of pure PXSD

polyesters.

34

4.4 Effect of variation in monomer ratio on

Young’s modulus of pure PXSD polyesters.

35

4.5 The shifting of hydroxyl group (OH) in pre-

polymer and pure PXSD polyesters’ FTIR

spectra.

36

4.6 The FTIR spectra of pre-polymer and pure

PXSD polyesters.

37

4.7 The FTIR spectra of PXSD/n-HA composites

compare to PXSD 1 and spectra for n-HA

powder.

38

4.8 DSC curves of PXSD polyesters. 39

4.9 DSC curves of PXSD/n-HA composites

compare to PXSD 1.

40

4.10 Images of the samples before and after they

were heated in the oven above their crystalline

deformation temperatures: (a)PXSD 1

(b)PXSD 2 and (c)PXSD 3.

41

4.11 TGA and DTG curves of synthesized PXSD

polyesters.

43

4.12 TGA curve of PXSD/n-HA composites

compare to pure PXSD 1.

44

4.13 TGA curves of PXSD/n-HA composites. 45

4.14 FESEM micrographs of the freeze- fractured

surfaces of (a) pure PXSD 1 and PXSD/n-HA

composites containing (b) 5 wt% n-HA (c) 10

wt% n-HA (d) 15 wt% n-HA and (e) 20 wt%

n-HA.

48

4.15 XRD diffractogram of PXSD polyesters. 49

4.16 XRD diffractogram PXSD/n-HA composites

compare to PXSD 1.

51

4.17 XRD diffractograms of n-HA powder. 52

4.18 Schematic of the heterogenous nucleation

process.

53

4.19 Effect of n-HA content in PXSD/n-HA

composites on tensile strength.

54

4.20 Effect of n-HA content in PXSD/n-HA

composites on percentage strain at break.

55

4.21 Effect of n-HA content in PXSD/n-HA

composites on Young’s modulus.

56

4.22 Mass remaining of representative PXSD

polyesters versus hydrolysis time.

57

4.23 Mass remaining of representative PXSD/n-HA

composites versus hydrolysis time.

58

4.24 Water uptake of representative PXSD

polyesters versus hydrolysis time.

60

4.25 Water uptake of representative PXSD/n-HA

composites versus hydrolysis time.

61

4.26 Changes in pH value of PBS soaked with

PXSD polyesters.

62

4.27 Changes in pH value of PBS soaked with

PXSD/n-HA composites.

63

4.28 Mass remaining PXSD polyesters and in 0.1M

NaOH solution.

64

4.29 Mass remaining of PXSD/n-HA composites

compare to PXSD 1 in 0.1M NaOH solution.

65

LIST OF ABBREVIATIONS

C - Carbon

CA - Citric acid

COOH - Carboxylic acid group

DDA - Dodecanedioic acid

DSC - Differential scanning calorimetry

ECM - Extracellular matrix

FDA - Food and Drug Administration

FESEM - Field emission scanning electron microscopy

FTIR - Fourier transform infrared spectroscopy

HA - Hydroxyapatite

NaOH - Sodium hydroxide

n-HA - Nano-hydroxyapatite

OH - Hydroxyl group

PBS - Phosphate buffer saline

PCL - Poly(caprolactone)

PGA - Poly(glycerol acid)

PGD - Poly(glycerol dodecanoate)

PGS - Poly(glycerol sebacate)

PLA - Poly(lactic acid)

PLGA - Poly(lactide-co- glycolide)

PPS - Poly(polyol sebacate)

PPSC - Poly(1,2- propanediol- sebacate- citrate)

PTFE - Polytetrafluoroethylene

PXS - Poly(xylitol sebacate)

PXSD - Poly(xylitol sebacate dodecanoate)

PXSD/n-HA - Poly(xylitol sebacate dodecanoate)/ nano-hydroxyapatite

SA - Sebacic acid

TE - Tissue engineering

Tg - Glass transition temperature

TGA - Thermogravimetric analysis

Tm - Melting temperature

XRD - X- ray diffraction

LIST OF SYMBOLS

Aa - Area of amorphous region

Ac - Area of crystalline region

E - Young’s modulus

Eb - Elongation at break

N2 - Nitrogen

T10% - Degradation temperature at 10% mass loss.

Wo - Initial mass

WD - Mass of dried sample

WT - Mass at certain time point

Wt% - Weight percent

Xc - Percentage of crystallinity

LIST OF APPENDICES

APPENDIX TITLE PAGE

A Calculation of weight for each monomer and the

total weight

72

B Calculation of crystallinity in pure PXSD and

PXSD/n-HA composites

73

C Mechanical properties of PXSD polymers and

PXSD/n-HA composites.

75

D Amount of mass remaining and water uptake of

degradation in PBS and NaOH solution.

76

CHAPTER 1

INTRODUCTION

1.1 Research Background

Methods to regenerate and restore bone tissue to its functional state have

became a clinical necessity as the increase of aging population. This is because, with

an advancing age, the imbalance of bone resorption and formation can lead to bone

disease such as osteoporosis (Green et al., 2002). Currently, the surgeon use donor

tissue for bone repair which are known as allogenic and autologous. Allogenic is the

process of cells transplant from different individual of the same species, while in

autologous technique the cell donor and recipient is the same person. However, both

techniques suffer from limitations. The current clinical “gold standard”, autografting,

requires a second surgery site, which is expensive and often associated with donor

site morbidity, pain, infection, and hematoma formation. Allografting carries the

potentials risk of immune rejection, as well as a lessening or even complete loss of

bone inductive factor (Petricca et al., 2002).

Construction of scaffolds for tissue engineering is considered as the best

solution of the various current treatment drawbacks. Through tissue engineering,

researchers seek to regenerate human tissue, such as bone and cartilage that has been

damaged by injury or disease. Over the time, the artificial scaffold which is lattice-

like structure will resorbs into the body and leaving behind only the natural tissue

(Pallua et al., 2011).

Biodegradable elastomers are said to be the best candidates for tissue

engineering applications since many tissues in the body have elastomeric properties,

and these kind of material can mimic the structure of bone. Polyester based

biodegradable polymer has been synthesized in this research by using xylitol, sebacic

acid (SA), and dodecanedioic acid (DDA). According to the previous literature

reported by Francesco et al., (2009) three features of polyester elastomers including

stable three dimensional network structure, certain elasticity which can provide

mechanical stimulation for tissue engineering constructs, and appropriate mechanical

strength especially matching with soft tissues and organ bodies have make it very

suitable to be developed. Xylitol is a very versatile polymer platform use as the

central monomer because it is composed of metabolites endogenous to the

mammalian organism, yielding hydrogels with tunable mechanical properties and in

vivo degradation (Bruggeman et al., 2008). In addition, the mechanical properties of

xylitol based elastomers are correspond to biologically relevant values that fall close

to or are equal to those of various tissues such as acellular peripheral nerves, small

diameter arteries, cornea and intervertebral discs (Bruggeman et al., 2008).

Currently, the most widely used implantable degradable polymer are the poly

(α-esters), in particular poly(glycolic acid) (PGA) and poly(lactic acid) (PLA) and

their copolymers poly(lactic/glycolic) acid (PLGA). These FDA approved polymers

are used in resorbable sutures and injectable drug delivery system. However these

polymers display bulk erosion characteristics (Gopferich., 1996). Xylitol based

polyester are said to be the best candidates since the mechanical and degradation rate

can be tuned by simply adjust the monomer ratio. Poly(xylitol sebacate) (PXS) was

previously synthesized by Bruggeman et al., (2008) by reacting xylitol and SA via

polycondensation reaction without the use of catalyst. However, PXS is very soft

with a range of Young’s modulus of 0.82 ± 0.15 to 5.33 ± 0.40 MPa. Therefore, an

additional monomer, DDA which has 12 carbon (12 C) atoms and two carboxylic

groups (COOH) will be added to the reaction. It is anticipated that, it will improve

the mechanical properties. Previously, DDA had been used as acid monomer to

develop poly(glycerol-dodecanoate) (PGD), high modulus and high elongation at

break were achived (Migneco et al., 2009). Besides that, Djordjevic et al., 2010, had

reported that the combination of multifunctional acids, citric acid (CA) and SA yield

hydrophilic polyesters with different properties by varying its mole ratio.

Nano-hydroxyapatite (n-HA), a type of inorganic bone mineral was used as

filler in this research to further improve the mechanical and biological properties of

the scaffold such as to impart osteoconductivity to the polymers (Qiu et al., 2006). In

addition to increase the modulus, HA has biocompatibility with several types of cells

such as osteoblast, osteoclast, fibroblast and periodontal ligaments (Correlo et al.,

2005). Elastomer composite with HA may be a competent candidate for application

in tissue engineering scaffold because its certain elastic properties can provide

mechanical stimulation for tissue engineering construct, improved mechanical

strength, adjustable biodegradation and comparably stable shape (Liu et al., 2009). In

this project, poly(xylitol sebacate dodecanedioate) (PXSD) with three different ratios

were synthesized. n-HA was incorporated to further improve the mechanical

properties and reduce the degradation rate. To our knowledge, the research and

synthesis of PXSD polymer and PXSD/n-HA composites, have not been reported in

the present day.

1.2 Problems Statement

In previous literature, PXS was synthesized by using xylitol and sebacic acid

as starting monomer (Bruggeman et al.,2010). Xylitol-based polymers have been

preferably employed by Bruggemann and coworkers since it has tunable mechanical

and degradation properties by simply adjusting the monomer ratio. However, PXS is

very soft with a Young’s modulus of only 0.82 ± 0.15 MPa. Due to this inadequate

strength property DDA will be added as the third monomer to increase the strength

and perhaps reduce the degradation rate by reducing the amount of degrading agent

to permit into the polymer which can be achieved by the formation of crystalline

segments. According to Djordjevic et al., (2010), the use of additional acid reacts

with multifunctional alcohols in catalyst free polycondensation reactions, will yield

hydrophilic polyesters with high degree of elasticity and therefore produce polymer

with high menchanical properties. In addition to mechanical properties and

degradation time, it is also an advantage for the polymer to have “dual behavior”

(plastic-elastomeric transition) to enhance surgical implantation since it is much

easier to position correctly a stiff device than a soft one, and this can be achieved by

using a bulky polymer backbone (12 C dicarboxylic acid) (Migneco et al., 2009).

In order to lower the degradation rate, n-HA was added to counteract with the

degradation residue of the polymer and also to make it to more compatible for bone

cells (Liang et al., 2010). The effect of loading n-HA with different amount into

PXSD has not yet been reported. It is expected that mechanical and degradation

properties will be improved since it can affect the composites’ morphology. Similar

to other study, this research is performed in comparison to PLGA as control since

PLGA has been used clinically over a very long period providing substantial data

regarding their performances as biomaterials.

Several questions need to be answered are listed below:

1. What is the effect of different mole ratio of xylitol: SA: DDA on the

mechanical properties and rate of degradation of PXSD elastomers.

2. What is the effect of different amount of n-HA on the mechanical properties

and rate of degradation of composites.

1.3 Objectives of Research

The main objective of this research is to synthesis PXSD polyester and PXSD

composite reinforced with n-HA. The PXSD/n-HA composites have the potential

application in tissue engineering as a scaffold material. Other objectives are listed

below:

1. To determine the best monomer ratio of SA and DDA (xylitol: SA: DDA)

(1:0.25:0.75, 1:0.5:0.5, and 1:0.75:0.25) on the mechanical properties and

degradation rate of the elastomers.

2. To investigate the effect of increasing weight percent of n-HA (5, 10, 15, and

20 wt%) on the mechanical properties and degradation rate of

composites.

1.4 Scopes of the Study

The scopes of this research will cover the following:

1. Polycondensation reaction will be used to produce PXSD elastomers.

Fourier transform infra-red (FTIR) spectroscopy will be used to identify the

chemical bonds of the elastomers and composites.

2. Differential scanning spectroscopy (DSC) and Thermogravimetric analysis

(TGA) will be used to study the thermal properties of elastomers and

composites.

3. Field Emission Scanning electron microscope (FESEM) and x-ray diffraction

(XRD) will be used to study the morphology of the elastomers and

composites.

4. Tensile test will be carried out to evaluate the mechanical properties of

elastomers and composites.

5. In vitro degradation test will be carried out to determine the rate of

degradation of the elastomers and composites.

REFERENCES

Ahmad.R, R., Adnan, R., Abu.B, M., and Masudi, S.M. (2011). Synthesis and

characterization of pure nanoporous hydroxyapatite. Chemical sciences. 22,

25-37.

Bruggeman, J.P., Bettinger, C.J., L.E. Nijst, C.L.E., Daniel, S., Kohane, and Langer,

R. (2008). Biodegradable Xylitol-based polymers. Advanced materials. 20,

1922-1927.

Bruggeman, J.P., Bruin, B.J., Bettinger, C.J., Langer, R. (2008). Biodegradable

poly(polyol sebacate) polymers. Biomaterials. 29, 4726-4735.

Bruggeman, J.P., Bettinger, C.J., and Langer,R. (2010). Biodegradable xylitol- based

elastomers: In vivo behavior and biocompatibility. Journal of Biomedical

Materials Research. 95, 92-103.

Calandrelli, L., Immirzi, B., Malinconico, M., Volpe, M.G., Oliva, A., and Ragione,

F.D. (2000). Preparation and characterization of composites based on

biodegradable polymers for “in vivo” application. Polymer. 41, 8027-8033.

Cho,J., Boccaccini,A.R., and Shaffer, M.S.P. (2009). Ceramic matrix composites

containing carbon nanotubes. Material Science. 44, 1934-1951.

Chung, D.D.L. (2000). Thermal analysis of carbon fiber polymer-matrix composites

by electrical resistance measurement. Themochimica Acta. 364, 121-132.

Chung, E.J., Sugimoto, M.J., and Ameer, G.A. (2011). The role of hydroxyapatite in

citric acid- based nanocomposites: Surface characteristics, degradation, and

osteogenicity in vitro. Biomaterials.

Correlo, V.M., Boesel, L.L., Bhattacharya, M., Mano.F, J., Neves.M, N., and Reis,

R.L. (2005). Hydroxyapatite reinforced chitosan and polyester blends for

biomedical applications. Macromolecular Materials and Engineering. 290,

1157-1165.

Correlo, V.M., Pinho, E.D., Pashkuleva, I., Bhattacharya, M., Neves, N.M., and Reis,

L.R. (2007). Water absorption and degradation characteristics of chitosan-

based polyesters and hydroxyapatite composites. Macromolecular

Bioscience. 7, 354–363.

Djordjevic, I., Choudhury, N.R., K.D, Naba., Kumar, S. (2010). Poly(octanediol- co-

(citric acid)- co- (sebacic acid) elastomers: novel bio- elastomers for tissue

engineering. Society of Chemical Industry. 60, 333-343. Elkayar, A., Elshazly, Y., and Asaad, M. (2009). Properties of hydroxyapatite from

bovine teeth. Bone and Tissue Regeneration Insight. 2, 31-36.

Hasegawa, S., Ishii., Tamura, J., Furukawa, T., Neo, M., Matsusue, Y., Shikinami,

Y., Okuno, M., and Nakamura, T. (2006). A 5- 7 year in vivo study of high-

strength hydroxyapatite/ poly(L- lactide) composite rods for the internal

fixation of bone fractures. Biomaterials. 27, 1327-1332.

Kharkwal.H., Bala,K., and Katare, D.P. (2011). Biodegradable polymers, role in

enhancing bioavailability of drug. Biomedical and Pharmaceutical Sciences.

5, 01-11.

Kordestani, S.S., Hanna, S., and Windle, A.H. (2000). The role of crystallinity in the

deformation of main-chain liquid-crystalline copolyesters. Polymer. 41,

6616-6626.

Lee, L.Y., Wu, S.C., Fu, S.S., Zeng, S.Y., Leong, W.S., and Tan, L.P. (2009).

Biodegradable elastomer for soft tissue engineering. European Polymer

Journal. 45, 3249–3256.

Lei, L., Li, L., Zhang, L., Chen, C., and Tian, W. (2009). Structure and performance

of nano- hydroxyapatite filled biodegradable poly(1,2- propanediol- sebacate-

citrate) elastomers. Polymer degradation and stability. 94, 1494-1502.

Liang, S.L., Cook, W.D., Thouas, G.A., and Chen, Q.Z. (2010). The mechanical

characteristics and in vitro biocompatibility of poly(glycerol sebacate)-

bioglass elastomeric composites. Biomaterials. 31, 8516-8529.

Liu, Q., Jiang, L., Shi, R., and Zhang, L. (2012). Synthesis, preparation, in vitro

degradation, and application of novel degradable bioelastomers. Polymer

sciences. 37, 715-765.

Liu, Q., Wu, J., Tan, T., Zhang, L., Chen, D., and Tian, W. (2009). Preparation,

properties and cytotoxicity evaluation of a biodegradable polyester elastomer

composite. Polymer degradation and stability. 94, 1427-1435

Migneco, F., Huang, Y.C., Birla, R.K., and Hollister, S.J. (2009). Poly(glycerol-

dodecanoate), a biodegradable polyester for medical devices and tissue

engineering scaffolds. Biomaterials. 30, 6479-6484.

Mukhodpadhyay, S.K., Basu, D., and Banerjee, A. (1997). DSC, FTIR and TGA

studies of vinyl acetate-2-ethylhexyl acrylate copolymer. Journal of Applied

Polymer Science. 65, 2075-2080.

Pang, Y.X., and Bao, X. (2003). Influence of temperature, ripening time and

calcinations on the morphology and crystallinity of hydroxyapatite

nanoparticles. Journal of European Ceramic Society. 23, 1697-1704.

Pasupuleti, S., and Madras, G. (2011). Synthesis and degradation of sorbitol-based

polymers. Journal of Applied Polymer Science. 121, 2861-2869.

Petricca, S.E., Marra, K.G., Kumta, P.N. (2006). Chemical synthesis of poly(lactic-

co-glycolic acid)/ hydroxyapatite composites for orthopaedic applications.

Biomaterials. 2, 277-286.

Qiu, H., Yang, J., Kodali, P., Koh, J., A.A, G. (2006). A citric acid- based

hydroxyapatite composite for orthopedic implants. Biomaterials. 27, 5845-

5854.

Serrano, M.C., Chung, E.J., and Ameer, G.A. (2010). Advances and applications of

biodegradable elastomers in regenerative medicine. Advance Functional

Materials. 20, 192-208.

Vaidya, U.R., and Nadkarni, M. (1987). Unsaturated polyester from PET waste:

Kinetics of polycondensation. Journal of Applied Polymer Science. 34, 235-

245.

Velazco.C, L.1., Nonell, J.M., Valdes, S.S., and Valle, F.R. (2009). Morphology and

osteogenetic characteristics of polyamide/ nanohydroxyapatite

biocomposites. Polymer Bulletin. 62, 99-110.

Wang, Y., A. A, G., Sheppard, B.J., and Langer, R. (2002). A tough biodegradable

elastomers. Biomaterials. 20, 602-606.

Weng.H, T., Wahit, M.U., Kadir.A, M.R., and Wong, T.W. (2013). Mechanical and

thermal properties of biodegradable hydroxyapatite/ poly(sorbitol malate)

composites. Journal of Science and Technology. 35 (1), 57-61.

Wu, Y., Shi, R., Chen, D., Zhang, L., and Tian, W. (2010). Nanosilica filled

poly(glycerol-sebacate-citrate) elastomers with improved mechanical

properties, adjustable degradability, and better biocompatibility. Applied

polymer science. 123, 1612-1620.

Xie, R., Fu, H., Ji, X., Yao, J. (2002). Characterization of the size- dependent optical

properties of p- terphenyl nanocrystals. Photochemistry and Photobiology.

147,31-37

Xu, W., Liang, G., Wang, W., Tang, S., He, P., and Pan, W.P. (2003). PP-PP-g-

MAH Nanocomposites. I. Intercalation. Behavior and Microstructure. 88,

3225-3231.