Synthesis and characterization of non shrinking nanocomposites for dental applications 2

1.2 Research Objectives With the development of dental monomers with reduced polymerization shrinkage and stress becoming a major focus of dental biomaterials research, we aim to develo

Despite its excellent clinical record, dental amalgam has several disadvantages These include the need for removal of sound tooth structure for retention, inability

to bond to tooth surface and susceptibility to corrosion The use of amalgam has also been subjected to more and more controversies due to the fear of mercury toxicity During the placement and removal of amalgam restorations, small amounts of mercury vapors are released leading to health and environmental concerns.6,7 Although dental healthcare workers generally do not show signs of mercury toxicity, the mercury body burden of dental personnel was found to be slightly higher than the non-exposed group Dental healthcare workers with high occupational exposure to mercury vapors were also found to be less fertile than unexposed groups.6 While issues of mercury toxicity by amalgam restorations are still being debated, the Swedish government has proposed for the elimination of amalgam as a dental restorative material since 1997,8 due to environmental concerns especially the waste management of amalgam.9

While the risks associated with mercury in dental amalgam are debatable,

it is interesting to note that the use of amalgam as a restorative material has declined rapidly in the last half-decade due to aesthetic reasons Amalgam is aesthetically unattractive, metallic in color and does not resemble the physical characteristics of tooth structure The release of metallic ions from the amalgam restoration can also discolor the neighboring tooth structure.10 Thus, with increase

in aesthetic demands by patients and clinicians, tooth-colored composite resin restorations were viewed as an attractive alternative to amalgam restorations

Dental composites which consists of monomer resins, ceramic fillers, coupling agents and initiator/catalyst systems for polymerization were first developed in the early 1960s11,12 as aesthetic alternatives for tooth restorations One of the major improvements in resin-based composite has resulted from increased filler loading along with variation in distribution, size, shape and composition This modification to the filler component brings improvements in wear resistance, color stability, strength, radiopacity and degree of conversion of dental composites and thus the overall improvement in clinical performance of these materials However, despite vast improvements in composite materials and their mechanical properties, present day composite resins still have shortcomings limiting their application Inadequate resistance to wear (loss of anatomic form) under masticatory attrition, fracture of the restorations, discoloration, marginal adaptation, secondary caries and marginal leakage due to polymerization shrinkage are some of the factors limiting the longevity of composite resins.4,13-16

Commercial dental composites exhibit 2-14 % volumetric shrinkage during the polymerization process.17-20 When composites shrink, stresses are generated at the composite/tooth interface These shrinkage stresses can cause marginal openings if the bonding system is unable to withstand the polymerization forces and thus lead to leakage and ultimately caries Despite the dramatic improvements in the formulation of newer generation bonding agents with enhanced marginal adaptation and bond strengths, a perfect marginal seal is still not achievable Clinical studies carried out for resin-based composite restorations for Class I and II cavities for a period of 3 to 6 years have also shown that secondary and/or recurrent caries were the main reasons for restoration failure4,21,22 and polymerization shrinkage has been cited as one of the most significant factors influencing the seal between tooth structure and polymer-based restorative materials Thus, the major and most significant drawback of composite-based resins is the shrinkage during the polymerization process This remains one of the greatest challenges in composite resin technology and the ultimate solution to polymerization shrinkage is to develop “non-shrinking” resins

1.2 Research Objectives

With the development of dental monomers with reduced polymerization shrinkage and stress becoming a major focus of dental biomaterials research, we aim to develop novel low/non-shrinking nanocomposites based on polyhedral silsesquioxanes (SSQ) for dental applications The objectives of this research were to:

(a) Design and develop low/non-shrinking SSQ-based nanocomposites with methacrylate and epoxy functional groups

(b) Synthesize and characterize the SSQ neat resins for their chemical, thermal, physical and mechanical properties

(c) Study the effects of mixing SSQ-based nanocomposites with existing dental monomers in different compositions for improvement in physico-mechanical properties

(d) Develop and characterize promising experimental nanocomposites by mixing SSQ-based nanocomposites and/or dental monomers with ceramic fillers

C HAPTER 2

Literature Review

2.1 Chemically Cured Composite Resins

Chemically cured (self or auto cured) dental composite resins were first developed in the late 1950s They were found to be insoluble, aesthetic, insensitive to dehydration, inexpensive and easy to manipulate Curing of the composites was initiated by mixing two pastes that brought together the initiator,

dibenzoyl peroxide, and the activator, tertiary amines such as hydroxyethyl)-p-toluidine (DHEPT) or N,N-dimethy-p-toluidine (DMPT), in order

N,N-di-(2-to initiate the polymerization reaction (Figure 2.1).23 Curing of the composite ensures uniform polymerization throughout the bulk of restorative material However, the materials were found to be only partially successful and are not commonly used today due to issues such as poor activator systems, poor wear resistance, high polymerization shrinkage and mis-matched coefficient of thermal expansion These adverse physical properties prevented chemically cured composites from being the material of choice for clinicians The lack of wear resistance prevented them from preserving restoration contour in areas subject to abrasion or attrition They were not meant for use in high-stress areas due to low strength of the material which tended to flow under load Their high polymerization shrinkage and coefficient of thermal expansion led to microleakage and discoloration at the margins due to percolation.24 Clinicians were also constrained by the polymerization setting time when placing and

shaping the restoration In addition, clinical studies showed that self-cured composites undergo more darkening than photo-cured composites over time.25Thus, the aforementioned limitations of self-cured composites have led to the development of light-activated composites that offer the advantages of controlled working time and the elimination of time consuming mixing procedures that often introduce unwanted porosities to the restorations When compared to the chemically cured composites, light-activated composites demonstrated greater strength, fracture toughness, better shade selection, color stability and higher surface polymerization conversion rates

O O

DHEPT

+

N

OH HO

2.2 Light-activated Composite Resins

The beginning of modern restorative dentistry was marked by the

methacryloxypropoxy)phenyl]-propane)/ inorganic particle formulations in the early 1960s (Figure 2.2).11,12 The introduction of this composite-based resin technology to restorative dentistry was one of the most significant contributions to dentistry in the last century Applications for this new polymer include anterior and posterior composite resin restorations, indirect inlays/onlays, pit and fissure sealants and more wear-resistant denture teeth.26

O O

Figure 2.2 Chemical structure of Bis-GMA monomers

Composite materials refer to a mixture of two or more distinctly different materials with properties that are superior or intermediate to those of the individual constituents Dental composites are complex, tooth-colored filling materials composed of synthetic polymers, inorganic particulate fillers, initiators and activators that promote light-activated polymerization of the organic matrix to form cross-linked polymer networks, and silane coupling agents which bond the reinforcing fillers to the polymer matrix Further additives such as stabilizers and pigments are also included Each component of the composite is crucial for the success of the final dental restoration.23

Light-activated composite resins undergo free radical polymerization by irradiation with blue light in the wavelength range of 410 - 500 nm Light in this region is most effectively absorbed by an α-diketone photoinitiator, usually

camphorquinone (CQ), and creates an excited state that reacts with an amine

reducing agent such as N,N-dimethylaminoethyl methacrylate (DMAEMA) or ethyl p-dimethylaminobenzoate (DMAB) to produce free radicals that initiate the

cross-linking polymerization (Figure 2.3).27,28 The absorption spectrum of CQ lies

in the 450 - 500 nm wavelength range, with peak absorption at 470 nm.29,30

Figure 2.3 Light activation mechanism

2.3 Organic Matrix

The current organic matrix used in dental composites is based on methacrylate chemistry with cross-linking dimethacrylate being most universal Approximately eighty to ninety percent of commercial dental composites use Bis-GMA monomer as their organic matrix.31,32 Other base monomers used in present commercial composites include triethyleneglycol dimethacrylate (TEGDMA), urethane dimethacrylate (UDMA), ethoxylated bisphenol-A-dimethacrylate (Bis-EMA), decanediol dimethacrylate (D3MA) bis(methacryloyloxymethyl) tricyclodecane and urethanetetramethacrylate (UTMA) The chemical structures

The most commonly used organic matrix, Bis-GMA has a very high viscosity due to the hydrogen bonding interactions that occur between the hydroxyl groups on the monomer molecules Therefore, Bis-GMA must be diluted with more fluid monomers to provide the proper viscosity for use in dental composites.23 TEGDMA which is less viscous and has excellent copolymerization characteristics is frequently used as the diluent monomer for UDMA and BisGMA-based composites to produce a fluid resin that can be maximally filled with inorganic filler particles Optimal properties are produced when TEGDMA is used in a 1:1 ratio with Bis-GMA.33 Some other diluents include ethylene- and hexamethylene-glycoldimethacrylate and benzyl methacrylate.34 TEGDMA has also been replaced with UDMA and BisEMA in several products to reduce shrinkage, aging and environmental effects.35 UDMA and BisEMA have higher molecular weights and fewer double bonds per unit of weight when compared to TEGDMA that generally results in lower shrinkage

O TEGDMA

O

O O

O UDMA

D 3 MA

Figure 2.4 Chemical structures of common base monomers used in dental

composites

2.4 Inorganic Fillers

The use of resin matrix by itself is not a suitable restorative material as it demonstrates unsuitable physico-mechanical properties Addition of inorganic fillers is often needed to strengthen mechanical properties, provide radiopacity and reduce thermal expansion, polymerization shrinkage and water sorption In general, the physico-mechanical properties of composites are improved in direct relationship to the amount of filler added Fine powders of crystalline or non-crystalline silica or silicates are normally used as fillers The type and size of filler material used has been employed as a basis for classification of modern dental composites (Table 2.1).36

size and filler-loading improved the wear resistance of the early composite resins Modern composite systems contain fillers such as quartz, colloidal silica and silica glass containing barium, strontium and zirconium These fillers increase strength and modulus of elasticity and reduce the polymerization shrinkage, the coefficient

of thermal expansion and water sorption.37 The type of fillers and improvements related to nanofilled composites will be discussed in section 2.8

2.5 Silane Coupling Agent

Formation of a strong covalent bond between the inorganic filler particles and organic matrix is essential for obtaining good mechanical properties in dental composites.38 Failure of the filler-matrix interface will result in fracture and subsequent disintegration of the composite as a result of uneven distribution of stresses developed under load throughout the material Bonding of these two phases is achieved by coating the fillers with a silane coupling agent that has functional groups to chemically link the filler and the matrix A typical coupling agent used is γ-methacryloxypropyltrimethoxysilane (γ-MPTS) (Figure 2.5) One end of the molecules can be bonded to the hydroxyl groups of the silica particles with the other end capable of copolymerizing into the polymer matrix

OCH3OCH3

OCH3O

Figure 2.5 Structure of MPTS, a typical silane coupling agent used in dental

composites

2.6 Limitations of Current Dental Composites

The development of light-activated composite materials in the 1970s heralded a period of rapid progress in the field of tooth-colored restorations One

of the most obvious changes in dental practice during the 1970’s was the way in which composites became the most popular material for aesthetic anterior restorations.39 However, despite vast improvements in composite materials, present day composite resins still have shortcomings limiting their application As mentioned in Chapter 1, inadequate resistance to wear under masticatory attrition, fracture of the restorations, incomplete conversion and cross-linking, undesirable water sorption, marginal adaptation, secondary caries and marginal leakage due to polymerization shrinkage are often cited as being the main problems of composite resins.13,15,40

2.6.1 Polymerization shrinkage

Despite improvements in components and characteristics of composite materials, polymerization shrinkage still remains a clinically significant problem.41-44 Dental composites exhibit the inherent problem of 2-14 % volumetric shrinkage during polymerization processes17,19,45,46 and are affected by factors such as constituents of the resin-based composite material, configuration

of the cavity preparation, spectral distribution and power of the visible curing unit, and clinicians technique.47 The total shrinkage of composite materials can be divided into pre-gel and post-gel phases During the pre-gel polymerization, the composite is able to flow and stresses within the structure are relieved.48 After gelation, viscosity increases significantly and stresses due to shrinkage cannot be

light-surrounding tooth structure and composite tooth bond49 that may lead to bond failure, microleakage, post-operative sensitivity and recurrent caries These stresses could also result in deformation of the surrounding tooth structure if the composite-tooth bond is strong, predisposing the tooth to fracture.50

As previously mentioned, the stress associated with the curing contraction

is one of the most significant problems for current materials, as it adversely affects the seal at the cavosurface margin and causes occurrence of secondary caries.51When bonding of the adhesive to the tooth structure is inadequate, composite shrinks and pulls away from the cavity walls, forming an opening This opening at the restoration margins causes clinical problems such as microleakage, straining, sensitivity, and/or recurrent caries However, when the bonding to tooth structure

is strong enough, polymerization stress is applied to the tooth as composites shrink This causes fractured cusps, movement of cusps, and/or postoperative sensitivity.47

While Bis-GMA, TEGDMA and UDMA composite resin systems exhibit significant volume shrinkage on curing48,52,53, water sorption by polymer network contributes to stress reduction However, its effect is minimized as water uptake

by composite resins takes place at a much slower rate, requiring hours to reach saturation.54 In addition, water sorption has also been found to weaken the resin matrix and to cause filler/matrix debonding and hydrolytic degradation of the fillers with a subsequent reduction in mechanical properties and wear resistance.55-

57 The effect of water sorption can be reduced by the use of more hydrophobic

monomers, such as BisEMA, which do not contain unreacted hydroxyl groups on the main polymer chain.34

Besides, differences in monomer chemistry, various degrees of final polymerization, filler types and filler concentrations, the amount of stress generated is also dependent on the configuration of the cavity preparation Configuration factor, commonly known as the C-factor, is defined as the ratio of the bounded area of the restoration to the unbounded area.49 The higher the C-factor, the greater the stress on the bonded surfaces.58 Since composite flow is more likely to occur from the free surfaces of the specimen, a higher proportion of free composite surface would correspond to a smaller restriction to shrinkage, thereby reducing stress When the free surface is reduced, the ability to flow and compensate for shrinkage is restricted by the bonded surfaces thus, increasing stress As cavity preparations present a much more complex geometry with heterogeneous stress distribution59, the application of the C-factor concept to clinical practice must be performed carefully

The effect of post-gel shrinkage and stress can also be minimized by clinical techniques such as incremental layering of the composite during placement60 and application of a low elastic modulus liner between the tooth and shrinking composite restorative.61 A recent method to minimize polymerization shrinkage without affecting the degree of conversion in light-activated composites

is to reduce the viscosity during setting by means of controlled polymerization This can be achieved by application of short pulses of energy (pulse activation),

light followed by a final cure at high intensity (soft-start techniques) While some studies have shown that these polymerization modes resulted in lower shrinkage, smaller marginal gap, increased marginal integrity and improved material properties62-64, others have found no significant difference in shrinkage when compared to continuous cure modes.65-68 Thus, one of the greatest challenges and the ultimate solution to polymerization shrinkage is to develop expanding, low-shrinking or non-shrinking resins

2.7 New Resin Technology

While shrinkage stresses can be reduced by increasing filler loading, the ultimate solution to polymerization shrinkage is to develop “non-shrinking” resins Although earlier efforts to synthesize such resins were not successful, several developments in the last decade are more encouraging

2.7.1 Ring-opening Monomers

In 1992, Stansbury69 synthesized spiro-orthocarbonate monomers (SOCs) which expand during polymerization through a double-ring opening process These monomers contain methylene groups capable of free radical polymerization, making them useful as additives to dimethacrylates (Figure 2.6) However, the expanding SOCs synthesized were found to have low reactivity for free radical additions In order to enhance the reactivity of SOC monomers, SOC-substituted methacrylates70 were synthesized (Figure 2.7) These monomers resulted in nearly complete ring-opening of the SOC when polymerized in dilute solutions However,

less ring-opening was obtained when the resin was cured in bulk and the composites had about 1 % shrinkage

O O

O

O O

O

O O

O

Figure 2.7 Chemical structures of SOC-substituted methacrylate

The synthesis of six-membered SOCs co-polymerized with epoxy functional groups via cationic UV photo-initiation has also been reported.71,72 This alicyclic SOCs (trans/trans-2,3,8,9-di(tetramethylene)-1,5,7,11-tetraoxaspiro[5.5] undecane) (Figure 2.8) containing four rings attached to a central spiro carbon was polymerized in the presence of cationic initiator (4-octyloxyphenyl)-phenyliodonium hexafluoroantimonate, with chlorothioxanthone as a sensitizer The neat SOC monomers resulted in an expansion of 3.5 vol% The mixing of 5%

of the SOC monomers in an epoxy base produced a resin with substantial tensile strength and modulus, acceptable water sorption and solubility, and a slight expansion Increased concentrations of the SOC produced greater expansion and slightly stronger polymers, but high water sorption and solubility due to incomplete reaction of the SOC While results of these studies are promising, no

commercial materials are available to date This may be due to the high cost of the monomer

O

O

O O

Figure 2.8 Cationic polymerizable SOC

Miyazaki et al.73 have also reported on the development of acrylate and methacrylate containing spiro ortho esthers that were capable of being polymerized by heat, ionic and free radical initiators Though all common methods of curing were possible, the resultant polymers were weak and the reduction in shrinkage was not clinically significant

Besides SOCs, cationic photopolymerizable epoxy monomers, in particular cross-linking cycloaliphatic epoxy compounds, were of great interest These epoxy resins demonstrate significantly lower shrinkage than dental methacrylate resins and were reactive enough to be cured by cationic photopolymerization in an acceptable time frame using visible light-curing units One example in the application of this type of epoxy resins is that of epoxy-polyol mixtures While water sorption for these new resins was found to be slightly higher than that of traditional dimethacrylate, owing to the hydrophilic nature of the polyols, polymerization shrinkage was found to be significantly lower with comparable strength and stiffness.74 Recent work from 3M has also seen an experimental composite based on a mixture of two oxirane monomers and a small

amount of polyol (pTHF) (Figure 2.9) set by a cationic-initiated, light-activated reaction.75 This composite resulted in a volumetric shrinkage of 1.6% at 24 hours and was found to be significantly less than that of a conventional posterior composite, Z250.76

O O

O O

H O

O

O

O H

Figure 2.9 Chemical structures of cycloaliphatic diepoxide and polyol

In addition to epoxy resins, ring opening monomers such as oxetanes77,78, cyclic acetals79,80, cyclic allyl sulfides81 and vinylcyclopropanes82,83 have also been evaluated for dental applications However, none of them were found to be promising While oxetanes demonstrated a higher basicity with polymerization reactivity substantially affected by the type of atmosphere used78, cyclic acetals, cyclic allyl sulfides and vinylcyclopropanes compounds were found to be either unstable, have low reactivity, exhibited glass transition temperature (Tg) that were unacceptable for dental applications or resulted in polymers that have high flexibility

2.7.2 Liquid Crystalline Monomers

As the search for low-shrinking polymers continue, liquid crystalline or

usefulness as low-shrinking monomers While these pre-ordered monomers have the advantages of low viscosity, high degree of conversion and low shrinkage properties when compared to that of their corresponding linear monomers, they were found to melt at temperatures higher than 80 oC, resulting in complicated curing conditions In order to overcome this problem, several new liquid crystalline dimethacrylates84-86 (Figure 2.10) and/or branched liquid crystalline bismethacrylates87,88 (Figure 2.11) monomers with polymerization shrinkage ranging from 1.3 – 2.5 vol% have also been synthesized The syntheses of these monomers with a decrease in transformation temperature were achieved by modifying the spacer length, varying the mesogenic group and introducing suitable substituents in the mesogenic group While these monomers have the potential to be used as matrix monomers for dental composites due to their low polymerization shrinkage, low viscosity and high monomer conversion, they were expensive to synthesize and have low mechanical properties as a result of the more flexible polymer network

O C

O

O (CH2)6 O O

C O O

O

OR

O

ORO

Figure 2.11 Branched liquid crystalline bismethacrylates

2.7.3 Branched and Dendritic Monomers

Besides development in liquid crystalline monomers, highly branched liquid crystalline89-92 and dendritic monomers93,94 have also been synthesized and evaluated for dental composites These monomers were found to have the advantages of low polymerization shrinkage, viscosity and can be incorporated into formed polymer network efficiently However, due to their high flexibility of the formed polymer networks, these monomers often result in poor mechanical properties Thus, for successful application in dentistry, these monomers must produce networks with improved mechanical properties

non-2.7.4 Ormocers

Ormocers (organically modified ceramics), which refers to an organic hybrid dental materials is another type of dental materials developed with the aim of reducing polymerization shrinkage, improving marginal adaptation, abrasion resistance and biocompatibility The ormocers which have an inorganic backbone based on SiO2 are functionalized with polymerizable organic units such

inorganic-functionalized with a polymerizable group, followed by hydrolysis and condensation which led to an oligomeric Si-O-Si nanostructure (Figure 2.12).95However, due to its high viscosity, a diluent, TEGDMA, is often needed Despite comparable marginal adaptation, a recent study conducted on low shrinkage composites showed that a considerable amount of polymerization shrinkage is still present with this class of materials.15

Si OSi OSi R O

O

O

O R

O O O

O O

Figure 2.12 Synthesis of SiO2 nanostructures

Although these polymers are promising, problems balancing mechanical properties, water sorption, solubility, curing times and expansion still exist Recent advances of dental composites for reduced shrinkage with good mechanical properties and enhanced clinical performances have been made in the area of nanotechnology for the development of dental nanocomposites

2.8 Nanotechnology with Dental Composites

Nanotechnology, also known as nanoscience or molecular engineering, is defined as the creation of functional materials and structures with a characteristic dimension in the range of 0.1-100 nanometers by different physical or chemical techniques.96 This new technology that has become an important discipline in science and technology over the past ten years has shown promise in potential

applications areas such as aerospace, computers, telecommunications, microelectronics, biomedical, dental adhesives and dental composites This technology has also allowed for tougher, lighter, uncontaminated and more precise materials to be developed These great advances in nanotechnology have also resulted in the development of several dental nanocomposites with enhanced properties In composite resin technology, particle size and concentration within the matrix is responsible for the polishability, wear and fracture resistance

Dental filler particles are divided into groups according to their size as macrofiller, midifiller, minifiller and microfiller while megafill composites refer

to the addition of large glass beta-quartz inserts for protection against wear (Table 2.1) Macrofill composites, involved milling of large crystalline quartz and various borosilicate or lithium aluminosilicate glasses into various particle sizes ranging from 10 to 100 μm, and are not commonly used today due to esthetic concerns.97 These macrofillers which are hard and more resistant to wear when compared to the polymer matrix resulted in rough and less enamel-like restoration during abrasion

Microfill composites, which contain amorphous silica with an average particle size of 0.04 μm and a range of 0.01 to 0.1 μm, were developed to overcome polishing and esthetic requirements on the anterior restorations However, the large surface area of microfillers, lead to high viscosity formulations that are unusable and are the least highly filled composites.36 The lower concentration of fillers thus results in poorer mechanical properties such as lower

of material fractures were also observed in clinical trials when microfilled composites are placed in high stress areas.101,102 Based on many studies reported

on the correlation between mechanical properties and filler volume103, the current trend of composites is towards minimizing filler size and maximizing filler loading in an attempt to satisfy all the requirements for dental composites As there are currently no composite materials available to satisfy both the functional needs of a posterior Class I and II restoration and the superior esthetic requirements for anterior restorations104, the development of nanofillers and finally nanocomposites may be the solution

Nanofillers, which can be prepared by various techniques such as flame pyrolysis, flame spray pyrolysis and sol-gel processes, have particle sizes smaller than microfillers The extremely small filler particles have dimensions below the wavelengths of visible light and resulted in an inability to scatter or absorb visible light Thus nanofillers are virtually invisible and offer the advantage of optical properties improvement.105 In addition, due to small particle sizes, nanofillers are also capable of increasing the overall filler level by fitting into spaces between other particles in a composite Nanofillers theoretically should allow an overall filler level of 90-95% by weight This increase in filler level will also significantly reduce the effect of polymerization shrinkage and dramatically improve physical properties.36 In addition, composites containing nanofillers resulted in smoother surfaces with their ease of polishability106, increased abrasion resistance and surface hardness.107

The recent introduction of dental nanocomposites requires the effort of incorporating nanotechnology into the direct composite resin materials Filtek Supreme (3M ESPE, St Paul, MN) is one such example This advanced restorative system makes use of a synthetic chemical process to develop building blocks on a molecular scale The nanocomposite is composed of nanomeric particles and nanoclusters (Figure 2.13).105 Nanomers are monodisperse non-agglomerated and non-aggregated silica particles of 20-75 nm in dimension Nanocluster fillers are loosely bound agglomerates of nano-sized particles The agglomerates act as an individual component that allow for higher filler loading

Figure 2.13 Transmission electron micrographs of a hybrid, nanomer and

nanocluster (Courtesy of 3M ESPE)

Several research studies have also demonstrated that nanofilled composites have the capability of achieving a smoother surface with high translucency, high polish and polish retention comparable to those of microfills while maintaining physical properties and wear resistance equivalent to those of several hybrid composites.105,108 Mechanical properties such as fracture resistance, compressive and diametral strengths of the nanocomposite were found to be equivalent or

Davis109 has also maintained that the nanocomposite (Filtek Supreme) used for restoration has exhibited excellent handling properties when compared to other composites

Premise (Kerr/Sybron, Orange, CA), has developed a new approach to increase ceramic loadings using a distribution of trimodal particle sizes This trimodal approach was realized by integrating non-agglomerated discrete silica nanoparticles of 20 nm in dimension, prepolymerized filler (PPF) of 30-50 μm and barium glass filler of 0.4 μm in average size (proprietary Point 4 filler technology) into a resin matrix The silica nanofillers together with PPF and barium glass fillers allow for increased filler loading of 69% by volume and/or 84% by weight These discrete unassociated nanoparticles that are well dispersed in the matrix on

a nanoscale level allow for reduced viscosity in the resin matrix and thus resulted

in increased hardness, abrasion resistance, fracture resistance, improved polishability and reduced polymerization shrinkage and shrinkage stress.110-112

Another area of special interest with intense research and development has been in the area of polymerizable silica organosols These silica organosols contained discrete, non-agglomerated nanoparticles that are capable of being modified by organic silanes or other organic molecules Organosols can be prepared by Stöber’s method (Figure 2.14), which is a sol-gel process using alkoxysilanes as precursors113,114 followed by solvent exchange for introducing a polymerizable particle periphery.113,115,116

Si(OR)4 + Si(OH)4 + 4 ROH

SiO2 + 2 H2O Si(OH)4

NH3ROH

R = alkyl 4H2O

Figure 2.14 The Stöber process

Nanoparticles synthesized by the Stöber process have a distinct spherical shape with narrow size distribution106 that is useful for dental applications The monodispersed nanoparticles in reactive resins enhanced the mechanical properties, processability, increased filler loadings and improved transparency of the nanocomposite materials Other nanoparticles such as silica-zirconia106,117 and ZrO2118have also been synthesized to improve radiopacity and wear resistance of dental materials

Besides advances made in filler technology, dental matrices have also been another area of intensive research In the field of nanotechnology, inorganic-organic hybrid materials119-124 have been identified as an attractive area for the development of matrices for dental composites Inorganic-organic hybrid materials were synthesized using sol-gel processing techniques120,121 that combine organic compounds such as oligomers or polymers and inorganic oxides at the nano or molecular level with metal alkoxides as molecular precursors The hybrid materials are capable of achieving new properties by having different combinations and compositions of molecules Properties such as mechanical, marginal adaptation, wear resistance, biocompatibility and polymerization shrinkage can be improved and enhanced by the addition of inorganic structure in

One example of hybrid materials synthesized for potential dental applications was PMMA-silica hybrids which involved a mixture of methacrylate and silica These hybrid materials can either be synthesized by group-transfer copolymerization and hydrosilylation125 or by free radical polymerization15,126 to obtain PMMA precursors, which are then hydrolyzed and co-condensed with tetraethyl orthosilicate (TEOS).124 It was found that with a 50% or more silica content in this hybrid material, properties such as thermal stability, bulk density, hardness, young modulus, yield and compressive strength increased rapidly.122,127However, significant strain hardening was observed as a result of increased yield stress when 32% or more silica filler was added Thus by varying the amount of PMMA-silica content, mechanical properties could be adjusted and have the potential of enhanced conventional composites with similar silica contents

As mentioned earlier in section 2.7.4, Ormocers is another nanostructured hybrid material that has been used in commercial dental composites These materials have methacrylate groups that are separated from the trialkoxysilane moiety by different spacer groups (Figure 2.15) The more rigid the spacer groups, the higher the modulus of elasticity The silanes undergo hydrolysis and condensation to produce fluid-like materials that are mixed with fillers to generate composites capable of photopolymerization However, as aforementioned, the major disadvantage of methacrylate functionalized silanes is still the high polymerization shrinkage.15

O N Si(OEt)3O

O O

O

HO O

Figure 2.15 Example of commercially available methacrylate silanes

Polyhedral Oligomeric Silsesquioxane (POSSTM) (RSiO1.5)x, with a diameter of 0.54 nm, is one other hybrid organic-inorganic nanocomposite material evaluated for dental applications POSSTM, which can be regarded as the smallest particle of silica, is generally obtained by hydrolysis and condensation of trialkoxy or trichlorosilanes With a unique well-defined structure, POSSTM is often used for the preparation of hybrid materials with well-defined structures.128

It can also be chemically functionalized and behave as a platform from which to synthesize organic/inorganic nanocomposites for use in a variety of applications such as performance materials and abrasion resistant coatings

Incorporation of POSSTM derivatives into polymeric materials can help to improve mechanical properties, increase thermal stability, oxidation resistance and surface hardening as well as to reduce flammability and viscosity during processing POSSTM monomers, which do not require significant changes in processing, are simply mixed and copolymerized by traditional methods They form true molecular dispersions when mixed into polymer formulations with no phase separation and hence represent a significant advantage over current filler technologies.129

In recent years, several POSSTM molecules have been synthesized and investigated for dental applications Mono-methacrylate functionalized POSSTM

(Figure 2.16) synthesized by Gao et al.130 have been evaluated and used for copolymerization with methacrylate monomers It was found that incorporation of

small amounts (5% w/w) of POSSTM molecules resulted in improved mechanical properties and reduced shrinkage The potential of using POSSTM-MA (methacryl-POSSTM cage mixture) (Figure 2.17) as a replacement for Bis-GMA has also been investigated.131 It was also found that a small percentage substitution (mass fraction of 10% or less) of Bis-GMA with POSSTM-MA improved flexural strength and Young’s modulus of composites but large percentage substitution (mass fraction of 25% or more) resulted in undesirable mechanical properties, lower degree of conversion and slower photopolymerization rate Liquid epoxy-functionalized cubes (Figure 2.18) were other POSSTM structures designed for single phase composites with potential application for dental restoratives This epoxy POSSTM containing up to 65% masked silica was capable of producing hard, scratch- and solvent-resistant materials when photochemically cured.132

O

Si

O

Si O

Si

O Si

O Si

O O

O O

Si O

O Si

O Si

O O

Si O O Si

O Si O

Siloxane dendrimers (Figure 2.19), which were based on cyclic siloxane cores with photo-polymerizable side groups, were another class of cross-linking monomers investigated.133,134 This group of material demonstrated increased hardness and reduced viscosity that allowed for high amount of filler loading Moreover, uncured monomers linked to the siloxane cannot easily be leached out into surrounding gum tissue Siloxane dendrimers were found to have applications

in area of restorative fillings, crowns, bridges or cast restorations

Si O

Si O Si O Si

O

O O

O

O

O

Figure 2.19 Siloxane dendrimers

Over the last few years, advances in nanotechnology for applications in dentistry have provided dental restorative materials with improved properties Through the development of nanocomposites, properties such as modulus of elasticity, surface hardness, polymerization shrinkage and filler loading were enhanced by the addition of nanofillers Polymerizable ormocers when used as an alternative for conventional dimethacrylate matrix monomers can also help to improve both the biocompatibility and wear resistance properties The use of organic-inorganic hybrid materials such as POSSTM have also allowed for variation in composition where dental fillers and monomers can be tailor-made Moreover, with the POSSTM nanostructure, development of true nanocomposites

in contrast to composites filled with nanofillers (for example Filtek Supreme) is possible However, the number of studies on their development and enhancement

in properties particularly polymerization shrinkage are still limited Their efficacy

as monomer matrix for dental restoratives has yet to be explored

C HAPTER 3

Research Programme

3.1 Research Overview

From the review in Chapter 2, it is apparent that polymerization shrinkage

of light-activated composites and its accompanying stress still remain a clinical concern in dentistry Although numerous monomers have been developed to overcome the problem of polymerization shrinkage, difficulties in balancing mechanical properties, reactivity, water sorption, solubility and expansion still exist As light-activated composite resins continue to advance, a solution to the polymerization shrinkage problem is the development of organic-inorganic hybrid materials using polyhedral silsesquioxane While polyhedral silsesquioxane monomers with their well-defined 3-dimensional nanostructures as reviewed in section 2.8 have shown great potential in minimizing polymerization shrinkage, the number of studies on their applications in dentistry is still limited and more studies are warranted

In this study, fully functionalized polyhedral silsesquioxane with various functional groups such as methacrylate and epoxy will be developed Their efficiency as low shrinking light-activated nanocomposites and their roles as copolymers will also be evaluated

Phase Two

Preparation of Low/Non-shrinking SSQ-based Nanocomposites

The objective of this phase was to design and develop low/non-shrinking SSQ-based nanocomposites Different SSQ-based monomers with functional groups such as methacrylate and epoxy were attached to the platform material in different equivalents and combinations The SSQ-based monomers with different functional groups were synthesized using Pt-catalyzed hydrosilylation reaction at elevated temperatures (i.e < 60 oC) under argon atmosphere (Figure 3.1) Synthetic techniques and conditions were also evaluated and optimized in this phase

Si H

O Si

H O

O Si O O

O O

O Si

O Si O Si

O Si

O

Si

O Si O

Si

O

Si O

O O

Si Si

R

R

R R R

R

O O

R =+

Hydrosilylation

Methacrylate for subsequent polymerization

Allyl to react with SSQ

" Pt "

Figure 3.1 Example of SSQ-based monomers synthesized using Pt-catalyzed

hydrosilylation reaction

Phase Three

Chemical Characterizations of Synthesized SSQ-based Monomers

This phase involved structural characterizations of the synthesized materials developed in Phase 2 The synthesized materials were subjected to different chemical analysis techniques such as FTIR (Fourier Transform Infrared Spectroscopy), 1H-NMR (Proton Nuclear Magnetic Resonance), 13C-NMR (Carbon Nuclear Magnetic Resonance), 29Si-NMR (Silicon Nuclear Magnetic Resonance), DSC (Differential Scanning Calorimetry), TGA (Thermal Gravimetric Analysis) and SEC (Size Exclusion Chromatography) to confirm monomer structure and purity

FTIR which involves molecular absorption of selected frequencies (energies) of infrared radiation was used to determine the structural information of

a molecule The absorptions of each type of bond are found only in certain small portions of the vibrational infrared region and a small range of absorption can be defined for each type of bond

While the FTIR reveals the types of functional groups present in a molecule, NMR provides information about the number of magnetically distinct atoms and is an important technique used for structural determination The number of each of the distinct types of hydrogen nuclei as well as information regarding the nature of the immediate environment of each atom can be determined by proton NMR On the other hand, carbon NMR is used to determine the number of nonequivalent carbons and to identify the types of carbon atoms (methyl, methylene, aromatic, carbonyl, and so on) that may be present in a compound It is used to provide direct information about the carbon skeleton of a molecule Both techniques are often used together to determine the structure of unknown compounds

TGA is used to examine the mass change of a sample as a function of temperature in the scanning mode or as a function of time in the isothermal mode

It is used to characterize the decomposition and thermal stability of materials under a variety of conditions and to examine the kinetics of the physicochemical processes occurring in sample The mass change characteristics of a material are strongly dependent on the experimental conditions employed DSC is used to investigate the thermal properties of a material For example, melting and glass transition temperatures, as well as the exotherm of reaction

SEC which is also known as GPC (Gel Permeation Chromatography), provides information about the hydrodynamic volume and concentration of chains

of varying length, according to the elution time, uses porous particles to separate molecules of different sizes and has been used to determine molecular weights and

molecular weight distributions of polymers Polymer molecules that are smaller than the pore sizes in the particles can enter the pores, and therefore they have longer path and longer transit time than larger molecules that cannot enter the pores Motion in and out of pores is governed by Brownian motion Thus the larger molecules elute earlier in the chromatograph, while molecules that entered the pores elute later By appropriate calibration, the chromatogram is converted to

a true molecular weight distribution curve, from which all pertinent averages are easily calculated The characterization of polymers, as regards to molecular weight averages and distribution is essential in order to predict the relationship between the molecular structure and polymer performance

% of both visible light initiators (camphorquinone, CQ) and activators

(N,N-dimethylaminoethyl methacrylate, DMAEMA) to the control and synthesized SSQ-based monomers Both the control and SSQ-based monomers were formulated with the same amount of initiators and activators for comparison purposes

Phase Five

Physico-mechanical Properties Characterizations

This phase focused on the characterization of the physico-mechanical properties Post-gel polymerization shrinkage of both control material and synthesized SSQ-based monomers was investigated by a strain-monitoring device using 2 mm strain gauges over a period of one hour Mechanical properties such

as hardness and modulus were determined using the depth-sensing microindentation techniques over a period of 7 days Hardness data was obtained

by dividing the peak load over the maximum projected contact area while modulus was calculated by the unloading contact stiffness analysis.135 With all factors standardized, the results obtained were compared against the control to determine their efficiency as low-shrink monomers Data obtained was subjected

to one-way ANOVA and Scheffe’s post-hoc tests at significance level of 0.05

Phase Six

Effects of SSQ-based Monomers as Copolymers

The objective of this phase was to study the effects of mixing SSQ-based nanocomposites with the control monomers in different compositions for improving the physico-mechanical properties The SSQ-based nanocomposites were added in 5, 10, 20 and 50 wt% with respect to the control monomers Physico-mechanical properties as stated in Phase 5 were also determined The results obtained were compared against the control to determine the copolymerizing effects of SSQ-based monomers for improvements in mechanical and polymerization shrinkage properties Data obtained was subjected to one-way ANOVA and Scheffe’s post-hoc tests at significance level of 0.05

Phase Seven

Experimental SSQ-based Nanocomposites

From the results evaluated in Phases 5 and 6, materials which displayed low-shrinking and suitable mechanical properties were chosen for the development of experimental nanocomposites In this phase, four promising materials were chosen and incorporated with 63 wt% of commercial fillers The physico-mechanical properties as stated in Phase 5 were determined for these experimental materials In addition, physical properties such as depth of cure and water sorption were also determined according to ISO 4049.136 The degree of conversion was also determined using Photo-DSC This technique is capable of providing kinetic data at elevated temperature under low intensity radiation and is useful for the characterization of photopolymers With all factors standardized, the results obtained were compared against commercial dental composites to evaluate their usefulness as dental restorative materials Data obtained was subjected to one-way ANOVA and Scheffe’s post-hoc tests at significance level of 0.05

Phase Eight

General Conclusions and Future Perspectives

In the final phase of the programme, the research conducted was summarized and reviewed Brief introduction to the synthesis of SSQ with expanding monomers, benzoxazines, was discussed General conclusions and recommendations for future work were also made

The term silsesquioxane originated from siloxane (silicon and oxygen compounds) and sesqui which refers to one and a half in Latin, are structures with

the empirical formulas (RSiO1.5)n where R is hydrogen, or organofunctional derivative of alkyl, alkylene, aryl, arylene groups, or an extensive range of organic groups and n = 6, 8, 10 or higher Structures of silsesquioxanes include random, ladder, cage and partial cage structures (Figure 4.1) and are generally produced by the hydrolysis and condensation of trialkoxy- or trichlorosilanes (Figure 4.2).137,138

With its many good properties such as high temperature stability, hardness, tensile strength and its relative ease of preparation, interest in silsesquioxanes has increased exponentially over the years.138 Silsesquioxanes have also found wide applications as gas separation membranes, binders for ceramics, carcinostatic drugs, water repellent and abrasion resistant film on paper, rubber, plastic, metal

and coatings on electrical, optical, photoresist devices, liquid crystal display elements, semiconductors and magnetic recording media.138

O Si O

Si O Si O Si

O SiO

O

O O

O Si

O Si

OSi

R R R R R R

R R

Si O Si O Si O Si R O O

O RO

R R

O O

Si R O

O

Si O

R ORandom Structure

O Si O Si

O SiO

Si Si OO Si

O SiO Si O

O R

R

R O

O R R

R R

O

O R Ladder Structure

Cage Structure

O Si O

Si O Si O

Si O O OH

O Si

O Si

OSi

R R R R R

R

R OH OH

Partial Cage Structure

Figure 4.1 Some common structures of silsesquioxane

Si O

Si O Si O Si

O SiO

O

O O

O Si

O Si

OSi

R R R R R R

R R