materials Article Hydrophobically Modified Isosorbide Dimethacrylates as a Bisphenol-A (BPA)-Free Dental Filling Material Bilal Marie 1,2, Raymond Clark 2, Tim Gillece 2, Seher Ozkan 2, Michael Jaffe 1 and Nuggehalli M. Ravindra 1,* 1 Interdisciplinary Program in Materials Science and Engineering, New Jersey Institute of Technology, Newark, NJ 07012, USA; [email protected] (B.M.); [email protected] (M.J.) 2 Ashland Specialty Ingredients, Bridgewater, NJ 08807, USA; [email protected] (R.C.); [email protected] (T.G.); [email protected] (S.O.) * Correspondence: [email protected] Abstract: A series of bio-based hydrophobically modified isosorbide dimethacrylates, with para-, meta-, and ortho- benzoate aromatic spacers (ISBGBMA), are synthesized, characterized, and evaluated as potential dental restorative resins. The new monomers, isosorbide 2,5-bis(4-glyceryloxybenzoate) dimethacrylate (ISB4GBMA), isosorbide 2,5-bis(3-glyceryloxybenzoate) dimethacrylate (ISB3GBMA), and isosorbide 2,5-bis(2-glyceryloxybenzoate) dimethacrylate (ISB2GBMA), are mixed with triethy- lene glycol dimethacrylate (TEGDMA) and photopolymerized. The resulting polymers are evaluated for the degree of monomeric conversion, polymerization shrinkage, water sorption, glass transition temperature, and flexural strength. Isosorbide glycerolate dimethacrylate (ISDGMA) is synthesized, and Bisphenol A glycerolate dimethacrylate (BisGMA) is prepared, and both are evaluated as a reference. Poly(ISBGBMA/TEGDMA) series shows lower water sorption (39–44 µg/mm3) over 3 3 Poly(ISDGMA/TEGDMA) (73 µg/mm ) but higher than Poly(BisGMA/TEGDMA) (26 µg/mm ). Flexural strength is higher for Poly(ISBGBMA/TEGDMA) series (37–45 MPa) over Poly(ISDGMA/ Citation: Marie, B.; Clark, R.; Gillece, TEGDMA) (10 MPa) and less than Poly(BisGMA/TEGDMA) (53 MPa) after immersion in phosphate- T.; Ozkan, S.; Jaffe, M.; Ravindra, N.M. buffered saline (DPBS) for 24 h. Poly(ISB2GBMA/TEGDMA) has the highest glass transition tem- ◦ Hydrophobically Modified Isosorbide perature at 85 C, and its monomeric mixture has the lowest viscosity at 0.62 Pa·s, among the Dimethacrylates as a Bisphenol-A (ISBGBMA/TEGDMA) polymers and monomer mixtures. Collectively, this data suggests that the (BPA)-Free Dental Filling Material. ortho ISBGBMA monomer is a potential bio-based, BPA-free replacement for BisGMA, and could be Materials 2021, 14, 2139. https:// the focus for future study. doi.org/10.3390/ma14092139 Keywords: isosorbide dimethacrylates; dental filling material; hydrophobic; bio-based; bisphenol-A Academic Editor: Javier Gil (BPA) Received: 21 March 2021 Accepted: 19 April 2021 Published: 22 April 2021 1. Introduction Publisher’s Note: MDPI stays neutral Dental amalgam and resin-based composites are commonly used dental filling materi- with regard to jurisdictional claims in als. The recent US-FDA epidemiological review of exposure to dental amalgam mercury published maps and institutional affil- did not find sufficient evidence correlating adverse health outcomes with exposure to den- iations. tal amalgam mercury [1]. However, the negative perception of amalgam, lower aesthetic appeal [2], and the Minamata convention to minimize mercury production and impact [3], are leading reasons that resin-based composites are preferred. Dental resin composites consist of a polymeric resin, filler particles, and a coupling agent. The polymeric resin is largely made up of hydrophobic dimethacrylates that Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. crosslink into a three-dimensional network. These polymeric networks should have a This article is an open access article high degree of monomeric conversion, low water uptake, low polymerization shrinkage, distributed under the terms and and good mechanical properties [4,5]. conditions of the Creative Commons The most common dental restorative dimethacrylate monomer is 2,2-bis [4-(2-hydroxy- Attribution (CC BY) license (https:// 3-methacryloyloxypropoxy)phenyl] propane (BisGMA). Its structure imparts a high poly- creativecommons.org/licenses/by/ meric modulus, low shrinkage, and strong adhesion to the tooth enamel [6–8]. It is highly 4.0/). viscous and is typically mixed with the dental diluent, triethylene glycol dimethacrylate Materials 2021, 14, 2139. https://doi.org/10.3390/ma14092139 https://www.mdpi.com/journal/materials Materials 2021, 14, x FOR PEER REVIEW 2 of 18 Materials 2021, 14, 2139 It is highly viscous and is typically mixed with the dental diluent, triethylene glycol2 of di- 17 methacrylate (TEGDMA). However, TEGDMA is reported to increase water sorption and polymerization shrinkage [9,10]. In contrast, 1,6-bis(2-methacryloxy-2-ethoxycarbonyla- (TEGDMA).mino)-2,4,4-trimethylhexane However, TEGDMA (UDMA) is reported is a urethane to increase dimethacrylate water sorption with and lower polymeriza- viscosity tionin comparison shrinkage to [9 ,BisGMA,10]. In contrast, and exhibits 1,6-bis(2-methacryloxy-2-ethoxycarbonylamino)-2,4,4- good durability and adhesion to the tooth enamel trimethylhexane[11,12]. (UDMA) is a urethane dimethacrylate with lower viscosity in comparison to BisGMA,Dimethacrylates and exhibits exhibit good excellent durability properties and adhesion in resin to the dental tooth restoration. enamel [11, 12However,]. dentalDimethacrylates dimethacrylate exhibit monomers, excellent and properties the resulting in resin degradation dental restoration. products, However, were demon- den- talstrated dimethacrylate to exhibit a monomers,cytotoxic and and genotoxic the resulting effect degradation [13,14]. Further, products, prior were investigations demonstrated sug- togest exhibit that aTEGDMA cytotoxic and genotoxicUDMA can effect induce [13,14 apoptosis]. Further, in prior dental investigations pulp [15,16]. suggest Trace thatamounts TEGDMA of Bisphenol and UDMA A (BPA), can induce a suspected apoptosis estrogen in dental mimic, pulp can [15 be,16 ].present Trace amountsin BisGMA of Bisphenoland elute into A (BPA), the oral a suspected environment estrogen [17,18]. mimic, Increased can be levels present of inBPA BisGMA exposure and have elute been into thelinked oral to environment various prenatal, [17,18 ].childhood, Increased and levels adult of BPA adverse exposure health have outcomes. been linked These to include, various prenatal,but are not childhood, limited andto, reduced adult adverse fertility, health altered outcomes. childhood These behavior include, and but areneurodevelop- not limited to,ment, reduced type-2-diabetes, fertility, altered cardiovascular childhood behaviordisorders, and inflammation, neurodevelopment, and altered type-2-diabetes, gene expres- cardiovascularsion [19]. Hence, disorders, there has inflammation, been a growing and inte alteredrest in gene developing expression safer [19 ].alternative Hence, there materi- has beenals. a growing interest in developing safer alternative materials. IsosorbideIsosorbide isis aa sugar-basedsugar-based molecule derived from starch and is classifiedclassified as “gener- allyally recognizedrecognized asas safe”.safe”. It isis mademade upup ofof twotwo ciscis-fused-fused tetrahydrofurantetrahydrofuran rings,rings, whichwhich areare nearlynearly planar,planar, and and contains contains two two hydroxyls hydroxyls at positions at positions 2 and 2 5,and as shown5, as shown in Figure in 1Figure[20,21 ].1 Isosorbide[20,21]. Isosorbide has found has potentialfound potential applications applications in the in biomedical the biomedical field, field, including including aspirin as- prodrugspirin prodrugs [22,23 ],[22,23], substrates substrates for human for human butyrylcholinesterase butyrylcholinesterase [24], tissue [24], engineering tissue engineer- scaf- foldsing scaffolds [25,26], and[25,26], dental and restorative dental restorative materials materials [27–30]. [27–30]. FigureFigure 1.1. Chemical structure ofof isosorbide.isosorbide. SomeSome of the the studies studies on on isosorbide isosorbide for for dent dentalal materials materials include include the synthesis the synthesis and eval- and evaluationuation of the of BisGMA the BisGMA analogue, analogue, 1,4:3,6-dianhydro- 1,4:3,6-dianhydro-D-sorbitolD-sorbitol 2,5-bis( 2,5-bis(2-hydroxy-3-2-hydroxy-3-meth- methacylolxypropoxy)acylolxypropoxy) (ISDGMA) (ISDGMA) as reported as reported by Ł byukaszczyk Łukaszczyk et al., et al.,and and Shin Shin and and coworkers cowork- ers[27,28]. [27,28 Duarte]. Duarte et al., et al.,have have studied studied the thesynthesis synthesis of an of isosorbide an isosorbide urethane urethane dimethacrylate dimethacry- late(IS-UDMA) (IS-UDMA) [29]. [ 29Vasifihasel]. Vasifihasel et al. et and al. andŁukaszczyk Łukaszczyk and andco-workers co-workers developed developed ethoxylated ethoxy- latedisosorbide isosorbide dimethacrylates dimethacrylates (ISETDMA) (ISETDMA) as a de asntal a dental diluent diluent [30,31]. [30 ,Jun31]. et Jun al. et developed al. devel- opedisosorbide isosorbide dimethacrylates dimethacrylates based based on isocyano on isocyanoethylethyl methacrylates methacrylates and evaluated and evaluated their their per- performanceformance as dental as dental sealants sealants [32]. [32 Kim]. Kim et al. et al.reported reported on onisosorbide isosorbide 2,5-bis(propoxy) 2,5-bis(propoxy) di- dimethacrylatemethacrylate (ISOPMA) (ISOPMA) and and evaluated evaluated it itas as a a dental dental resin resin composite in comparisoncomparison toto ISDGMAISDGMA [[33].33]. TheThe aim aim of of this this study study is to is synthesize to synthesize and investigate and investigate