Synthesis, characterization and evaluation of azobenzene nanogels for their antibacterial properties in adhesive dentistry.

The presence of cariogenic bacteria within the prepared tooth cavity at the adhesive resin-dentin interface is detrimental to the long-term stability and function of composite restorations. Here, we report the synthesis and incorporation of methacrylated azobenzene nanogels within bisphenol A-glycidyl methacrylate/hydroxyethyl methacrylate/ethanol (B/H/E) adhesive resins and evaluate their ability to reduce the bacterial invasion of cariogenic Streptococcus mutans biofilms while preserving the mechanical strength and structural integrity of the critical interfacial connection between the restoration and the tooth. The azobenzene nanogel, with a hydrodynamic radius of < 2 nm and a molecular weight of 12,000 Da, was polymerized within B/H/E adhesive formulations at concentrations of 0.5 wt.%, 1.5 wt.%, and 2.5 wt.%. While the double-bond conversion, cytocompatibility, water solubility, and sorption of the adhesive networks were comparable, azobenzene nanogel networks showed improved hydrophobicity with a ≥ 25° increase in water contact angle. The polymerized adhesive surfaces formulated with azobenzene nanogels showed a 66% reduction in bacterial biofilms relative to the control while maintaining the mechanical properties and micro-tensile bond strength of the adhesive networks. The increased hydrophobicity and antibacterial activity are promising indicators that azobenzene nanogel additives have the potential to increase the durability and longevity of adhesive resins.

Rational Design of Efficient Amine Reductant Initiators for Amine-Peroxide Redox Polymerization.

Amine-peroxide redox polymerization (APRP) has been highly prevalent in industrial and medical applications since the 1950s, yet the initiation mechanism of this radical polymerization process is poorly understood so that innovations in the field are largely empirically driven and incremental. Through a combination of computational prediction and experimental analysis, we elucidate the mechanism of this important redox reaction between amines and benzoyl peroxide for the ambient production of initiating radicals. Our calculations show that APRP proceeds through SN2 attack by the amine on the peroxide but that homolysis of the resulting intermediate is the rate-determining step. We demonstrate a correlation between the computationally predicted initiating rate and the experimentally measured polymerization rate with an R2 = 0.80. The new mechanistic understanding was then applied to computationally predict amine reductant initiators with faster initiating kinetics. This led to our discovery of N-(4-methoxyphenyl)pyrrolidine (MPP) as amine reductant, which we confirmed significantly outperforms current state-of-the-art tertiary aromatic amines by ∼20-fold, making it the most efficient amine-peroxide redox initiator to date. The application of amines with superior kinetics such as MPP in APRP could greatly accelerate existing industrial processes, facilitate new industrial manufacturing methods, and improve biocompatibility in biomedical applications conducted with reduced initiator concentrations yet higher overall efficiency.

Photo-responsive liposomes composed of spiropyran-containing triazole-phosphatidylcholine: investigation of merocyanine-stacking effects on liposome-fiber assembly-transition.

A spiropyran-containing triazole-phosphatidylcholine (SPTPC) was synthesized through a copper-catalyzed azide alkyne cyclo-addition (CuAAC) reaction. In water, SPTPCs self-assembled and a spontaneous spiropyran-to-merocyanine (SP-to-MC) isomerization occurred, resulting in coexistence of liposomes and fibers, and switching from the spiropyran (SP) to the merocyanine (MC) isomeric structure induced a reversible transition between these molecular assemblies. Study of the self-assembly of SPTPCs and photo-induced liposome-fiber assembly-transition revealed that the presence of MC enabled additional inter-membrane interaction during self-assembly and that the MC-stacking effect was the driving force for the assembly-transition. Exposure to UV light induced switching from SP to MC, where the planar structure of MC and the confinement of MC led to enhanced MC-stacking. The effect of MC-stacking was both advantageous and disadvantageous: MC-stacking perturbed the hydrophobic phase in the bilayer membrane and facilitated the liposome-to-fiber transition, otherwise the MC-stacking retarded switching of MC to SP, and caused an incomplete recovery of MC to SP during fiber-to-liposome recovery, thus a fatigue of SP was induced by MC-stacking during the liposome-to-fiber transition cycle. To decrease the intermolecular interactions and suppress MC-stacking, photo-inert triazole-phosphatidylcholine (TPC) was incorporated to prepare two-component TPC/SPTPC-liposomes, which exhibited better recovery kinetics. The photo-adaptive behavior of TPC/SPTPC-liposomes confirmed the disturbance of bilayer membranes by inter-membrane MC-stacking and the formation of MCTPC-enriched phases in the bilayer membrane.

Photopolymerizable nanogels as macromolecular precursors to covalently crosslinked water-based networks.

We present a strategy for directly and efficiently polymerizing aqueous dispersions of reactive nanogels into covalently crosslinked polymer networks with properties that are determined by the initial chemical and physical nanogel structure. This technique can extend the range of achievable properties and architectures for networks formed in solution, particularly in water where monomer selection for direct polymerization and the final network properties are quite limited. Nanogels were initially obtained from a solution polymerization of a hydrophilic monomethacrylate and either a hydrophilic PEG-based dimethacrylate or a more hydrophobic urethane dimethacrylate, which produced globular particles with diameters of 10-15 nm with remarkably low polydispersity in some cases. Networks derived from a single type of nanogel or a blend of nanogels with different chemistries when dispersed in water gelled within minutes when exposed to low intensity UV light. Modifying the nanogel structure changes both covalent and non-covalent secondary interactions in the crosslinked networks and reveals critical design criteria for the development of networks from highly internally branched, nanoscale prepolymer precursors.

Modification of linear prepolymers to tailor heterogeneous network formation through photo-initiated Polymerization-Induced Phase Separation.

Polymerization-induced phase separation (PIPS) was studied in ambient photopolymerizations of triethylene glycol dimethacrylate (TEGDMA) modified by poly(methyl methacrylate) (PMMA). The molecular weight of PMMA and the rate of network formation (through incident UV-irradiation) were varied to influence both the promotion of phase separation through increases in overall free energy, as well as the extent to which phase development occurs during polymerization through diffusion prior to network gelation. The overall free energy of the polymerizing system increases with PMMA molecular weight, such that PIPS is promoted thermodynamically at low loading levels (5 wt%) of a higher molecular weight PMMA (120 kDa), while a higher loading level (20 wt%) is needed to induce PIPS with lower PMMA molecular weight (11 kDa), and phase separation was not promoted at any loading level tested of the lowest molecular weight PMMA (1 kDa). Due to these differences in overall free energy, systems modified by PMMA (11 kDa) underwent phase separation via Nucleation and Growth, and systems modified by PMMA (120 kDa), followed the Spinodal Decomposition mechanism. Despite differences in phase structure, all materials form a continuous phase rich in TEGDMA homopolymer. At high irradiation intensity (Io=20mW/cm2), the rate of network formation prohibited significant phase separation, even when thermodynamically preferred. A staged curing approach, which utilizes low intensity irradiation (Io=300µW/cm2) for the first ~50% of reaction to allow phase separation via diffusion, followed by a high intensity flood-cure to achieve a high degree of conversion, was employed to form phase-separated networks with reduced polymerization stress yet equivalent final conversion and modulus.

Accessing photo-based morphological control in phase-separated, cross-linked networks through delayed gelation.

This work presents an approach to extend the period for phase separation, independent of temperature, in ambient phase-separating photopolymerizations based on the copolymerization of structurally similar mono- and di-vinyl monomers. Copolymer resins composed of triethylene glycol dimethacrylate (TEGDMA) and ethylene glycol methyl ether methacrylate (EGMEMA) were modified with a thermoplastic prepolymer, poly(butyl methacrylate). With increasing EGMEMA modification into the bulk TEGDMA resin, there is a decrease in the initial reaction rate, which increases the time for development of compositionally different phases prior to network gelation. The period between phase separation and gelation was probed through optical and rheological measurements, and it was extended from 22 s in a TEGDMA resin to 69 s in a TEGDMA:EGMEMA copolymer, allowing these materials to be processed under a wide range of UV-irradiation intensities (300 µW cm-2 - 100 mW cm-2), which provided an additional degree of control over the resulting phase separated domain size and morphology.

Effect of antioxidants on the dentin interface bond stability of adhesives exposed to hydrolytic degradation.

PURPOSE: This study assessed the effect of antioxidants vitamin C (Vit. C), vitamin E (Vit. E) and quercetin (Querc) on the dentin bonding performance, degree of conversion, and rate of polymerization of three commercial adhesive systems (Adper Single Bond 2 [SB], Clearfil SE Bond [CSE], Adper Easy Bond [EB]). MATERIALS AND METHODS: Human premolars were restored using antioxidant-doped adhesives. The samples were stored for 24 h in distilled water or 6 months under simulated pulpal pressure. Teeth were cut into sticks and the microtensile bond strength (µTBS) to dentin was tested in a universal testing machine. Qualitative nanoleakage analysis was performed from a central stick of each restored tooth. Degree of conversion and rate of polymerization of adhesive systems were evaluated in triplicate using real-time FT-IR. RESULTS: Although the inclusion of the antioxidants negatively affected the µTBS over 24 h, the antioxidant-doped adhesives maintained (SB-Vit. C, SB-Vit. E, CSE-Vit. C, EB-Querc) or increased (SB-Querc, CSE-Vit. E, CSE-Querc, EB-Vit. E, and EB-Vit. C) their µTBS during 6 months of storage. Only the µTBS of Adper Single Bond 2 dropped significantly after 6 months among the control groups. Slight changes in the nanoleakage pattern after aging were observed in all groups, except for the EB-control group, which showed a noteworthy increase in nanoleakage after 6 months, and for EB-Vit. C, which presented a remarkable decrease. A lower degree of conversion was obtained with all antioxidants in SB and EB, except for the EB-Vit. E group. Similar degrees of conversion were attained in control and experimental groups for CSE. The rate of polymerization was reduced in antioxidant-doped adhesives. CONCLUSION: The performance of antioxidants changed according to the adhesive system to which they were added, and antioxidant-doped adhesives appear to have a positive effect on the adhesive interface durability, since their bond strength obtained after 24 h was maintained or increased over time.

Visible-light organic photocatalysis for latent radical-initiated polymerization via 2e⁻/1H⁺ transfers: initiation with parallels to photosynthesis.

We report the latent production of free radicals from energy stored in a redox potential through a 2e(-)/1H(+) transfer process, analogous to energy harvesting in photosynthesis, using visible-light organic photoredox catalysis (photocatalysis) of methylene blue chromophore with a sacrificial sterically hindered amine reductant and an onium salt oxidant. This enables light-initiated free-radical polymerization to continue over extended time intervals (hours) in the dark after brief (seconds) low-intensity illumination and beyond the spatial reach of light by diffusion of the metastable leuco-methylene blue photoproduct. The present organic photoredox catalysis system functions via a 2e(-)/1H(+) shuttle mechanism, as opposed to the 1e(-) transfer process typical of organometallic-based and conventional organic multicomponent photoinitiator formulations. This prevents immediate formation of open-shell (radical) intermediates from the amine upon light absorption and enables the "storage" of light-energy without spontaneous initiation of the polymerization. Latent energy release and radical production are then controlled by the subsequent light-independent reaction (analogous to the Calvin cycle) between leuco-methylene blue and the onium salt oxidant that is responsible for regeneration of the organic methylene blue photocatalyst. This robust approach for photocatalysis-based energy harvesting and extended release in the dark enables temporally controlled redox initiation of polymer syntheses under low-intensity short exposure conditions and permits visible-light-mediated synthesis of polymers at least 1 order of magnitude thicker than achievable with conventional photoinitiated formulations and irradiation regimes.

Light-activated, in situ forming gel for sustained suprachoroidal delivery of bevacizumab.

A light-activated polycaprolactone dimethacrylate (PCM) and hydroxyethyl methacrylate (HEMA) based gel network was developed to sustain the release of stable, active bevacizumab (an anti-VEGF antibody used to treat choroidal neovascularization) and used to assess sustained ex vivo delivery in rabbit eyes and in vivo delivery in rat eyes following in situ gel formation in the suprachoroidal space. PCM was synthesized from polycaprolactone diol (PCD) and evaluated using NMR spectroscopy. PCM was used to cross-link HEMA in the presence of 365 nm UV light and 2,2-dimethoxy-2-phenylacetophenone (DMPA) as a photoinitiator. Bevacizumab was entrapped in the gel using three different cross-linking durations of 3, 7, and 10 min. In vitro release of bevacizumab in PBS pH 7.4 at 37 °C during a 4 month study was quantified using a VEGF-binding based ELISA. The stability of released bevacizumab was monitored by size exclusion chromatography (SEC) and circular dichroism. Alexa Fluor 488 dye conjugated bevacizumab mixed with polymers was injected suprachoroidally in rabbit eyes to study the effect of different cross-linking durations on the spread of the dye conjugated bevacizumab. In vivo delivery was assessed in Sprague-Dawley (SD) rats by injecting Alexa Fluor 488 dye conjugated bevacizumab mixed with polymers followed by cross-linking for 10 min. Spread in the rabbit eyes and in vivo delivery in rat eyes was monitored noninvasively using a fundus camera and Fluorotron Master. The formation of PCM was confirmed by the disappearance of hydroxyl peak in NMR spectra. A cross-linking duration of 10 min resulted in a burst release of 21% of bevacizumab. Other cross-linking durations had ≥62% burst release. Bevacizumab release from 10 min cross-linked gel was sustained for ∼4 months. Release samples contained ≥96.1% of bevacizumab in the monomeric form as observed in SEC chromatograms. Circular dichroism confirmed that secondary ß-sheet structure of bevacizumab was maintained after release from the gel. As the cross-linking duration was increased to 10 min, the gel/antibody was better confined at the injection site in excised rabbit eye suprachoroidal space. Delivery of Alexa Fluor 488 dye conjugated bevacizumab was sustained for at least 60 days in the suprachoroidal space of SD rats. PCM and HEMA gel sustained bevacizumab release for 4 months and maintained the stability and VEGF-binding activity of bevacizumab. Therefore, light-activated PCM and HEMA gel is suitable for in situ gel formation and sustained protein delivery in the suprachoroidal space.

A new approach to network heterogeneity: Polymerization Induced Phase Separation in photo-initiated, free-radical methacrylic systems.

Non-reactive, thermoplastic prepolymers (poly- methyl, ethyl and butyl methacrylate) were added to a model homopolymer matrix composed of triethylene glycol dimethacrylate (TEGDMA) to form heterogeneous networks via polymerization induced phase separation (PIPS). PIPS creates networks with distinct phase structure that can partially compensate for volumetric shrinkage during polymerization through localized internal volume expansion. This investigation utilizes purely photo-initiated, free-radical systems, broadening the scope of applications for PIPS since these processing conditions have not been studied previously.The introduction of prepolymer into TEGDMA monomer resulted in stable, homogeneous monomer formulations, most of which underwent PIPS upon photo-irradiation, creating heterogeneous networks. During polymerization the presence of prepolymer enhanced autoacceleration, allowing for a more extensive ambient cure of the material. Phase separation, as characterized by dynamic changes in sample turbidity, was monitored simultaneously with monomer conversion and either preceded or was coincident with network gelation. Dynamic mechanical analysis shows a broadening of the tan delta peak and secondary peak formation, characteristic of phase-separated materials, indicating one phase rich in prepolymer and another depleted form upon phase separation. In certain cases, PIPS leads to an enhanced physical reduction of volumetric shrinkage, which is attractive for many applications including dental composite materials.

A Study of Shrinkage Stress Reduction and Mechanical Properties of Nanogel-Modified Resin Systems.

A series of nanogel compositions were prepared from urethane dimethacrylate (UDMA) and isobornyl methacrylate (IBMA) in the presence of a thiol chain transfer agent. The linear oligomer of IBMA was synthesized by a similar solution polymerization technique. The nanogels were prepared with different crosslinker concentrations to achieve varied branching densities and molecular weights. The prepolymers were dispersed in triethylene glycol dimethacrylate at loading levels ranging from 10 wt% to 50 wt%. Photopolymerization reaction kinetics of all prepolymer modified systems were enhanced relative to the nanogel-free control during early stage polymerization while limiting conversion was similar for most samples. Volumetric polymerization shrinkage was reduced proportionally with the prepolymer content while the corresponding decrease in polymerization stress was potentially greater than an additive linear behavior. Flexural strength for inert linear polymer-modified systems decreased significantly with the increase in the prepolymer content; however, with an increase in the crosslinker concentration within the nanogel additives, and an increase in the concentration of residual pendant reactive sites, flexural strength was maintained or improved regardless of the nanogel loading level. This demonstrates that covalent attachment rather than just physical entanglement with the polymer matrix is important for effective polymer mechanical reinforcement by nanogel additives. Reactive nanogel additives can be considered as a practical, generic means to achieve substantial reductions in polymerization shrinkage and shrinkage stress in common polymers.

Effect of thickness on the degree of conversion of two bulk-fill and one conventional posterior resin-based composites at high irradiance and high temporal resolution.

OBJECTIVES: This study: 1) measures the effect of sample thickness and high irradiance on the depth-dependent time delay before photopolymerization reaction onset; 2) determines if exposure reciprocity exists; 3) measures the conversion rate at four irradiance levels; 4) determines the time, t0, at which the maximum DC rate is reached for two bulk-fill and one conventional posterior resin-based composites (RBCs). METHODS: Tetric PowerFill IVA shade (Ivoclar Vivadent) and Aura bulk-fill ultra universal restorative (SDI), and one conventional posterior resin-based composite (RBC), Heliomolar A3 (Ivoclar Vivadent), that were either 0.2 mm, 2 mm, or 4 mm thick were photocured using a modified Bluephase G4 (Ivoclar Vivadent) light-curing unit (LCU) that delivered a single emission band (wavelength centered at 449 nm). The same radiant exposure of 24 J/cm2 was delivered at irradiances ranging from 0.5 to 3 W/cm2 by adjusting the exposure time. PowerFill was also photocured for 3 s or 6 s using a Bluephase PowerCure LCU (Ivoclar Vivadent) on the 3 s mode setting. The degree of conversion (DC) was measured in real-time at a high temporal resolution at 30 °C using Attenuated Total Reflection (ATR) FTIR spectroscopy with a sampling rate of 13 DC data points per second. The DC data were analyzed using a phenomenological autocatalytic model. The RBC viscosity was measured at 21 °C and 30 °C. Light transmission through the RBC samples at 22 °C was monitored with time to calculate the extinction coefficients of the RBCs. RESULTS: The time delay before photopolymerization started increased as the RBC thickness increased and the irradiance decreased. An autocatalytic model described the DC data. The time t0 was less than 77 ms for the 0.2 mm thick samples of PowerFill irradiated using the highest irradiance of 3 W/cm2. Among the three RBCs for each sample thickness and irradiance level, the PowerFill had the smallest time t0. There was a time delay of 0.59 s and 1.25 s before the DC started to increase at the bottom of 4 mm thick samples for the PowerFill and Aura, respectively, when an irradiance of 1 W/cm2 was delivered. The time delay increased to 3.65 s for the Aura when an irradiance of 0.5 W/cm2 was delivered. The extinction coefficients near 449 nm were 0.78 mm-1, 0.76 mm-1, and 1.55 mm-1 during the first 2 s after the start of photocuring of PowerFill, Aura, and Heliomolar, respectively. Only PowerFill followed exposure reciprocity. At T = 30 °C, the viscosity was 3400, 17000, and 5200 Paˑs for PowerFill, Aura, and Heliomolar, respectively. SIGNIFICANCE: The time delay between when photopolymerization starts at the top and bottom of 2- or 4-mm thick RBC restorations may affect the structural integrity of the bond between the tooth and the bottom of the restoration. Only PowerFill followed exposure reciprocity between irradiance levels of 0.5 to 3 W/cm2. Exposure reciprocity did not occur for Aura or Heliomolar, neither of which are optimized for short light exposure or high irradiance conditions.

Delayed Gelation Through Chain-Transfer Reactions: Mechanism For Stress Reduction In Methacrylate Networks.

Chain-transfer reactions from thiols to methacrylates are expected to delay gelation and possibly reduce stress at the bonded interface of dental restorations. Thiol additives with varying structures were combined with a dimethacrylate commonly used in dental materials. Polymerization stress/modulus development were monitored by a tensometer/rheometer, respectively, both coupled with RT-NIR. For all thiol-modified materials, conversion and modulus were 5-25 % higher than the control, and maximum reaction rate was 25-50 % lower. Gel point conversions were 12-22 % (control=5 %), and deceleration was observed at later stages in conversion (30-60 %; control=15 %). Consequently, even with increased conversion/modulus, stress values were either equal or reduced compared to the control. This approach does not require any modification in the bonding/photoactivation procedures, and seems promising for stress management not only in polymeric dental materials, but also for other applications of glassy, crosslinked photopolymers, as long as thiol volatility is addressed.

Characterization of dimethacrylate polymeric networks: a study of the crosslinked structure formed by monomers used in dental composites.

The resin phase of dental composites is mainly composed of combinations of dimethacrylate comonomers, with final polymeric network structure defined by monomer type/reactivity and degree of conversion. This fundamental study evaluates how increasing concentrations of the flexible triethylene glycol dimethacrylate (TEGDMA) influences void formation in bisphenol A diglycidyl dimethacrylate (BisGMA) co-polymerizations and correlates this aspect of network structure with reaction kinetic parameters and macroscopic volumetric shrinkage. Photopolymerization kinetics was followed in real-time by a near-infrared (NIR) spectroscopic technique, viscosity was assessed with a viscometer, volumetric shrinkage was followed with a linometer, free volume formation was determined by positron annihilation lifetime spectroscopy (PALS) and the sol-gel composition was determined by extraction with dichloromethane followed by (1)H-NMR analysis. Results show that, as expected, volumetric shrinkage increases with TEGDMA concentration and monomer conversion. Extraction/(1)H-NMR studies show increasing participation of the more flexible TEGDMA towards the limiting stages of conversion/crosslinking development. As the conversion progresses, either based on longer irradiation times or greater TEGDMA concentrations, the network becomes more dense, which is evidenced by the decrease in free volume and weight loss after extraction in these situations. For the same composition (BisGMA/TEGDMA 60-40 mol%) light-cured for increasing periods of time (from 10 to 600 s), free volume decreased and volumetric shrinkage increased, in a linear relationship with conversion. However, the correlation between free volume and macroscopic volumetric shrinkage was shown to be rather complex for variable compositions exposed for the same time (600 s). The addition of TEGDMA decreases free-volume up to 40 mol% (due to increased conversion), but above that concentration, in spite of the increase in conversion/crosslinking, free volume pore size increases due to the high concentration of the more flexible monomer. In those cases, the increase in volumetric shrinkage was due to higher functional group concentration, in spite of the greater free volume. Therefore, through the application of the PALS model, this study elucidates the network formation in dimethacrylates commonly used in dental materials.

Photopolymerization shrinkage-stress reduction in polymer-based dental restoratives by surface modification of fillers.

OBJECTIVES: This research explores the use of polymer brushes for surface treatment of fillers used in polymer-based dental restoratives with focus on shrinkage stress reduction. The influence of interfacial reactive groups on shrinkage stress is explored. METHODS: Oligomers of varying lengths and with varying number of reactive groups along the length were synthesized by modifying commercial oligomers. Surface of silica fillers (OX50) was treated with methylaminopropyltrimethoxysilane and this was further reacted with the synthesized oligomers to obtain a series of polymer brushes on the surface. Fillers modified with γ-methacryloxypropyltrimethoxysilane were used as a control. Filler surface treatment was confirmed using diffuse reflectance spectroscopy and thermogravimetric analysis. Fillers were added at 30 wt % to a resin made of BisGMA/TEGDMA and polymerization kinetics, shrinkage stress, volumetric shrinkage, flexural strength and modulus, viscosity were measured. RESULTS: Composites with polymer brush functionalized fillers showed up to a 30 % reduction in shrinkage stress as compared to the control, with no reduction in flexural strength and modulus. Shrinkage stress reduced with increasing length of the polymer brush and increased with increase in number of reactive groups along the length of the polymer brush. SIGNIFICANCE: The interface between inorganic fillers and an organic polymer matrix has been utilized to reduce shrinkage stress in a composite with no compromise in mechanical properties. This study gives insights into the stress development mechanism at the interface.

Visible-Light Photoinitiation of (Meth)acrylate Polymerization with Autonomous Post-conversion.

Conversion plateaus rapidly in radical photopolymerizations (RPPs) following discontinuation of irradiation due to rapid termination of reactive radicals, which restricts the wider use of RPPs in applications that involve nonuniform light access including those with attenuated light transmission or irregular surfaces. Based on our recent report of a radical dark-curing photoinitiator (DCPI) that continues polymerization beyond the cessation of irradiation by enabling latent redox initiation with photo-released amine in the presence of a suitable oxidant, we developed a new DCPI with an absorption spectrum that extends well into the visible range. Our design process involved a series of computational investigations of candidate molecules, including a systematic study of substituents and their position-dependent effects on absorption characteristics, electronic transitions, and the photochemical mechanism and its associated energetics. Our quantum chemical computations identified the target compound 5,7-dimethoxy-6-bromo-3-aroylcoumarin-DMPT/BPh4 and predicted that it would facilitate the dark-curing mechanism by concurrent photo-radical generation and photo-induced release of an efficient redox reductant under visible irradiation. This reductant-tethered chromophore was then synthesized and optically characterized with UV-vis spectroscopy that revealed its strong visible-light absorption with a molar absorptivity of 5710 M-1 cm-1 at 405 nm and 50 M-1 cm-1 at 455 nm. We then demonstrated extensive dark-curing of >35% additional conversion over 25 min following brief activation of the shelf-stable one-part system by irradiation with a 455 nm LED that was ceased at 20% conversion. In contrast, shuttering irradiation of the control formulation at that same point resulted in immediate cessation of conversion, which plateaued at 20%. We determined a remarkable initiator efficiency of 2.82 that results from the additional redox-generated radicals with a 77% photo-reductant generation quantum yield. The combination of superior photo- and dark-curing efficiencies of this new visible DCPI is expected to open new application opportunities in RPP, especially those involving resins that are highly light attenuating, surfaces that possess irregular features that produce uneven irradiance, and production lines where continued dark-curing downstream of the light activation step enhances line efficiencies.

Relocation and reinforcement of the adhesive/composite interface with spontaneous amine-peroxide interfacial polymerization.

OBJECTIVES: This study demonstrates a spontaneous redox polymerization process located at the adhesive-composite interface that precedes photocure of the composite with the intent to improve bonding. METHODS: An aromatic amine and benzoyl peroxide redox initiator system was partitioned between BAPO-photoinitiated BisGMA/HEMA adhesive and BisGMA/TEGDMA resin-composites. The composite was placed on the photocured adhesive layer with a brief delay before photopolymerization of the composite layer. Micro-tensile bond strength between the adhesive and composite was assessed in comparison with the non-redox active control materials. RESULTS: The presence of amine or peroxide in these resins without the redox initiation contribution enhanced both the rate and the final conversion of the BAPO-based photopolymerizations. Control formulations using redox-only initiation showed active polymer formation starting at approximately 30 s when physical mixing of the redox components was involved; however, simply by waiting 60 s between composite placement and photocure provided adequate time for passive interfacial diffusion of benzoyl peroxide from the pre-cured adhesive into the overlaid aromatic amine-containing composite such that a sufficient degree of redox initiated interfacial polymerization occurred prior to the composite photocure. The result was a significant increase in the adhesive to composite micro-tensile bond strength with the failure site moved away from the mainly interfacial failure noted for the control. SIGNIFICANCE: The stress-free autonomous pre-conversion of a redox-initiated thin film of composite that then provides a compositionally homogeneous interface for composite photopolymerization offers a means to enhance at least short-term bond strength between the adhesive and composite phases during restorative placement.

3D printing restorative materials using a stereolithographic technique: a systematic review.

OBJECTIVE: To present through a systematic review a qualitative analysis of studies published on stereolithography-based 3D printing of restorative materials and their clinical applicability. METHODS: The literature search was conducted based on the question: "What is the state-of-the-art of available restorative materials for 3D printing based on stereolithography?" Online search was conducted in three databases (MEDLINE/PubMed, Scopus and Web of Science) with no restriction for year of publication. Data are reported based on PRISMA, including publication details such as authors and their countries, year and journal of publication, and study design. The synthesis is focused on describing the dental restorative materials and properties evaluated, applied methods, 3D printers used and clinical applicability. RESULTS: Studies that fit the inclusion criteria were performed in Asia (21), Europe (16) and USA (10), mostly using polymer-based restorative materials (38) for 3D printing constructs. Stereolithographic-printed ceramic-based restorative structures were evaluated by 9 studies. Many studies reported on dimensional accuracy (14), strength (11) and surface morphology (9) of the printed structures. Antibacterial response, cytotoxicity, internal and marginal fit, fracture and wear resistance, density, viscosity, elastic modulus, hardness, structural shrinkage and reliability, degree of conversion, layer cure depth, fatigue, and color were also evaluated by the included studies. Many of them (11) published a proof of concept as an attempt to demonstrate the clinical feasibility and applicability of the technology to print restorative materials, but only 5 studies actually applied the 3D printed restorative structures in patients, which highlights an increasing interest but limited early-stage translation. SIGNIFICANCE: The fast expansion of stereolithographic-based 3D printing has been impressive and represents a great technological progress with significant disruptive potential. Dentistry has demonstrated an incredible willingness to adapt materials, methods and workflows to this promising digital technology. However, esthetic appearance, wear resistance, wet strength and dimensional accuracy are the main current clinical limitations restricting the progression to functional part production with 3D printing, which may explain the absence of clinical trials and reports on permanent/definitive dental restorative materials and structures.

Evaluation of a photo-initiated copper(I)-catalyzed azide-alkyne cycloaddition polymer network with improved water stability and high mechanical performance as an ester-free dental restorative.

OBJECTIVE: The objective is to develop and characterize an ester-free ether-based photo-CuAAC resin with high mechanical performance, low polymerization-induced stress compared with common BisGMA/TEGDMA (70/30) resins, and improved water stability in comparison to previously developed urethane-based photo-CuAAC resins. METHODS: Triphenyl-ethane-centered ether-linked tri-azide monomers were synthesized and co-photopolymerized with ether-linked tri-alkyne monomers under visible light irradiation using a copper(II) pre-catalyst and CQ/EDAB as the initiator. The ether-based CuAAC formulation was investigated for thermo-mechanical properties, polymerization kinetics and shrinkage stress, and flexural properties with respect to a conventional BisGMA/TEGDMA (70/30) dental resin. In addition, both the ether-based CuAAC resin and the urethane-based CuAAC resin were examined for their water stability using the BisGMA/TEGDMA (70/30) resin as a control. RESULTS: The ether-based CuAAC network (AK/AZ-1) exhibited a slightly lower glass-transition temperature compared with the BisGMA/TEGDMA network (108 °C vs 128 °C), but because of its much sharper glass transition, the AK/AZ-1 CuAAC-network maintained storage modulus higher than 1 GPa up to 100 °C. In addition, the ether-based AK/AZ-1 network exhibited reduced shrinkage stress (0.56 MPa vs 1.0 MPa) and much higher flexural toughness (7.6 MJ/m3vs 1.6 MJ/m3) while showing slightly lower flexural modulus and slightly higher flexural strength compared with the BisGMA/TEGDMA network. Moreover, the ether-based AK/AZ-1 CuAAC network displayed comparable water stability in comparison to the BisGMA/TEGDMA network with slightly higher water sorption (46 µg/mm3vs 38 µg/mm3) and much lower water solubility (2.3 µg/mm3vs 4.4 µg/mm3). SIGNIFICANCE: Employing the ether-based hydrophobic CuAAC formulation significantly improved the water stability of the CuAAC network compared with previously developed urethane-based CuAAC networks. Furthermore, compared with the conventionally used BisGMA/TEGDMA formulation, the reduced shrinkage stress, comparable flexural strength/flexural modulus, and the superior flexural toughness of the ether-based CuAAC network make it a promising ester-free alternative to the currently widely-used methacrylate-based dental restoratives.

Suppression of hydrolytic degradation in labile polymer networks via integrated styrenic nanogels.

OBJECTIVE: The objective of this study was to demonstrate an approach with potential to increase the life of dental restorative polymers in water, by maintaining their strength and toughness with varied content of inert or reactive styrenic pre-polymeric additives. It was hypothesized that addition of styrene-co-divinylbenzene nanogels to a conventional dimethacrylate resin (e.g. TEGDMA) would reduce its susceptibility towards hydrolytic degradation, while maintaining equivalent mechanical properties. METHODS: Polymerization kinetics and functional group conversions were determined by Fourier transform infrared spectroscopy. Triple-detection gel permeation chromatography was used for nanogel particle characterization. A goniometer was used to measure water contact angle on experimental and control photocured polymers. Hydrolytic degradation and mass loss evaluation was performed after extended water storage of an intentionally hydrolytically degradable polymer. Resin viscosity was determined rheometrically and polymer mechanical properties were evaluated using three-point flexural testing with TEGDMA-nanogel formulations. RESULTS: The polymer network with highest level of nanogel loading (50 wt%) and the highest level of internal nanogel crosslinking (50 mol%) had the lowest degree of equilibrium swelling ratio and mass loss. The flexural modulus and ultimate strength of polymerized TEGDMA and styrenic nanogel-modified TEGDMA were not statistically different (p > 0.05). SIGNIFICANCE: Due to improved shielding throughout the bulk of methacrylate-based polymers, including an example with an intentionally hydrolytically labile network structure, and a dramatic decrease of water uptake while maintaining equivalent mechanical properties, styrenic nanogel additives especially in high loading levels provide an excellent alternative to eliminate the adverse effects of water and presumably salivary fluids.