Letter www.acsami.org
High-Performance Nano-Photoinitiators with Improved Safety for 3D Printing Yanyang Han,†,‡ Fei Wang,†,§ Chin Yan Lim,⊥ Hong Chi,|| Dairong Chen,‡ FuKe Wang,*,§ and Xiuling Jiao*,‡ ‡
School of Chemistry & Chemical Engineering, Shandong University, Jinan 250100, P. R. China Polymeric Materials Department, Institute of Materials Research and Engineering, Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, #08-03 Innovis, 138634 Singapore ⊥ Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), 8a Biomedical Grove, #06-06, 138648, Singapore || Shandong Provincial Key Laboratory of Fine Chemicals, School of Chemistry of Pharmaceutical Engineering, Qilu University of Technology, Jinan 250353, China §
S Supporting Information *
ABSTRACT: In this work, we report the first hybrid nanosized photoinitiators with low cytotoxicity and migration by coupling of polyhedral oligomeric silsesquioxanes (POSS) to benzophenone derivatives. This new series of photoinitiators were fully characterized and showed many favorable properties such as uniform sizes, extremely low tendency to migrate, less effect on resin viscosity, enhanced thermal stability and mechanical strength, increased photoactivity, and significantly lower cell toxicity compared to their corresponding benzophenone molecules. The utility of these hybrid nanosized photoinitiators in 3D printing was demonstrated in printing of various 3D structures with high resolution and accuracy.
KEYWORDS: photoinitiators, benzophenone, 3D printing safety, printable resin, additive manufacturing, POSS
T
food, raising significant food safety concerns.12 Undoubtedly, as the 3D printing market and interests shift rapidly from prototyping to end-use product manufacturing and bioprinting, the migration of photoinitiators from printed objects will soon become a critical safety issue. To improve the safety of photopolymers, researchers have developed various polymeric photoinitiators, derived from grafting or condensing low-molecular-weight photoinitiators to linear,13−15 dendritic,16 or hyperbranched17 polymers. Low extractability has been reported for these polymeric photoinitiators, but this is usually accompanied by reduced photoactivity compared to their corresponding low-molecularweight analogues. Only a few polymeric photoinitiators with enhanced photoactivity have been reported.13−16 Furthermore, the coupling of photoinitiators to large molecular weight polymers generally leads to significant increases in resin viscosity. The low reactivity and high viscosity of polymeric photoinitiators, as well as inconvenient purification procedures, have thus far limited their applications in stereolithography-
hree-dimensional (3D) printing, also known as additive manufacturing, is an emerging technology and has started to evolve into the next-generation manufacturing technology.1−5 3D printing is expected to change the whole industry and revolutionize the traditional manufacturing process. Various 3D printing techniques and methods have been developed to build 3D structures and objects. Among these, stereolithography (SLA) technology is the first 3D printing technique to be developed that has sustained utility in additive manufacturing because of its superior resolution, accuracy, and good z-axis strength compared to other printing techniques.6 SLA printing involves layer-by-layer rapid photopolymerization of a light-sensitive liquid resin to solid polymers by UV light or laser,7−9 with free radical photopolymerization (FRPP) of acrylate or methacrylate being the major technique.10,11 In FRPP, radicals generated from photoinitiators upon light excitation are used to initiate the polymerization of acrylate polymers. After photopolymerization, photoinitiators remaining in the polymer matrix can readily migrate out of the matrix with time, because of their fairly low molecular weight, leading to negative consequences. For instance, small photoinitiators of 200−250 Da used in food packaging, such as 4-methyl benzophenone (4-MBP) and isopropyl thioxanthone (ITX), were found to migrate from the packaging materials into the © 2017 American Chemical Society
Received: June 12, 2017 Accepted: September 6, 2017 Published: September 6, 2017 32418
DOI: 10.1021/acsami.7b08399 ACS Appl. Mater. Interfaces 2017, 9, 32418−32423
Letter
ACS Applied Materials & Interfaces
Figure 1. Comparison of the 1H NMR spectra of starting materials HDBP and POSS−Br and the product POSS−DBP. R substituent on POSS here represents the cyclohexyl group, and the small peak at δ = 0.83 ppm is attributed to hexane residue.
nanoparticle. As shown in Scheme S1, benzophenone type photoinitiators, 4-hydroxylacetophenone (HAP), 4-hydroxylbenzophenone (HBP), and 4- hydroxyl(dimethylamino)benzophenone (HDBP) with initiating wavelengths at 277, 290, and 345 nm, respectively, were coupled to mono(bromopropyl)-substituted POSS (POSS-Br). As HDBP is not commercially available, it was synthesized in the lab with high yield through the reaction of corresponding amide with N,N-dimethylaniline in the presence of phosphoryl chloride (Scheme S2).25 POSS-Br was prepared from trisilanocyclohexyl POSS, and its purity and structure was confirmed by the proton nuclear magnetic resonance (1H NMR) spectrum (Figure 1). The triplet at d = 3.43 ppm was assigned to −CH2Br in the bromopropyl group. The coupling of the small molecular photoinitiators with POSS-Br was achieved through the reaction of POSS−Br with benzophenone derivatives containing hydroxyl group in the presence of potassium carbonate and a catalytic amount of 18-crown-6 as the phase transfer agent.26 The new POSS-coupled photoinitiators, named as POSS-AP, POSS-BP, and POSS-DBP, were successfully obtained with high yield after the coupling reactions and purification by silica gel chromatography. The chemical structures of these new photoinitiators were confirmed by NMR (Figures S3 S4), with the spectrum for POSS-DBP shown as an example in Figure 1. A new triplet appearing at d = 4.0 ppm was attributed to the
based 3D printing technology, which requires fast solidification and low resin viscosity. Here we report a new series of nanosized photoinitiators generated by coupling benzophenone derivatives to polyhedral oligomeric silsesquioxanes (POSS). POSS was chosen in this work for its well-defined nanostructures, facile chemical modification, biocompatibility, and the commercial availability of various useful precursors for modification.18−20 For example, POSS-based proton donor21 and acrylate monomers22 have been developed and tested in photopolymerization. In our strategy, new photoinitiators can be facilely obtained by simple coupling of the hard nanosized POSS core with commercially available photoinitiators. Characterization of structures, thermal stability, photoactivity, and evaluation of effects on resin viscosity and migration property were conducted on the asobtained hybrid photoinitiators. The cytotoxicity of the new hybrid photoinitiators was demonstrated by cell proliferation assays with photopolymerized structures initiated by hybrid photoinitiators and their corresponding low-molecular-weight parent photoinitiators. Benzophenone (BP) derivatives are low-cost and highly efficient photoinitiators that have become the preferred choice for industrial uses.23,24 In this work, three easily available BP derivatives with different initiating absorption wavelengths were selected as parent photoinitiators. A hydroxyl group in the parent photoinitiators was included for coupling with the POSS 32419
DOI: 10.1021/acsami.7b08399 ACS Appl. Mater. Interfaces 2017, 9, 32418−32423
Letter
ACS Applied Materials & Interfaces −CH2 group that links POSS to the phenol ring in HDBP. In the low field region (6.7−7.8 ppm), characteristic peaks of aromatic protons on the DBP ring appeared with slight downfield shift as compared with the pristine HDBP (Figure S1). These new photoinitiators showed better solubility than their corresponding polar BP derivatives in organic solvents such as chloroform, THF, hexane, and toluene, mainly due to the coupled hydrophobic POSS moiety, which contains seven cyclohexyl groups. UV−vis spectral analysis of the new photoinitiators in methylene chloride showed that the coupling of benzophenone initiators with POSS nanoparticles had only slight effects on their respective major absorption wavelengths, suggesting little impact on their optical properties. As shown in Figure 2 and
be used within a broader range of working temperatures compared to traditional benzophenone initiators. The photoactivity of the new photoinitiators was investigated by photopolymerization conversion of methyl methacrylate (MMA) or methacrylate (MA) under air atmosphere with triethanolamine (TEA) as co-initiator in a Luzchem photoreactor. For simplicity, the results for only POSS-BP, POSSDBP, and their corresponding small benzophenone photoinitiators were listed in Table 2 as POSS-AP performed Table 2. Photoactivity Studies of the New Photoinitiatorsa entry
resin
1
9 10
0.5 mL MMA 0.5 mL MMA 0.5 mL MMA 0.5 mL MMA 0.5 mL MMA 0.5 mL MMA 0.5 mL MMA 0.5 mL MMA 0.5 mL MA 0.5 mL MA
11 12
0.5 mL MA 0.5 mL MA
2 3 4 5 6 7 8
Figure 2. Comparison of the UV−vis spectra of benzophenone photoinitiators before and after coupling with POSS.
PI content (μmol/g)b
time (h)
HDBP
10
5
22.7%
POSSDBP HDBP
10
5
20
3
27.8% (+22%) 21.1%
POSSDBP HBP
20
3
10
5
POSS-BP
10
5
HBP
20
3
POSS-BP
20
3
HDBP POSSDBP 4-HBP POSS-BP
10 10
5 5
10 10
5 5
initiator
convn (%)c
27.8% (+32%) 21.6% 70.7% (+227%) 9.7% 25% (+158%) 28.6% 35.8% (+25%) 25.7% 72.0% (+180%)
a Total light density used: 200 cd•sr/m2. bMole number of photoinitiators per gram of photopolymer resin. cValue in bracket indicate the conversion enhancement ratio of new photoinitiators comparing to their corresponding small molecular analogues.
Table 1, no major absorption changes before and after coupling to POSS were observed for HDBP, whereas HAP and HBP showed only slight red shifts of less than 10 nm after coupling to POSS. Interestingly, we found that the absorption coefficients of the new photoinitiators were all larger than that of their corresponding small molecule analogues, suggesting that these new photoinitiators may exhibit higher photoactivity. The thermal stability of the new photoinitiators were studied by thermal gravimetric analysis (TGA) under nitrogen atmosphere. Remarkably enhanced thermal stability was found for these new POSS-coupled photoinitiators compared to their corresponding small molecular analogues (Table 1 and Figure S5−S7). For instance, the decomposition temperature (Td) of HDBP was found to be at 265 °C, whereas Td of POSS-DBP was increased to 344 °C. The enhancement of thermal stability after introduction of the POSS moiety had been observed in our previous studies,26 and was attributed to the greater thermal barrier capability of POSS because of its low thermal conductivity. The enhanced thermal stability of the new POSS-coupled photoinitiators indicates these initiators can
similarly to POSS-BP. As shown in Table 2, both new POSScoupled photoinitiators showed enhanced photoactivity compared to their corresponding small molecular benzophenone analogues. POSS-BP showed a 150−230% increase in polymer conversion over HBP, whereas POSS-DBP showed 20−30% more polymer conversion than HDBP. It is interesting to note that POSS-DBP and POSS-BP have different concentration dependent effects. POSS-DBP showed a concentration dependent manner, a higher POSS-BP concentration resulted in a lower photoactivity enhancement effect. At low initiator concentration (10 μmol/g), a 22% increase of polymer conversion (entries 1, 2) was observed for POSS-DBP compared to HDBP, and further enhancement (32%) was observed when the initiator concentration was doubled (entries 3, 4). By contrast, while low POSS-BP concentration (10 μmol/g) greatly enhanced polymer conversion (227%, entries 5−6) over HBP, the positive enhance-
Table 1. Comparison of the physical Properties of New Photoinitiators and Their Corresponding Parent Molecules
mol wt thermal stability Td (°C) λmax (nm) ε (× 104 L mol−1 cm−1)
HAP
POSS-AP
HBP
POSS-BP
HDBP
POSS-DBP
136 207 272 1.02
1147 280 277 1.38
198 246 280 1.06
1209 278 290 1.41
241 265 345 2.49
1252 344 345 2.94
32420
DOI: 10.1021/acsami.7b08399 ACS Appl. Mater. Interfaces 2017, 9, 32418−32423
Letter
ACS Applied Materials & Interfaces
Figure 3. (a) HeLa cells grown in 0.75× HBP media (top row) or POSS-BP media (bottom row) for the first 1, 5, and 13 h. (b-d) Confluence plots showing growth rates of HeLa cells in different concentrations of photoinitiator media for 144 h (6 days). (e) Amount of photoinitiators extracted from cured PEGDA and HDDA polymers.
The cytotoxicity of the new POSS-coupled photoinitiators was evaluated by cell toxicity tests conducted on cured polyethylene (glycol) diacrylate (PEGDA), which was photopolymerized by using either the POSS-coupled photoinitiator, POSS-BP, or its corresponding small molecular initiator, HBP.29 The cured polymer sheets of 1 mm thickness were cut into 10 × 10 mm squares and incubated in 1 mL of HeLa cell media (Dulbecco’s modified Eagle medium supplemented with 10% fetal bovine serum) for 72 h at 37 °C. The conditioned media was harvested and centrifuged for 10 min to remove particulates and diluted to appropriate concentration with normal media before adding to cells. HeLa cells were seeded at 12 000 cells/well in 24-well plates, 1 day before addition of conditioned media to achieve a density of ∼10−
ment effect was reduced to 158% (entries 7, 8) upon doubling the concentration of POSS-BP. The greater photoactivity of the POSS-coupled initiators observed was likely due to the high steric effect of POSS, as illustrated by computer simulation (Figure S9). This was in line with the well-established concept that free radicals can be stabilized by high steric structures or hyperconjugation.26−28 Because the benzophenone and POSS moieties were not conjugated in the POSS-coupled photoinitiators, stability of the radical would primarily be conferred by the steric effect of POSS. The large-sized POSS core and cyclohexyl-substituted periphery shield the benzophenone moiety, thus extending the half-life of the generated radicals, and giving rise to enhanced photoactivity. 32421
DOI: 10.1021/acsami.7b08399 ACS Appl. Mater. Interfaces 2017, 9, 32418−32423
Letter
ACS Applied Materials & Interfaces
Figure 4. Pictures of 3D printed objects by POSS-DBP photoinitiator using a DLP printer with HDDA resin containing 3 wt % POSS-coupled photoinitiators and 0.05 wt % of photoabsorbers.
coupled photoinitiators, functioning as highly efficient photoinitiators as well as mechanical reinforcement nanofillers. The new POSS-coupled photoinitiators thus exhibit many advantageous qualities such as improved safety and biocompatibility, enhanced photoactivity and better mechanical properties, which make them highly suitable for applications in stereolithography-based 3D printing. To demonstrate their potential applications, we mixed HDDA resin with POSScoupled initiators and printed on a digital light processing (DLP) printer (Brand: LittleRP) with a DLP projector as light source (Acer P1283).30 The viscosity of the HDDA resin (η = 8.726 ± 0.35 mm2/s) was measured before and after mixing with the POSS-coupled photoinitiators, and a slight increase of
