Thiol-acrylate Photopolymerization Research Articles

Thermo-Responsive Shape Memory Vanillin-Based Photopolymers for Microtransfer Molding.

Novel thermo-responsive shape-memory vanillin-based photopolymers have been developed for microtransfer molding. Different mixtures of vanillin dimethacrylate with tridecyl methacrylate and 1,3-benzenedithiol have been tested as photocurable resins. The combination of the different reaction mechanisms, thiol-acrylate photopolymerization, and acrylate homopolymerization, that were tuned by changing the ratio of monomers, resulted in a wide range of the thermal and mechanical properties of the photopolymers obtained. All polymers demonstrated great shape-memory properties and were able to return to their primary shape after the temperature programming and maintain their temporary shape. The selected compositions weretested by the microtransfer molding technique and showed promising results. The developed thermo-responsive shape-memory bio-based photopolymers have great potential for forming microtransfered structures and devices applicable on non-flat surfaces.

Photopolymerizable chitosan hydrogels with improved strength and 3D printability

Chitosan hydrogel have presented great potential in biomedical applications due to its biocompatibility, biodegradability and characteristic similarity to native extracellular matrix. However, 3D printing of chitosan hydrogel often suffers from weak formability and poor mechanical property, limiting its further utilization. In this study, a novel chiotsan hydrogel is prepared from maleic chitosan (MCS) with high acrylate group substitution (i.e. 1.67) and thiol-terminated poly (ethylene glycol) (TPEG) via step-chain growth photopolymerization approach, which can overcome significantly the oxygen inhibition effect. Rheological property, microstructure, mechanical properties and in vitro degradation can be regulated by changing the thiol/acrylate molar ratio. There is strong intermolecular action between MCS and TPEG. Notably, photopolymerized MCS/TPEG hydrogel exhibited ~2-fold and ~ 10-fold increase in gelling rate and compressive strength, respectively, compared to pure chitosan hydrogel. Based on these results, 3D printing of chitosan hydrogel fabricated by simultaneous extrusion deposition and thiol-acrylate photopolymerization, demonstrates printing accuracy and improved scaffold stability. This 3D printing of chitosan hydrogel shows no cytotoxicity and can support adherence of L929 cells, suggesting its potential in biomedical applications such as tissue engineering and drug delivery.

Alginate/poloxamer hydrogel obtained by thiol-acrylate photopolymerization for the alleviation of the inflammatory response of human keratinocytes

Hydrogel-based wound dressings have been intensively studied as promising materials for wound healing and care. The mixed-mode thiol-acrylate photopolymerization is used in this paper for alginate/poloxamer hydrogels formation. First, the alginate was modified with thiol groups using the esterification reaction with cysteamine, and second, the terminal hydroxyl groups of poloxamer were esterified with acryloyl chloride to introduce polymerizable acrylate groups. Finally, the cross-linking reaction between the two macromers was performed to produce degradable alginate/poloxamer hydrogels. The optimum conditions for the photo-initiated reaction were studied in order to obtain high gel fractions. The resulting hydrogels have high swelling capacity in simulated physiological conditions, good elasticity and strength, and appropriate porosity, some of the physico-chemical properties required for their applications as wound dressings/patches. The biological assays show that the alginate/poloxamer hydrogels induce proliferation of human keratinocyte and have an anti-inflammatory effect on lipopolysaccharides (LPS)-activated keratinocytes by inhibiting the extracellular signal-regulated kinases (ERK)/ nuclear factor (NF)-kB/ tumor necrosis factor (TNF)-α signalling pathway. Taken together, the results showed that the chemical cross-linked alginate/poloxamer hydrogels may function as a dressing/patch applied directly on the skin lesion to heal the wound by reducing the exacerbated inflammation, the main cause of wound healing delay and local infection.

Fast gelling and non-swellable photopolymerized poly (vinyl alcohol) hydrogels with high strength

Despite their great potential in biomedical applications, the use of hydrogels has been severely limited by their swelling property and weak strength under physiological conditions. Herein, we developed nonswelling and high-strength hydrogels by a facile one-step thiol-acrylate photopolymerization of methacrylated poly (vinyl alcohol) and thiol-terminated poly (vinyl alcohol) for the first time. The hydrogels can gel rapidly within 7 s in this approach. By controlling crosslinking density and hydrophilic/hydrophobic balance of cross-linking hydrogel networks, the properties of hydrogels can be tunable and can even exhibit an excellent nonswelling behaviour under physiological conditions. Notably, the outstanding mechanical property with a compressive strength of 7.0 MPa at ~95% strain as well as no damage through compressive stress–strain tests in the allowable scope of tensile tester can also be achieved. Moreover, the hydrogel is non-toxic to L929 cells, which is favorable for promising biomedical applications as implants and tissue engineering scaffolds.

A facile and versatile route for preparation AgNp nanocomposite thin films via thiol-acrylate photopolymerization: Determination of antibacterial activity

Size, shape and distribution-controlled silver nanoparticles (AgNps) were produced by a rapid and efficient method either in solvent or in polymer matrix by which the silver ion is reduced and a polymer matrix is simultaneously generated in the presence of various photoinitiators by the means of UV light.2-Mercaptothioxanthone (TX-SH), Thioxanthone (TX) and TX + Thiophenol were used as photoinitiator systems for the polymerization of PEGMEA/PEGDA monomer mixture in the presence of AgNO3 salt. As a summary of results, it is important to note that the size and distribution of Nps depend on the photoreducing species. Therefore TX-SH, due to thiol functionality in its structure, helped production of he 7–40 nm size and distribution-controlled AgNps in polymer matrix. In-situ prepared AgNps/Polymer nanocoatings exhibited a reflected silver mirror view as a result of aggregation depending on the irradiation time. Antibacterial efficiency and susceptibility of AgNps containing nanocomposite films were examined for t E. coli, P. aeruginosa, S. aureus and B. cereus. Obtained antimicrobial results show that photochemically prepared nanocomposites considerably increase the antimicrobial activity on Gram negative bacteria compared to Gram positive bacteria.

Rational Design of Superhydrophilic/Superoleophobic Surfaces for Oil-Water Separation via Thiol-Acrylate Photopolymerization.

We report a simple, rapid, and scalable strategy to fabricate surfaces exhibiting in-air superoleophobic/superhydrophilic wetting via sequential spray deposition and photopolymerization of nanoparticle-laden thiol–acrylate resins comprising both hydrophilic and oleophobic chemical constituents. The combination of spray deposition with nanoparticles provides hierarchical surface morphologies with both micro- and nanoscale roughness. Mapping the wetting behavior as a function of resin composition using high- and low-surface-tension liquid probes enabled facile identification of coatings that exhibit a range of wetting behavior, including superhydrophilic/superoleophilic, superhydrophobic/superoleophobic, and in-air superhydrophilic/superoleophobic wetting. In-air superhydrophilic/superoleophobic wetting was realized by a dynamic rearrangement of the interface to expose a greater fraction of hydrophilic moieties in response to contact with water. We show that these in-air superoleophobic/superhydrophilic coatings deposited onto porous supports enable separation of model oil–water emulsions with separation efficiencies up to 99.9% with 699 L·m–2 h–1 permeate flux when the superhydrophilic/superoleophobic coatings are paired with 0.45 μm nylon membrane supports.

The relationship between thiol-acrylate photopolymerization kinetics and hydrogel mechanics: An improved model incorporating photobleaching and thiol-Michael addition

Biocompatible hydrogels with defined mechanical properties are critical to tissue engineering and regenerative medicine. Thiol-acrylate photopolymerized hydrogels have attracted special interest for their degradability and cytocompatibility, and for their tunable mechanical properties through controlling factors that affect reaction kinetics (e.g., photopolymerization, stoichiometry, temperature, and solvent choice). In this study, we hypothesized that the mechanical property of these hydrogels can be tuned by photoinitiators via photobleaching and by thiol-Michael addition reactions. To test this hypothesis, a multiscale mathematical model incorporating both photobleaching and thiol-Michael addition reactions was developed and validated. After validating the model, the effects of thiol concentration, light intensity, and pH values on hydrogel mechanics were investigated. Results revealed that hydrogel stiffness (i) was maximized at a light intensity-specific optimal concentration of thiol groups; (ii) increased with decreasing pH when synthesis occurred at low light intensity; and (iii) increased with decreasing light intensity when synthesis occurred at fixed precursor composition. The multiscale model revealed that the latter was due to higher initiation efficiency at lower light intensity. More broadly, the model provides a framework for predicting mechanical properties of hydrogels based upon the controllable kinetics of thiol-acrylate photopolymerization.

Photopolymerizable thiol-acrylate maleiated hyaluronic acid/thiol-terminated poly(ethylene glycol) hydrogels as potential in-situ formable scaffolds

Despite their potential in various biomedical applications, photocrosslinkable hyaluronate hydrogels have often been limited by weak formation and unsatisfied mechanical strength which can be attributed to insufficient substitution of photoactive groups on the hyaluronate backbone and the oxygen inhibition effect. In this study, a new approach for the production of hyaluronic acid (MHA) with high acrylate group substitution (i.e. 2.27) is developed. It is based on the reaction of sodium hyaluronate and maleic anhydride in dimethyl sulfoxide, which has never been reported previously. Furthermore, the thiol-acrylate photopolymerization approach is employed to prepare maleiated hyaluronic acid/thiol-terminated poly(ethylene glycol) (MHA/TPEG) hydrogels which can overcome the oxygen inhibition effect. And the hydrogels possess porous structures, high swelling ratio, and tunable degradation rate. Specifically, the hydrogels could gel quickly within 15 s and demonstrate improved stiff (G′ = 4100 Pa). The in vitro cytotoxic evaluation demonstrates that the hydrogels are cytocompatible to L929 cells. As a result, the in-situ formable hydrogel scaffolds exhibit great potential for medical applications.

Soybean Oil-Based Thermoset Films and Fibers with High Biobased Carbon Content via Thiol–Ene Photopolymerization

While a number of vegetable oil derivatives have been integrated with petroleum-based materials to prepare thermosetting polymers, existing examples usually incorporate low total biorenewable content into the final product. With the goal of generating thermosets with high biorenewable content, two different soybean oil derivatives with multifunctional thiol and acrylate groups were photocured via thiol–acrylate photopolymerization. For this purpose, l-cysteine, a nonhazardous amino acid, was coupled with epoxidized soybean oil to synthesize a mercaptanized soybean oil derivative containing multiple thiol groups. After being mixed with acrylate counterparts suitable for performing thiol–ene photopolymerizations, these monomer mixtures were processed into thermoset films (via monomer mixture film casting followed by photopolymerization) and fibers (via simultaneous electrospinning of the monomer mixture and photopolymerization in flight). The resulting materials possessed high biobased carbon content (BCC; ...

Flexible Organic–Inorganic Hybrid Solid Electrolytes Formed via Thiol–Acrylate Photopolymerization

Novel flexible organic–inorganic hybrid solid electrolytes with controlled network structures (cnHSEs) were formed via thiol–acrylate photopolymerization under UV irradiation, using a series of thiol-modified silica nanoparticles and poly(ethylene glycol) diacrylate. Because of the outstanding lithium ion mobility that is readily identifiable in the solid-state nuclear magnetic resonance spectra, the flexible cnHSEs demonstrate a relatively high ionic conductivity even at low temperature of −20 °C and up to the maximum of 7.3 × 10–4 S cm–1 at 30 °C. The ionic conductivity herein is higher than that for typical solid polymer electrolytes at the identical temperature. Additionally, the lithium ion transference number is also improved simultaneously up to 0.7 more due to the scavenger effect of silica nanoparticles embedded in the system. Moreover, the cnHSEs show a broad electrochemical stability window, and the fabricated cell comprising Li|cnHSEs|LiFePO4 exhibits a highly reversible electrochemical reacti...

Structural and thermal characteristics of photocrosslinked silk fibroin - PEG hydrogel

Hydrogels are crosslinked hydrophilic matrices for a variety of biomedical applications. Silk fibroin (SF), one of typical natural biomaterials, has been explored as base material for hydrogel. Photocrosslinked SF hydrogel containing poly(ethylene glycol) (PEG) was formulated through visible light initiated thiol-acrylate photopolymerization. The morphological, structural and thermal properties of SF - PEG hydrogel was investigated through scanning electron microscopy, X-ray diffractometry, thermogravimetry, and differential scanning calorimetry. The morphology of SF hydrogel showed dot and uneven surface with network cross-section. X-ray diffraction curves showed that the specific diffraction peaks of PEG were not changed by the intensity of the peaks were affected by sonication. Thermo-degradation behavior of SF - PEG hydrogel sonicated was significantly affected and became complex pattern compared to unsonicated ones. However, the melting endothermic temperature of SF - PEG hydrogel was not changed but the crystalline enthalpy was decreased by gelation and sonication.

Designing Visible Light-Cured Thiol-Acrylate Hydrogels for Studying the HIPPO Pathway Activation in Hepatocellular Carcinoma Cells.

Various polymerization mechanisms have been developed to prepare peptide-immobilized poly(ethylene glycol) (PEG) hydrogels, a class of biomaterials suitable for studying cell biology in vitro. Here, a visible light mediated thiol-acrylate photopolymerization scheme is reported to synthesize dually degradable PEG-peptide hydrogels with controllable crosslinking and degradability. The influence of immobilized monothiol pendant peptide is systematically evaluated on the crosslinking of these hydrogels. Further, methods are proposed to modulate hydrogel crosslinking, including adjusting concentration of comonomer or altering the design of multifunctional peptide crosslinker. Due to the formation of thioether ester bonds, these hydrogels are hydrolytically degradable. If the dithiol peptide linkers used are susceptible to protease cleavage, these thiol-acrylate hydrogels can be designed to undergo partial proteolysis. The differences between linear and multiarm PEG-acrylate (i.e., PEGDA vs PEG4A) are also evaluated. Finally, the use of the mixed-mode thiol-acrylate PEG4A-peptide hydrogels is explored for in situ encapsulation of hepatocellular carcinoma cells (Huh7). The effects of matrix stiffness and integrin binding motif (e.g., RGDS) on Huh7 cell growth and HIPPO pathway activation are studied using PEG4A-peptide hydrogels. This visible light poly-merized thiol-acrylate hydrogel system represents an alternative to existing light-cured hydrogel platforms and shall be useful in many biomedical applications.

Preparation of hybrid thiol-acrylate emulsion-templated porous polymers by interfacial copolymerization of high internal phase emulsions.

Emulsion-templated highly porous polymers (polyHIPEs), containing distinct regions differing in composition, morphology, and/or properties, are prepared by the simultaneous polymerization of two high internal phase emulsions (HIPEs) contained within the same mould. The HIPEs are placed together in the mould and subjected to thiol-acrylate photopolymerization. The resulting polyHIPE material is found to contain two distinct semicircular regions, reflecting the composition of each HIPE. The original interface between the two emulsions becomes a copolymerized band between 100 and 300 μm wide, which is found to be mechanically robust. The separate polyHIPE layers are distinguished from one another by their differing average void diameter, chemical composition, and extent of contraction upon drying.

Visible-light-initiated thiol-acrylate photopolymerization of heparin-based hydrogels.

An in situ heparin-based forming hydrogel that cures under visible-light is formulated using eosin Y as a photoinitiator with triethanolamine as an electron donor to initiate reaction of thiolated-heparin with acrylate-ended poly(ethylene glycol). Formulations and irradiation conditions are presented for control of heparin content (1.6 to 3.3% w/v), modulus (100-10,000 Pa), and gelation time (30-600 s). Encapsulation of 3T3 fibroblasts in the hydrogel gave over 96% viability for all conditions examined. In vitro characterization of epidermal growth factor released from the hydrogel confirmed that the growth factor remains bioactive. The ability to deliver growth factors, fast gelation kinetics under visible light, and independent control of physical and biochemical properties makes this system a promising candidate for use in regenerative medicine. In particular, irradiation conditions that achieve gelation in 150s are compatible with the stringent light exposure limits of the retina, which affords a wide safety margin for use with other tissues.

Degradable thiol-acrylate hydrogels as tunable matrices for three-dimensional hepatic culture

A degradable poly(ethylene glycol)-diacrylate (PEGDA) hydrogel system was developed using simple macromer formulations and visible light initiated thiol-acrylate photopolymerization. In addition to PEGDA, other components in this gelation system include eosin-Y as a photo-sensitizer, bi-functional thiol (dithiothreitol, DTT) as a dual-purpose co-initiator and cross-linker, and N-vinylpyrrolidone (NVP) as a co-monomer. Gelation was achieved through a mixed-mode step-chain growth polymerization mechanism under bright visible light exposure. Increasing photo-sensitizer or NVP concentrations accelerated photo-crosslinking and increased final gel stiffness. Increasing bi-functional thiol content in the prepolymer solution only increased gel stiffness to some degree. As the concentration of thiol surpassed certain range, thiol-mediated chain-transfer events caused thiol-acrylate gels to form with lower degree of cross-linking. Pendant peptide, such as integrin ligand RGDS, was more effectively immobilized in the network via a thiol-acrylate reaction (using thiol-bearing peptide Ac-CRGDS. Underline indicates cross-linkable motif) than through homo-polymerization of acrylated peptide (e.g., acryl-RGDS). The incorporation of pendant peptide comes with the expense of a lower degree of gel cross-linking, which was rectified by increasing co-monomer NVP content. Without the use of any readily degradable macromer, these visible light initiated mixed-mode cross-linked hydrogels degraded hydrolytically due to the formation of thiol-ether-ester bonds following thiol-acrylate reactions. An exponential growth relationship was identified between the hydrolytic degradation rate and bifunctional thiol content in the prepolymer solution. Finally, we evaluated the cytocompatibility of these mixed-mode cross-linked degradable hydrogels using in situ encapsulation of hepatocellular carcinoma Huh7 cells. Encapsulated Huh7 cells remained alive and proliferated as time to form cell clusters. The addition of NVP at a higher concentration (0.3%) did not affect Huh7 cell viability but resulted in reduction of cell metabolic activity, which was accompanied by an elevated urea secretion from the encapsulated cells.

Effects of polymerizable organoclays on oxygen inhibition of acrylate and thiol-acrylate photopolymerization

Oxygen inhibition is of great concern in radical photopolymerization. This research investigates the effects of polymerizable organoclays on oxygen inhibition of acrylate and thiol-acrylate systems. Without use of thiol monomers, oxygen inhibition is difficult to overcome, although adding acrylated polymerizable organoclays slightly enhances polymerization in air. By incorporating thiols, on the other hand, polymerization rates and conversion continue to increase until thiol concentration reaches 30 mol% reaching rates and conversions approximately 80% of those observed in nitrogen. Further improvements have been observed by adding suitable polymerizable organoclays. Addition of only 5 wt% thiolated organoclays into the thiol-acrylate systems including 20 mol% thiol enhances the conversion in air to almost identical levels of that achieved under nitrogen. Interestingly, addition of either non-reactive or acrylated organoclays usually decreases the polymerization. In addition, higher thiol conversions are achieved by adding thiolated organoclays due to increased thiol-ene reaction induced by the functional groups on the clay surfaces.

Cell–cell communication mimicry with poly(ethylene glycol) hydrogels for enhancing β-cell function

A biomimetic hydrogel platform was designed to signal encapsulated cells using immobilized cell-cell communication cues, with a focus on enhancing the survival and function of encapsulated pancreatic β-cells to treat type 1 diabetes. When MIN6 cells, a pancreatic β-cell line, were encapsulated in poly(ethylene glycol) (PEG) hydrogels, their survival and glucose responsiveness to insulin were highly dependent on the cell-packing density. A minimum packing density of 10(7) cells/mL was necessary to maintain the survival of encapsulated β-cells without the addition of material functionalities (e.g., cell adhesion ligands). While single cell suspensions can improve diffusion-limited mass transfer, direct cell-cell interactions are limited. Thus, thiolated EphA5-Fc receptor and ephrinA5-Fc ligand were conjugated into PEG hydrogels via a thiol-acrylate photopolymerization to render an otherwise inert PEG hydrogel bioactive. The biomimetic hydrogels presented here can provide crucial cell-cell communication signals for dispersed β-cells and improve their survival and proliferation. Together with the cell-adhesive peptide RGDS, the immobilized fusion proteins (EphA5-Fc and ephrinA5-Fc) synergistically increased the survival of both MIN6 β-cells and dissociated islet cells, both at a very low cell-packing density (< 2 × 10(6) cells/mL). This unique gel platform demonstrates new strategies for tailoring biomimetic environments to enhance the encapsulation of cells that require cell-cell contact to survive and function.

Photopolymerization behavior in nanocomposites formed with thiol–acrylate and polymerizable organoclays

AbstractBecause of the inherent characteristics of the thiol–ene step growth mechanism in preparation of thiol–ene photopolymer clay nanocomposites, the ratio between thiol and ene functional groups at and near the organoclay surfaces may have a significant effect on the polymerization behavior. This study investigates the influence of monomer composition and the type of polymerizable organoclay on thiol–acrylate photopolymerization behavior in preparation of photocurable clay nanocomposite systems. To this end, two types of polymerizable organoclays with acrylate or thiol functional group on the clay surfaces were compared in monomer compositions with different polarity and functionality. Real‐time infrared spectroscopy was used to characterize polymerization behavior in conjunction with photo‐DSC. The degree of clay exfoliation was evaluated using small angle X‐ray scattering and correlated with photopolymerization behavior. Higher chemical compatibility of components induced enhanced clay exfoliation resulting in increase in photopolymerization rate. By affecting the stoichiometric ratio of functional groups in the clay gallery, thiolated organoclays enhance thiol–ene reaction, whereas acrylated organoclays encourage acrylate homopolymerization. In addition, inducing more propagating thiyl radicals on the organoclay surfaces by increasing functionality of thiol monomer also facilitates thiol–ene copolymerization, whereas the increase of acrylate functionality reduces final thiol conversion. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011

Regulating MCP-1 diffusion in affinity hydrogels for enhancing immuno-isolation

Delivering cells using semi-permeable hydrogels is becoming an increasingly important direction in cell based therapies and regenerative medicine applications. Synthetic hydrogels have been functionalized with bioactive motifs to render otherwise inert polymer networks responsive. However, little effort has been focused on creating immuno-isolating materials capable of retarding the transport of small antigenic molecules secreted from the cells delivered with the synthetic carriers. Toward the goal of developing a complete immuno-isolation polymeric barrier, affinity peptide-functionalized PEG hydrogels were developed with the ability to sequester monocyte chemotactic protein 1 (MCP-1), a chemokine known to induce the chemotaxis of monocytes, dendritic cells, and memory T-cells. Affinity peptides capable of sequestering MCP-1 were identified from CCR2 (a G protein-coupled receptor for MCP-1) and incorporated within PEG hydrogels via a thiol-acrylate photopolymerization. The release of encapsulated recombinant MCP-1 from PEG hydrogels is readily tuned by: (1) incorporating affinity peptides within the network; and/or (2) altering the spacer distance between the affinity peptide and the crosslinking site. Furthermore, when pancreatic β-cells were encapsulated within these novel peptide-functionalized hydrogels, the release of cell-secreted MCP-1 was significantly reduced, demonstrating the potential of this new gel formulation to reduce the host innate immune response to transplanted cells by decreasing the recruitment and activation of host monocytes and other immune cells.

Selective detection of estradiol using a molecularly imprinted self-assembled monolayer on gold surface

Molecularly imprinted polymer (MIP) was synthesized to selectively detect estrogen-like chemicals depending on their shapes and binding characteristics to Estrogen Receptor (ER) active site. MIP was synthesized on self-assembled monolayer (SAM) formed by thiol-acrylate photopolymerization on Surface Plasmon Resonance (SPR) chip. The imprinting factor was calculated based on the shift of SPR angle at which the excitation of surface plasmons by light was minimum level. The imprinting factor, 4.3, was calculated by angle shift by SPR, which showed higher imprinting factor than the previous studies. We also validated the specificity of molecularly imprinted polymer loaded gold chip and compared the binding ability to estrogenicity known by in-vivo and in-vitro biological test. Molecular imprinting reflected the whole surface characteristics including three dimensional shape, types and location of functional groups, and distribution of interaction forces such as hydrogen bonding and van der Waals interaction. Therefore, MIP binding response could provide more insight on structure and estrogenic activity. Another purpose was to provide the basic data for future development of EDC screening array chip to find out various hormone activities at once.