We report a wavelength-selective polymerization process controlled by visible/UV light, whereby a base is generated for anion-mediated thiol–Michael polymerization reaction upon exposure at one ...wavelength (400–500 nm), while radicals are subsequently generated for a second stage radical polymerization at a second, independent wavelength (365 nm). Dual wavelength, light controlled sequential polymerization not only provides a relatively soft intermediate polymer that facilitates optimum processing and modification under visible light exposure but also enables a highly cross-linked, rigid final material after the UV-induced second stage radical polymerization. A photobase generator, NPPOC-TMG, and a photo-radical initiator, Irgacure 2959, were selected as the appropriate initiator pair for sequential thiol–Michael polymerization and acrylate homopolymerization. FT-IR and rheological tests were utilized to monitor the dual cure photopolymerization process, and mechanical performance of the polymer was characterized at each distinct stage by dynamic mechanical analysis (DMA). By demonstrating complete light control in another sequential polymerization system (thiol–Michael and thiol–ene hybrid polymerization), this initiator pair exhibits great potential to regulate many other coupled anion and radical hybrid polymerizations in both a sequential and controllable manner.
Injectable hydrogel matrices take the shape of a wound cavity and serve as scaffold for tissue repair and regeneration. Yet these materials are generally hydrophilic, limiting the incorporation of ...poorly water soluble, hydrophobic drugs. Here we show this shortcoming is circumvented through a star-shaped amphiphilic block copolymer comprising poly(ethylene glycol) and poly (propylene sulfide). This star-shaped amphiphilic polymer self-assembles in an aqueous medium into a physically stable hydrogel and effectively dissolves hydrophobic molecules delivering them at therapeutic doses. The self assembled hydrogel is a robust three-dimensional scaffold in vivo effectively promoting cellular infiltration, reducing inflammation, and wound clsoure. When combined with a hydrophobic BRAF inhibitor that promotes paradoxical mitogen-activated protein kinase (MAPK) activation in keratinocytes and wound closure, our self assembled scaffold supported dermal wound closure at a reduced drug dosage compared to administering the drug in dimethyl sulfoxide (DMSO) without a polymeric matrix. This family of star-shaped amphiphilic polymers delivers poorly water soluble active agents at a fraction of generally required dosage for efficacy and supports three-dimensional cell growth at tissue wounds, showing great promise for novel uses of hydrophobic drugs in tissue repair applications.
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Designing scaffolds for polyplex-mediated therapeutic gene delivery has a number of applications in regenerative medicine, such as for tissue repair after wounding or disease. ...Microporous annealed particle (MAP) hydrogels are an emerging class of porous biomaterials, formed by annealing microgel particles to one another in situ to form a porous bulk scaffold. MAP gels have previously been shown to support and enhance proliferative and regenerative behaviors both in vitro and in vivo. Therefore, coupling gene delivery with MAP hydrogels presents a promising approach for therapy development. To optimize MAP hydrogels for gene delivery, we studied the effects of particle size and stiffness as well as adhesion potential on cell surface area and proliferation and then correlated this information with the ability of cells to become transfected while seeded in these scaffolds. We find that the void space size as well as the presentation of integrin ligands influence transfection efficiency. This work demonstrates the importance of considering MAP material properties for guiding cell spreading, proliferation, and gene transfer.
Microporous annealed particle (MAP) hydrogels are an emerging class of porous biomaterials, formed by annealing spherical microgels together in situ, creating a porous scaffold from voids between the packed beads. Here we investigated the effects of MAP physical and adhesion properties on cell spreading, proliferation, and gene transfer in fibroblasts. Particle size and void space influenced spreading and proliferation, with larger particles improving transfection. MAP stiffness was also important, with stiffer scaffolds increasing proliferation, spreading, and transfection, contrasting studies in nonporous hydrogels that showed an inverse response. Last, RGD ligand concentration and presentation modulated spreading similar to non-MAP hydrogels. These findings reveal relationships between MAP properties and cell processes, suggesting how MAP can be tuned to improve future design approaches.
•PVA has been regarded as a superior material for preparing hydrogels because of unique structure with hydroxyl groups, excellent biocompatibility.•However, PVA hydrogel prepared by traditional ...method has some inherent shortcomings, such as severe evaporation of water and poor healing effect.•To address this issue, borax (chemical cross-link agent) and polydopmine nanoparticles have been introduced into traditional PVA hydrogels.•The new hydrogel composites exhibit stronger mechanical properties and super fast speed (10 min) of healing at room temperature.•The versatility of preparing approach are expected to find widespread interest in biomaterials, electrical skin, drug delivery and soft robots.
Self-healing is a very hot topic in hydrogel community since its close relationship with broad applications such as injectable hydrogels for cell delivery, bioinks for 3D printing, and drug delivery carriers. Considerable efforts have been devoted to fabricate hydrogels with superior self-healing ability and moderate mechanical property. But more of the reported self-healing hydrogels do not own fast self-healing behavior and high mechanical strength at the same time. Herein we report a tough hybrid hydrogel which can realize ultra-fast self-healing process. This hydrogel was prepared based on polyvinyl alcohol (PVA), borax and poly-dopamine particles (PDAPs). With the incorporation of PDAPs particles, the hybrid hydrogels exhibited higher mechanical strength and faster self-healing property than PVA-borax hydrid hydrogel only. Benefited from the rapid self-healing performance, enhanced mechanical properties, good biocompatibility and simple preparation method, this novel hybrid hydrogel is expected to have great potentials in widespread applications such as electrical skin, tissue engineering, drug delivery, 3D printing and soft robots.
The utilization of 2-(2-nitrophenyl)propyloxycarbonyl (NPPOC) as a photolabile primary amine cage enables the thiol-Michael 'click' reaction to be photo-triggered. The photolabile amine exhibits ...efficient catalytic activity upon UV irradiation and is shown to initiate the photopolymerization of tetrathiol and diacrylate comonomers via Michael addition.
Here, a process is introduced for forming dual stage thiol-Michael/acrylate hybrid networks photocured by two different wavelengths, demonstrating its use in nanoimprint lithography (NIL) and shape ...memory materials. Initiated with a visible light sensitive photobase and a UV-sensitive radical initiator, thiol-Michael-acrylate hybrid polymerizations were programmed to proceed sequentially and orthogonally, with base-catalyzed thiol-Michael photopolymerization as the first stage and radical mediated acrylate photopolymerization as the second stage. By regulating the photopolymerization formulations, i.e. thiol-to-acrylate ratios, initiator loadings and irradiation conditions, a series of materials with highly tunable mechanical performance was achieved, with ultimate Tg values ranging from 23 to 70 °C. With a photopatternable first stage and a readily reconfigurable second stage, its implementation in nanoimprint lithography (NIL) enabled surface features on the scale of 10 nm to be formed on a photopatterned substrate. Additionally, the dual stage polymer results in a relatively homogenous polymer network with a narrow glass transition temperature (Tg), which enables rapid response in applications as shape memory materials, with shape-fixity values above 95% and shape-recovery values above 99%. With its unique photocuring process and programmable mechanical properties, the two color light controlled photopolymerization can be exploited as a useful tool in a wide range of materials science applications.
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•A photo-induced multistage polymerization was achieved in the thiol-Michael/acrylate hybrid polymer system.•Nanoscale features (<10 nm) were created on the photopatterned surfaces by this multistage polymerization.•The multistage polymers were used to produce shape memory materials with simple, three-dimensional structures.
Macroporous scaffolds are being increasingly used in regenerative medicine and tissue repair. While the recently developed microporous annealed particle (MAP) scaffolds have overcome issues with ...injectability and in situ hydrogel formation, limitations with respect to tunability to be able to manipulate hydrogel strength and rigidity for broad applications still exist. To address these key issues, here hydrogel microparticles (HMPs) of hyaluronic acid (HA) are synthesized using the thiol‐norbornene click reaction and then HMPs are subsequently annealed into a porous scaffold using the tetrazine‐norbornene click reaction. This assembly method allows for straightforward tuning of bulk scaffold rigidity by varying the tetrazine to norbornene ratio, with increasing tetrazine resulting in increasing scaffold storage modulus, Young's modulus, and maximum stress. These changes are independent of void fraction. Further incorporation of human dermal fibroblasts throughout the porous scaffold reveals the biocompatibility of this annealing strategy as well as differences in proliferation and cell‐occupied volume. Finally, injection of porous HA‐Tet MAP scaffolds into an ischemic stroke model shows this chemistry is biocompatible in vivo with reduced levels of inflammation and astrogliosis as previously demonstrated for other crosslinking chemistries.
Microporous annealed particle (MAP) scaffolds generated by two consecutive bioorthogonal click reactions allow for the seeding and culture of cells in vitro and injection of the material into the stroke core in vivo. Click‐by‐click MAP gels are mechanically robust and can achieve a wide range of mechanical properties through increasing interparticle linking.
In this contribution, three o-nitrobenzyl-based photobase systems were synthesized and evaluated for visible light initiated thiol-Michael addition polymerizations. With a modified structure, the ...(3,4-methylenedioxy-6-nitrophenyl)-propyloxycarbonyl (MNPPOC) protected base performance exceeds that of the nonsubstituted 2-(2-nitrophenyl)-propyloxycarbonyl (NPPOC) protected base and an ITX sensitized photobase system, with respect to both long-wavelength light sensitivity and photolytic efficiency. In material synthesis, MNPPOC-TMG is capable of initiating photo thiol-Michael polymerization efficiently and orthogonally with only limited visible light exposure and generating a highly homogeneous cross-linked polymer network. This approach enables the thiol-Michael “click” reaction to be conducted with a low-energy, visible light irradiation and, thus, expands its applications in biocompatible and UV sensitive materials.
Synthetic polymer approaches generally lack the ability to control the primary sequence, with sequence control referred to as the holy grail. Two click chemistry reactions were now combined to form ...nucleobase‐containing sequence‐controlled polymers in simple polymerization reactions. Two distinct approaches are used to form these click nucleic acid (CNA) polymers. These approaches employ thiol–ene and thiol‐Michael reactions to form homopolymers of a single nucleobase (e.g., poly(A)n) or homopolymers of specific repeating nucleobase sequences (e.g., poly(ATC)n). Furthermore, the incorporation of monofunctional thiol‐terminated polymers into the polymerization system enables the preparation of multiblock copolymers in a single reaction vessel; the length of the diblock copolymer can be tuned by the stoichiometric ratio and/or the monomer functionality. These polymers are also used for organogel formation where complementary CNA‐based polymers form reversible crosslinks.
Klick für Klick: Eine Methode zur sequenzkontrollierten Synthese von Polymeren basiert auf orthogonalen Thiol‐X‐Klick‐Reaktionen. In Kombination mit funktionellen Seitengruppen im Allgemeinen und Nucleobasen im Besonderen ermöglicht dieser Ansatz die robuste, einfache und skalierbare Herstellung von neuartigen, hoch funktionalisierten Materialien (Trt=Trityl).
An efficient visible-light-sensitive photobase generator for thiol-Michael addition reactions was synthesized and evaluated. This highly reactive catalyst was designed by protecting a strong base ...(tetramethyl guanidine, TMG) with a visible-light-responsive group which was a coumarin derivative. The coumarin-coupled TMG was shown to exhibit extraordinary catalytic activity toward initiation of the thiol-Michael reaction, including thiol-Michael addition-based polymerization, upon visible-light irradiation, leading to a stoichiometric reaction of both thiol and vinyl functional groups. Owing to its features, this visible-light photobase generator enables homogeneous network formation in thiol-Michael polymerizations and also has the potential to be exploited in other visible-light-induced, base-catalyzed thiol-click processes such as thiol-isocynate and thiol-epoxy network-forming reactions.
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