Toward Hybrid Materials: Group Transfer Polymerization of 3-(Trimethoxysilyl)propyl Methacrylate

Front Cover: Group transfer polymerisation (GTP), a living polymerization technique that is easy to scale up, enables the one-pot fabrication of class-II hybrid materials. Specifically a star polymer is synthesized with a 3-(trimethoxy-silyl)propyl methacrylate, alkoxysilane group containing functional monomer. The polymer is then cross-linked to produce an organic-inorganic class-II hybrid material, which can be used in various applications such as thin films and biomaterials. Further details can be found in the article by J. J. Chung, J. R. Jones, and T. K. Georgiou* on page 1806

Liquid–liquid phase separation in aqueous solutions of poly(ethylene glycol) methacrylate homopolymers

Here, the liquid–liquid phase separation (LLPS) in aqueous solutions containing poly(ethylene glycol) (PEG) methacrylate homopolymers is reported for the first time. In this study, the thermoresponse of concentrated solutions of DEGMA60 (two ethylene glycol, EG, groups) TEGMA71 (three EG groups), OEGMA300x (4.5 in average EG groups) of varying molar masses (MM), and OEGMA50028 (nine in average EG groups) is discussed. Interestingly, the temperature of LLPS (TLLPS) is controlled by the length of the PEG side chain, the MM of the OEGMA300x and the polymer concentration. More specifically, the transition temperature decreases with: (i) Decrease in the length of the PEG side chain, (ii) increase in MM of the OEGMA300x, and increase in concentration. In addition, LLPS is also observed in mixtures of OEGMA300x with Pluronic® F127. In conclusion, these systems present a thermally induced LLPS, with the transition temperature being finely tuned to room temperature when DEGMA is used. These systems find potential use in numerous applications, varying from purification to “water-in-water” emulsions

Thermoresponsive block copolymers of increasing architecture complexity: a review on structure-property relationships

Thermogels are an exciting class of stimuli responsive materials with many promising applications ranging from the medical field to additive manufacturing. This review focuses on the structure–property relationship of thermoresponsive block copolymers, with emphasis on the effect of architecture. Polymers based on Pluronic®, N-isopropylacrylamide, oligo(ethylene glycol) (meth)acrylate units, and 2-oxazoline units, which are amongst the most studied thermoresponsive units, are discussed. The effect of the polymer's architecture is crucial for controlling the thermoresponsive properties, such as cloud point and gelation temperature

Tricomponent thermoresponsive polymers based on an amine-containing monomer with tuneable hydrophobicity: Effect of composition

In the present study, six dual-responsive ABC triblock copolymers were synthesised via group transfer polymerisation (GTP) and investigated through visual inspections in terms of their thermoresponsive behaviour. The copolymers consist of i) penta(ethylene glycol) methyl ether methacrylate (PEGMA), which is hydrophilic and thermoresponsive at high temperatures, ii) n-butyl methacrylate (BuMA) as the hydrophobic counterpart to promote self-assembly, and iii) 2-(diethylamino)ethyl methacrylate (DEAEMA), which is pH-responsive by adjusting its hydrophilicity depending on the pH. The effect of the degree of ionisation of DEAEMA units as well as the ionic strength effect on the self-assembly behaviour of the copolymers was tested via dynamic light scattering (DLS). The dissociation constants (pKa) of the amine units of DEAEMA were determined via potentiometric titrations. The thermoresponse has been primarily been investigated in means of cloud points (CPs) at various pH values in deionised water. Detailed phase diagrams were constructed for all the polymer solutions in phosphate buffered saline (PBS), with the interest being focused on the gelation area. It has been clearly proven that gelation is promoted as the content in BuMA and DEAEMA is increased. The polymer that presented the widest gelation area has been further investigated via rheology in terms of its gelation temperature, gelation time and shear-thinning properties

Homopolymer and ABC triblock copolymer mixtures for thermoresponsive gel formulations

Our group has recently invented a novel series of thermoresponsive ABC triblock terpolymers based on oligo(ethylene glycol) methyl ether methacrylate with average Mn 300 g mol−1 (OEGMA300, A unit), n-butyl methacrylate (BuMA, B unit) and di(ethylene glycol) methyl ether methacrylate (DEGMA, C unit) with excellent thermogelling properties. In this study, we investigate how the addition of OEGMA300x homopolymers of varying molar mass (MM) affects the gelation characteristics of the best performing ABC triblock terpolymer. Interestingly, the gelation is not disrupted by the addition of the homopolymers, with the gelation temperature (Tgel) remaining stable at around 30 °C, depending on the MM and content in OEGMA300x homopolymer. Moreover, stronger gels are formed when higher MM OEGMA300x homopolymers are added, presumably due to the homopolymer chains acting as bridges between the micelles formed by the triblock terpolymer, thus, favouring gelation. In summary, novel formulations based on mixtures of triblock copolymer and homopolymers are presented, which can provide a cost-effective alternative for use in biomedical applications, compared to the use of the triblock copolymer only

Thermoresponsive oligo(ethylene glycol) methyl ether methacrylate based copolymers: composition and comonomer effect

Thermoresponsive polymers based on oligo(ethylene glycol) (OEG) methyl ether methacrylate monomers have drawn much attention in recent years. In this investigation, copolymers based on oligo(ethylene glycol) methyl ether methacrylate (OEGMA, 300 g mol-1) and di(ethylene glycol) methyl ether methacrylate (DEGMA) or/and n-butyl methacrylate (n-BuMA) were successfully synthesised via group transfer polymerisation (GTP). The molar mass was kept constant around 10000 g mol-1, while the OEGMA content was varied from 80% w/w to 50% w/w. Three different structures including diblock bipolymer, diblock terpolymer and statistical copolymers were synthesised and compared. The thermoresponsive properties of the copolymers were investigated in deionised water and phosphate buffered saline (PBS), and in aqueous mixtures with Pluronic® F127. Interestingly, while the diblock polymers based on OEGMA and DEGMA were not able to form gel upon heating, they were found to lower the critical gelation concentration (CGC) of Pluronic® F127 from 15% w/w to 10% w/w and increase the gelation temperature from room temperature to near body temperature

Enzyme degradable star polymethacrylate/silica hybrid inks for 3D printing of tissue scaffolds

There is unmet clinical need for scaffolds that can share load with the host tissue while biodegrading under the action of enzymes present at the site of implantation. The aim here was to create the first enzyme cleavable inorganic–organic hybrid “inks” that can be 3D printed as scaffolds for bone regeneration. Inorganic–organic hybrids are co-networks of inorganic and organic components. Although previous hybrids performed well under cyclic loads, there was little control over their degradation. Here we synthesised new hybrids able to degrade in response to endogenous tissue specific metallo proteinases (collagenases) that are involved in natural remodeling of bone. Three well-defined star polymers, of the monomer 3-(trimethoxysilyl)propyl methacrylate (TMSPMA) and of methyl methacrylate (MMA), of different architectures were prepared by RAFT polymerisation. The linear arms were connected together at an enzyme degradable core using a collagenase cleavable peptide sequence (GLY-PRO-LEU-GLY-PRO-LYS) modified with dimethacryloyl groups as a crosslinker for RAFT polymerisation. The effect of polymer architecture, i.e. the position of the TMSPMA groups on the polymers, on bonding between networks, mechanical properties, biodegradation rate and 3D printability, via direct ink writing, was investigated for the first time and was proven to be critical for all three properties. Specifically, hybrids made with star polymers with the TMSPMA close to the core exhibited the best mechanical properties, improved printability and a higher degradation rate

Next generation strategy for tuning the thermoresponsive properties of micellar and hydrogel drug delivery vehicles using ionic liquids

Amongst the greatest challenges in developing injectable controlled thermoresponsive micellar and hydrogel drug delivery vehicles include tuning the cloud point (CP) and reducing the gelation temperature (Tgel), below 37 °C, without compromising stability and solubility. Here, a unique strategy is employed using ionic liquid (IL) matrices to produce stable micellar and hydrogel delivery vehicles of distinct thermoresponsive properties. Each formulation includes the in-house synthesised polymer OEGMA30020-b-BuMA22-b-DEGMA11 with FITC-IgG. Both micellar-IL and hydrogel-IL formulations exhibit enhanced stability following 120 days of storage under 4 °C compared to in phosphate buffered saline (PBS). Visual tests demonstrate that the CP of the micellar-IL carriers can be finely tuned (31- 46 °C). Rheology measurements show that hydrogel strength is significantly increased and Tgel is reduced, from 40 °C in PBS to 30 °C with IL. Finally, a unique stabilisation mechanism is proposed, triggered by the synergetic action of the excipients and IL in each syste

Thermogels based on biocompatible OEGMA-MEGMA diblock copolymers

A series of biocompatible thermoresponsive copolymers were successfully synthesised via group transfer polymerisation (GTP) from methoxy ethylene glycol methacrylate (MEGMA) and methoxy oligo (ethylene glycol) methacrylate (OEGMA, Mn=300 g mol -1). Statistical and diblock copolymers with molar mass around 8100 g mol-1 and various compositions were investigated. Specifically, the content in OEGMA and MEGMA was varied from 80-20, 70-30, 60-40, to 50-50 w/w%. The thermoresponsive and self-assembly behaviour of the copolymers was investigated through visual tests, rheology, dynamic light scattering (DLS) and transmission electron microscopy (TEM). Interestingly, the diblock copolymers with higher MEGMA content were able to form gels at relatively low concentrations (as low as 5% w/w) when increasing the temperature, something that is reported for the first time for linear ethylene glycol based copolymers. A transition of spherical micelle to worm-like micelle was observed in these diblock copolymers that promotes gelation. Furthermore, these in-house synthesised polymers were mixed with Pluronic® F127. It was found that the gelation area of Pluronic® F127 was broadened by the addition of the synthesised copolymers with one formulation, specifically a combination of 12.5% w/w Pluronic® F127 and 12.5% w/w of a statistical OEGMA-co-MEGMA, forming a stable gel from 34°C to 48°C that is a desirable temperature range for biological applications. Finally, cell viability experiments were performed for the three most promising diblock copolymers was investigated and they were confirmed to be non-toxic