Injectable Colloidal Hydrogels of N-Vinylformamide Microgels Dispersed in Covalently Interlinked pH-Responsive Methacrylic Acid-Based Microgels.

Injectable hydrogels offer great potential to augment damaged or degenerated soft tissues. A key criterion for such gels is that their modulus is as close as possible to that of the target tissue. The majority of synthetic hydrogels have used low molecular weight polymer chains which may cause problems if they diffuse away from the injection site and/or increase the local osmotic pressure. We previously introduced a different approach of injecting preformed ultra-high molecular weight pH-responsive microgels (MGs) that interlink to form hydrogels. MGs are crosslinked polymer colloid particles that swell when the pH approaches the particle pKa. These colloidal hydrogels are termed doubly crosslinked microgels (DX MGs). The gel moduli of previous DX MGs were much greater than that reported for human nucleus pulposus (NP) tissue of the spinal intervertebral disk. Here, we replace some of the pH-responsive poly(ethyl acrylate-co-methacrylic acid) (PEA-MAA) MGs with hydrophilic non-ionic MGs based on poly(N-vinylformamide) (NVF). We investigate the morphology and mechanical properties of these new injectable composite DX MGs and show that the mechanical properties can be tuned by systematically varying the NVF MG content. Using this approach, the gel moduli close to that for NP tissue are achieved. These injectable new pH-responsive gels exhibit low cytotoxicity. Our work provides a potential new system for minimally invasive intervertebral disk augmentation.

Highly Stretchable Conductive Covalent Coacervate Gels for Electronic Skin.

Highly stretchable electrically conductive hydrogels have been extensively researched in recent years, especially for applications in strain and pressure sensing, electronic skin, and implantable bioelectronic devices. Herein, we present a new cross-linked complex coacervate approach to prepare conductive hydrogels that are both highly stretchable and compressive. The gels involve a complex coacervate between carboxylated nanogels and branched poly(ethylene imine), whereby the latter is covalently cross-linked by poly(ethylene glycol) diglycidyl ether (PEGDGE). Inclusion of graphene nanoplatelets (Gnp) provides electrical conductivity as well as tensile and compressive strain-sensing capability to the hydrogels. We demonstrate that judicious selection of the molecular weight of the PEGDGE cross-linker enables the mechanical properties of these hydrogels to be tuned. Indeed, the gels prepared with a PEGDGE molecular weight of 6000 g/mol defy the general rule that toughness decreases as strength increases. The conductive hydrogels achieve a compressive strength of 25 MPa and a stretchability of up to 1500%. These new gels are both adhesive and conformal. They provide a self-healable electronic circuit, respond rapidly to human motion, and can act as strain-dependent sensors while exhibiting low cytotoxicity. Our new approach to conductive gel preparation is efficient, involves only preformed components, and is scalable.

Site-Directed Differentiation of Human Adipose-Derived Mesenchymal Stem Cells to Nucleus Pulposus Cells Using an Injectable Hydroxyl-Functional Diblock Copolymer Worm Gel.

Adipose-derived mesenchymal stem cells (ASCs) have been identified for their promising therapeutic potential to regenerate and repopulate the degenerate intervertebral disk (IVD), which is a major cause of lower back pain. The optimal cell delivery system remains elusive but encapsulation of cells within scaffolds is likely to offer a decisive advantage over the delivery of cells in solution by ensuring successful retention within the tissue. Herein, we evaluate the use of a fully synthetic, thermoresponsive poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) (PGMA-PHPMA) diblock copolymer worm gel that mimics the structure of hydrophilic glycosaminoglycans. The objective was to use this gel to direct differentiation of human ASCs toward a nucleus pulposus (NP) phenotype, with or without the addition of discogenic growth factors TGFß or GDF6. Accordingly, human ASCs were incorporated into a cold, free-flowing aqueous dispersion of the diblock copolymer, gelation induced by warming to 37 °C and cell culture was conducted for 14 days with or without such growth factors to assess the expression of characteristic NP markers compared to those produced when using collagen gels. In principle, the shear-thinning nature of the biocompatible worm gel enables encapsulated human ASCs to be injected into the IVD using a 21G needle. Moreover, we find significantly higher gene expression levels of ACAN, SOX-9, KRT8, and KR18 for ASCs encapsulated within worm gels compared to collagen scaffolds, regardless of the growth factors employed. In summary, such wholly synthetic worm gels offer considerable potential as an injectable cell delivery scaffold for the treatment of degenerate disk disease by promoting the transition of ASCs toward an NP-phenotype.

Including fluorescent nanoparticle probes within injectable gels for remote strain measurements and discrimination between compression and tension.

The ability to remotely and non-invasively monitor and measure the strain within injectable gels used to augment soft tissue is highly desirable. Such information could enable real-time monitoring of gel performance and bespoke gel design. We report progress towards this goal using two fluorescent particle probe systems included within two different injectable gels. The two injectable gels have been previously studied in the contexts of intervertebral disc repair and stretchable gels for cartilage repair. The two fluorophore particle probes are blue or near-infrared (NIR) emitting and are present at very low concentrations. The normalised photoluminescence (PL) intensity from the blue emitting probe is shown to equal the compressive deformation ratio of the gels. Furthermore, the normalised ratio of the PL intensities for the blue and NIR probes varies linearly with deformation ratio over a wide range (from 0.2 to 3.0) with a seamless transition from compression to tension. Hence, PL can discriminate between compression and tension. The new approach established here should apply to other gels and enable remote detection of whether a gel is being compressed or stretched as well as the extent. This study may provide an important step towards remotely and minimally invasively measuring the strain experienced by load-supporting gels in vivo.

Core-Shell-Shell Nanoparticles for NIR Fluorescence Imaging and NRET Swelling Reporting of Injectable or Implantable Gels.

Injectable gels that support load are desirable for restoring the mechanical properties of degenerated load-bearing tissue. As these gels become increasingly sophisticated, the need to remotely image them and monitor their swelling increases. However, imaging such gels and monitoring their swelling using noninvasive means is challenging. Here, we use a very low concentration of near-infrared (NIR) core-shell-shell (CSS) reporter nanoparticles to both image and monitor swelling changes of two load-supporting gels. The load-supporting injectable gel consisted of covalently interlinked pH-responsive microgel (MG) particles. The latter gel was not cytotoxic and is termed a doubly cross-linked microgel (DX MG). Inclusion of a complementary fluorescent dye enabled ratiometric monitoring of gel swelling changes in response to pH via nonradiative resonance energy transfer (NRET). In addition, changes in the CSS nanoparticle emission intensity provided a NIR-only method that could also be used to monitor gel swelling. The gel was able to be imaged using NIR light, after being subcutaneously injected into a tissue model. To demonstrate versatility of our approach, CSS and the dye were included within a model implantable gel (poly(acrylamide/acrylic acid)) and fluorescent detection of swelling investigated. Because the concentrations of the reporting species were too low to affect the mechanical properties, our approach to remote gel imaging and swelling monitoring has good potential for application in injectable gels and implants.

Do the properties of gels constructed by interlinking triply-responsive microgels follow from those of the building blocks?

Microgels (MGs) are swellable crosslinked polymer colloids. They can also be used as the only building block to construct nanostructured hydrogels which are denoted as doubly crosslinked microgels (DX MGs). Here, new triply responsive DX MGs comprised of interlinked MGs of oligo(ethylene glycol)methacrylate (OEGMA), 2-(2-methoxyethoxy)ethyl methacrylate (MEO2MA), methacrylic acid (MAA) and a o-nitrobenzyl-based UV photocleavable crosslinker are investigated. The MGs swelled or collapsed in response to temperature and pH changes. These behaviours were rationalised with a generic model using Monte Carlo simulations. The MGs also degraded when UV irradiated due to photocleavage of nPh. DX MGs were assembled from the MGs to give injectable gels that were not cytotoxic to nucleus pulposus cells. Comparison of the responsive properties of the DX MGs and MGs showed that the temperature and pH responses of the former were mostly governed by the latter. However, two key differences were found. Firstly, whilst increasing the crosslinker mol% in the MG building blocks (x) did not change MG particle swelling, the compression modulus (E) and swelling of the DX MG gels were strongly affected by x. The E value for the gels was tuneable using x which is a potentially useful new observation for DX MGs. Secondly, UV irradiation of the DX MGs enhanced gel mechanical photostability in contrast to the behaviour of the MGs. We find that the properties of the DX MGs do not simply follow those of the parent MGs and propose mechanisms to account for the differences. The new family of multi-responsive DX MGs presented in this study have potential application for soft tissue repair as injectable gels or as gel implants which report sterilisation.

Highly deformable hydrogels constructed by pH-triggered polyacid nanoparticle disassembly in aqueous dispersions.

Most hydrogels are prepared using small-molecule monomers but unfortunately this approach may not be feasible for certain biomaterial applications. Consequently, alternative gel construction strategies have been established, which include using covalent inter-linking of preformed gel particles, or microgels (MGs). For example, covalently interlinking pH-responsive MGs can produce hydrogels comprising doubly crosslinked microgels (DX MGs). We hypothesised that the deformability of such DX MGs was limited by the presence of intra-MG crosslinking. Thus, in this study we designed new nanoparticle (NP)-based gels based on pH-swellable NPs that are not internally crosslinked. Two polyacid NPs were synthesised containing methacrylic acid (MAA) and either ethyl acrylate (EA) or methyl methacrylate (MMA). The PMAA-EA and PMAA-MMA NPs were subsequently vinyl-functionalised using glycidyl methacrylate (GMA) prior to gel formation via free-radical crosslinking. The NPs mostly disassembled on raising the solution pH but some self-crosslinking was nevertheless evident. The gels constructed from the EA- and MMA-based NPs had greater breaking strains than a control DX MG. The effect of varying the solution pH during curing on the morphology and mechanical properties of gels prepared using PMAA-MMA-GMA NPs was studied and both remarkable deformability and excellent recovery were observed. The gels were strongly pH-responsive and had tensile breaking strains of up to 420% with a compressive strain-at-break of more than 93%. An optimised formulation produced the most deformable and stretchable gel yet constructed using NPs or MGs as the only building block.

Using microgels to control the morphology and optoelectronic properties of hybrid organic-inorganic perovskite films.

Microgels (MGs) are crosslinked polymer colloid particles that swell in a good solvent. Although MGs have been studied for over 80 years their ability to control the morphology and optoelectronic properties of composite films containing photoactive materials is in its infancy. Solution processable hybrid organic-inorganic perovskites such as CH3NH3PbI3-zClz have attracted enormous fundamental and applied interest because of their outstanding optoelectronic properties. There is considerable interest in establishing methods to control perovskite film morphology, for example, using micropatterning. Here, hydrophilic poly(N-vinylformamide)-based MGs were dispersed in perovskite precursor solution which was then spin coated to deposit CH3NH3PbI3-zClz/MG films for the first time. Remarkably, the CH3NH3PbI3-zClz/MG composites formed disordered inverse opal (DIO) films. The CH3NH3PbI3-zClz/MG composition ranges which gave DIO films are identified using a phase diagram. The pore wall thickness is shown to be controlled by the volume fraction of MGs used and a simple model is presented to explain this behaviour. The MGs not only caused CH3NH3PbI3-zClz to be more efficiently deposited but also increased light absorption and photoluminescence intensity. Demonstration solar cells constructed containing the DIO CH3NH3PbI3-zClz/MG films had an average conversion efficiency of 6.58 ± 0.81%. A mechanism for DIO film formation is discussed. The principles established in this study wherein MGs control the morphology and properties of CH3NH3PbI3-zClz/MG films should also apply to other perovskite/MG composites.

Surface structure, optoelectronic properties and charge transport in ZnO nanocrystal/MDMO-PPV multilayer films.

Blends of semiconducting nanocrystals and conjugated polymers continue to attract major research interest because of their potential applications in optoelectronic devices, such as solar cells, photodetectors and light-emitting diodes. In this study we investigate the surface structure, morphological and optoelectronic properties of multilayer films constructed from ZnO nanocrystals (NCs) and poly[2-methoxy-5-(3',7'-dimethyloctyloxy)-1,4-phenylenevinylene] (MDMO-PPV). The effects of layer number and ZnO concentration (CZnO) used on the multilayer film properties are investigated. An optimised solvent blend enabled well-controlled layers to be sequentially spin coated and the construction of multilayer films containing six ZnO NC (Z) and MDMO-PPV (M) layers (denoted as (ZM)6). Contact angle data showed a strong dependence on CZnO and indicated distinct differences in the coverage of MDMO-PPV by the ZnO NCs. UV-visible spectroscopy showed that the MDMO-PPV absorption increased linearly with the number of layers in the films and demonstrates highly tuneable light absorption. Photoluminescence spectra showed reversible quenching as well as a surprising red-shift of the MDMO-PPV emission peak. Solar cells were constructed to probe vertical photo-generated charge transport. The measurements showed that (ZM)6 devices prepared using CZnO = 14.0 mg mL-1 had a remarkably high open circuit voltage of ∼800 mV. The device power conversion efficiency was similar to that of a control bilayer device prepared using a much thicker MDMO-PPV layer. The results of this study provide insight into the structure-optoelectronic property relationships of new semiconducting multilayer films which should also apply to other semiconducting NC/polymer combinations.

Pickering Emulsions Stabilized by pH-Responsive Microgels and Their Scalable Transformation to Robust Submicrometer Colloidoisomes with Selective Permeability.

Colloidosomes are micrometer-sized hollow particles that have shells consisting of coagulated or fused colloid particles. While many large colloidosomes with sizes well above 1.0 µm have been prepared, there are fewer examples of submicrometer colloidosomes. Here, we establish a simple emulsion templating-based method for the preparation of robust submicrometer pH-responsive microgel colloidosomes. The colloidosomes are constructed from microgel particles based on ethyl acrylate and methacrylic acid with peripheral vinyl groups. The pH-responsive microgels acted as both a Pickering emulsion stabilizer and macro-cross-linker. The emulsion formation studies showed that the minimum droplet diameter was reached when the microgel particles were partially swollen. Microgel colloidosomes were prepared by covalently interlinking the microgels adsorbed at the oil-water interface using thermal free-radical coupling. The colloidosomes were prepared using a standard high-shear mixer with two different rotor sizes that corresponded to high shear (HS) and very high shear (VHS) mixing conditions. The latter enabled the construction of submicrometer pH-responsive microgel-colloidosomes on the gram scale. The colloidosomes swelled strongly when the pH increased to above 6.0. The colloidosomes were robust and showed no evidence of colloidosome breakup at high pH. The effect of solute size on shell permeation was studied using a range of FITC-dextran polymers, and size-selective permeation occurred. The average pore size of the VHS microgel-colloidosomes was estimated to be between 6.6 and 9.0 nm at pH 6.2. The microgel-colloidosome properties suggest that they have the potential for future applications in cosmetics, photonics, and delivery.

Self-assembly of poly(lauryl methacrylate)-b-poly(benzyl methacrylate) nano-objects synthesised by ATRP and their temperature-responsive dispersion properties.

Self-assembling poly(lauryl methacrylate)-b-poly(benzyl methacrylate) (PLMAx-PBzMAy) diblock copolymers were synthesised for the first time using solution atom transfer radical polymerisation (ATRP). The PLMA degree of polymerisation (x) was fixed at 14 and the PBzMA degree of polymerisation (y) was varied from 34 to 74. Post-polymerisation transfer of this new series of diblock copolymers from chloroform into n-dodecane (a poor solvent for PBzMA) resulted in self-assembly of polymeric nano-objects. The morphologies for the latter (spheres, worms and vesicles) were controlled by y. The observed morphologies generally agreed with those reported for related PLMAx-PBzMAy diblock copolymers (x ≥ 16) prepared by polymerisation induced self-assembly (PISA) via reversible addition-fragmentation chain transfer (RAFT) polymerisation (Fielding et al., J. Am. Chem. Soc., 2014, 136, 5790). However, a number of differences were observed such as de-gelation behaviour and the phase boundary positions compared to those expected from Fielding et al. Variable-temperature dynamic light scattering studies for the PLMA14-PBzMA34 spheres revealed that the aggregation number was unaffected by a temperature increase over the range of 20-90 °C, which differed markedly from the behaviour observed for PLMA14-PBzMA64 worms. This difference is a new observation with mechanistic importance for the worm-to-sphere breakdown mechanism. We show that concentrated PLMA14-PBzMAy dispersions (20% w/w) in n-dodecane can be prepared using post-polymerisation transfer. The dispersion with a mixed spherical and worm-like copolymer phase exhibited reversible de-gelation when heated. Surprisingly, the dispersions containing only the worm phase remained as gels (which were white) at temperatures up to 90 °C. Our new ATRP approach for preparing temperature-responsive non-aqueous nano-object dispersions presented here decoupled chain growth and self-assembly and will apply to other copolymer dispersions.

Synthesis of polyacid nanogels: pH-responsive sub-100 nm particles for functionalisation and fluorescent hydrogel assembly.

Nanogels are crosslinked polymer particles with a swollen size between 1 and 100 nm. They are of major interest for advanced surface coatings, drug delivery, diagnostics and biomaterials. Synthesising polyacid nanogels that show triggered swelling using a scalable approach is a key objective of polymer colloid chemistry. Inspired by the ability of polar surfaces to enhance nanoparticle stabilisation, we report the first examples of pH-responsive polyacid nanogels containing high -COOH contents prepared by a simple, scalable, aqueous method. To demonstrate their functionalisation potential, glycidyl methacrylate was reacted with the -COOH chemical handles and the nanogels were converted to macro-crosslinkers. The concentrated (functionalised) nanogel dispersions retained their pH-responsiveness, were shear-thinning and formed physical gels at pH 7.4. The nanogels were covalently interlinked via free-radical coupling at 37 °C to form transparent, ductile, hydrogels. Mixing of the functionalised nanogels with polymer dots enabled covalent assembly of fluorescent hydrogels.

How gold nanoparticles can be used to probe the structural changes of a pH-responsive hydrogel.

Gold nanoparticles (GNPs) have UV-visible absorption spectra that are highly sensitive to their local environment due to their surface plasmon resonance (SPR). Furthermore, GNPs are able to quench the fluorescence of suitable dyes depending on the GNP-dye separation. Both of these features have led to the use of GNPs as spectroscopic rulers. In this study we sought to use GNPs as spectroscopic probes to investigate the local structural changes associated with the macroscopic pH-triggered swelling/de-swelling transitions of a pH-responsive hydrogel. The hydrogel used in this study comprised covalently inter-linked pH-responsive poly(ethylacrylate-co-methacrylic acid-co-divinyl benzene) microgel particles (MGs). MGs are crosslinked polymer colloids that swell when the pH approaches the pKa of the constituent polymer. The interlinked MG hydrogels are termed doubly crosslinked microgels (DX MGs) and are a new family of hydrogels. They had polymer volume fractions (ϕp) that strongly decreased as the pH increased. UV-visible spectra showed that the wavelength of the SPR absorption (λmax) for the DX MG/GNP gels was pH-responsive. A linear relationship was found between λmax and ϕp for ϕp values up to ∼0.80. The inclusion of Rhodamine 6G within the DX MG/GNP hydrogels resulted in metal-induced fluorescence quenching which was studied using photoluminescence (PL) spectroscopy. The extent of quenching was pH-dependent and was also proportional to ϕp. The results of the study showed that the pH-triggered changes of the nanoscale and macroscopic swelling for the DX MGs were similar and imply that affine swelling occurred, which is a new observation. The data suggest that UV-visible or PL spectroscopy could be used to study the swelling of pH-responsive hydrogels containing GNPs remotely.

Textured ZnO films from evaporation-triggered aggregation of nanocrystal dispersions and their use in solar cells.

Due to its high electron mobility, good stability and potential for low-temperature synthesis ZnO has received considerable attention for use in solar cells, photodetectors and sensors. Whilst there have been reports involving the formation ZnO films with porous morphologies the majority of those have involved elaborate or time-consuming preparation methods. In this study we investigate a simple new method for preparing textured porous ZnO (tp-ZnO) films. We used colloidal instability triggered by the evaporation of a volatile stabilising ligand during spin-coating of a ZnO nanocrystal (NC) dispersion to deposit crack-free tp-ZnO films. The porosity of the tp-ZnO films was 56% and they could be prepared using amine-based ligands with boiling points less than or equal to 78 °C. To demonstrate the ability to use the tp-ZnO films as electron acceptors they were infiltrated with poly(3-hexylthiophene) (P3HT) and solar cells prepared. The power conversion efficiencies of the tp-ZnO/P3HT devices reached values that were three times higher than a control bilayer ZnO/P3HT device prepared using a sol-gel derived ZnO film. Because our method used a low temperature treatment and ZnO films are used in a wide variety of third-generation solar cells, the new tp-ZnO films introduced here may offer a low cost method for improving the efficiency of other solar cells.

CH3NH3PbI3 films prepared by combining 1- and 2-step deposition: how crystal growth conditions affect properties.

Perovskite solar cells continue to attract strong attention because of their unprecedented rate of power conversion efficiency increase. CH3NH3PbI3 (MAPbI3) is the most widely studied perovskite. Typically one-step (1-s) or two-step (2-s) deposition methods are used to prepare MAPbI3 films. Here, we investigate a new MAPbI3 film formation method that combines 1-s and 2-s deposition (termed 1 & 2-s) and uses systematic variation of the stoichiometric mole ratio (x) for the PbI2 + xMAI solutions employed. The PbI2 + xMAI solutions were used to deposit precursor films that were subsequently dipped in MAI solution as a second step to produce the final MAPbI3 films. The morphologies of the 1 & 2-s MAPbI3 films consisted of three crystal types: tree-like microcrystals (≫1 µm), cuboid meso-crystals (∼0.1-1 µm) and nanocrystals (∼50-80 nm). Each crystal type and their proportions were controlled by the value for x. The new 1 & 2-s deposition method produced MAPbI3 films with tuneable optoelectronic properties that were related to those for the conventional 1-s and 2-s films. However, the 1 & 2-s film properties were not simply a combination of those for the 1-s and 2-s films. The 1 & 2-s films showed enhanced light scattering and the photoluminescence spectra displayed a morphologically-dependent red-shift. The unique morphologies for the 1 & 2-s films also strongly influenced PbI2 conversion, power conversion efficiency, hysteresis and recombination. The trends for the performance parameters and hysteresis were compared for devices constructed using spiro-MeOTAD and P3HT and were similar. The 1 & 2-s method should apply to other perovskite formulations and the new insights concerning MAPbI3 crystal growth conditions, morphology and material properties established in this study should also be transferable.

Hydrogel Composites Containing Sacrificial Collapsed Hollow Particles as Dual Action pH-Responsive Biomaterials.

In this study hydrogel composites are investigated that contain sacrificial pH-responsive collapsed hollow particles (CHPs) entrapped within a poly(acrylamide) (PAAm) network. The CHPs were prepared using a scalable (mainly) water-based method and had a bowl-like morphology that was comparable to that of red blood cells. The CHPs were constructed from poly(methyl methacrylate-co-methacrylic acid), which is a pH-responsive copolymer. The PAAm/CHP composite morphology was probed with optical microscopy, CLSM and SEM. These data showed the CHPs were dispersed throughout the PAAm network. Inclusion of the CHPs within the gel composites increased the modulus in a tunable manner. The CHPs fragmented at pH values greater than the pKa of the particles, and this process decreased the gel modulus to values similar to that of the parent PAAm hydrogel. CHPs containing a model drug were used to demonstrate pH-triggered release from PAAm/CHP and the release kinetics obeyed Fickian diffusion. The composite gels had low cytotoxicity as evidenced by Live/Dead and MTT assays. The hydrogel composites showed dual action pH-triggered softening with simultaneous drug release which occurred without a volume increase. The hydrogel composites may have potential application as enteric gels or for intra-articular drug delivery.

Factors Affecting Peptide Interactions with Surface-Bound Microgels.

Effects of electrostatics and peptide size on peptide interactions with surface-bound microgels were investigated with ellipsometry, confocal microscopy, and atomic force microscopy (AFM). Results show that binding of cationic poly-L-lysine (pLys) to anionic, covalently immobilized, poly(ethyl acrylate-co-methacrylic acid) microgels increased with increasing peptide net charge and microgel charge density. Furthermore, peptide release was facilitated by decreasing either microgel or peptide charge density. Analogously, increasing ionic strength facilitated peptide release for short peptides. As a result of peptide binding, the surface-bound microgels displayed pronounced deswelling and increased mechanical rigidity, the latter quantified by quantitative nanomechanical mapping. While short pLys was found to penetrate the entire microgel network and to result in almost complete charge neutralization, larger peptides were partially excluded from the microgel network, forming an outer peptide layer on the microgels. As a result of this difference, microgel flattening was more influenced by the lower Mw peptide than the higher. Peptide-induced deswelling was found to be lower for higher Mw pLys, the latter effect not observed for the corresponding microgels in the dispersed state. While the effects of electrostatics on peptide loading and release were similar to those observed for dispersed microgels, there were thus considerable effects of the underlying surface on peptide-induced microgel deswelling, which need to be considered in the design of surface-bound microgels as carriers of peptide loads, for example, in drug delivery or in functionalized biomaterials.

Composite hydrogels of polyacrylamide and crosslinked pH-responsive micrometer-sized hollow particles.

Whilst hydrogels and hollow particles both continue to attract much attention in the literature there are few examples of hydrogel composites containing hollow particles. Here, we study composite polyacrylamide (PAAm) hydrogels containing micrometer-sized pH-responsive shell-crosslinked hollow particles (abbreviated as HPXL) based on poly(methylmethacrylate-co-methacrylic acid) functionalised with glycidyl methacrylate (GMA). The HPXL particles were prepared using our scaleable emulsion template method and inclusion of GMA was found to promote spherical hollow particle formation. The pendant vinyl groups from GMA enabled shell-crosslinked hollow particles to be prepared prior to formation of the PAAm/HPXL composite gels. The morphologies of the particles and composite gels were studied by optical microscopy, confocal laser scanning microscopy and scanning electron microscopy. Dynamic rheology measurements for the composite gels showed that the modulus variation with HPXL concentration could be described by a percolation model with a HPXL percolation threshold concentration of 4.4 wt% and a scaling exponent of 2.6. The composite gels were pH-responsive and largely maintained their mechanical properties over the pH range 4.0 to 8.0. Because the composite gels had tuneable mechanical properties (with modulus values up to 530 kPa) and were pH-responsive they are potential candidates for future wound healing or membrane applications.

Using intra-microgel crosslinking to control the mechanical properties of doubly crosslinked microgels.

Microgels (MGs) are crosslinked polymer particles that swell when the pH approaches the pKa of the constituent polymer. Our earlier work showed that concentrated MG dispersions can be covalently interlinked to form macroscopic hydrogels, which are termed doubly crosslinked microgels (DX MGs). Here, we study for the first time the effects of intra-MG crosslinking on the swelling of the MGs and the mechanical properties of the DX MGs. The MGs were synthesised by emulsion copolymerisation of ethyl acrylate (EA) or methacrylic acid (MAA) and divinylbenzene (DVB). The latter was a crosslinking monomer. For comparison, MGs were prepared where DVB was replaced by either 1,4-butanediol diacrylate (BDDA) or a 1 : 1 mixture of both DVB and BDDA. The MG swelling behaviours were studied by dynamic light scattering; whereas, the DX MG mechanical properties were studied by dynamic rheology and uniaxial compression measurements. Inclusion of DVB within the MGs resulted in both highly swelling MGs and highly ductile DX MGs. The average strain-at-break value for the DVB-containing DX MGs was 76% which represents the highest value yet reported for a DX MG prepared using commercially available monomers. It was also shown that good tuneability of the DX MG properties could be obtained simply by controlling the DVB and BDDA contents within the MG particles. Analysis of the swelling and compression data enabled relationships between the volume-swelling ratio of the MGs and either the modulus or strain-at-break values for the DX MGs. These relationships also applied to a DVB-free system prepared with a low BDDA content. An interesting conclusion from this study is that the DX MGs can be thought of mechanically as macroscopic MG particles. The results of this study provide design tools for improving DX MG ductility and hence increasing the range of potential applications for this new class of hydrogel.

A study of conductive hydrogel composites of pH-responsive microgels and carbon nanotubes.

Conductive gel composites are attracting considerable attention because of their interesting electrical and mechanical properties. Here, we report conductive gel composites constructed using only colloidal particles as building blocks. The composites were prepared from mixed dispersions of vinyl-functionalised pH-responsive microgel particles (MGs) and multi-walled carbon nanotubes (CNTs). MGs are crosslinked pH-responsive polymer colloid particles that swell when the pH approaches the pKa of the particles. Two MG systems were used which contained ethyl acrylate (EA) or methyl acrylate (MA) and around 30 mol% of methacrylic acid (MAA). The MA-based MG is a new pH-responsive system. The mixed MG/CNT dispersions formed thixotropic physical gels. Those gels were transformed into covalent interlinked electrically conducting doubly crosslinked microgel/CNT composites (DX MG/CNT) by free-radical reaction. The MGs provided the dual roles of dispersant for the CNTs and macro-crosslinker for the composite. TEM data showed evidence for strong attraction between the MG and the CNTs which facilitated CNT dispersion. An SEM study confirmed CNT dispersion throughout the composites. The mechanical properties of the composites were studied using dynamic rheology and uniaxial compression measurements. Surprisingly, both the ductility and the modulus of the gel composites increased with increasing CNT concentration used for their preparation. Human adipose-derived mesenchymal stem cells (AD-MSCs) exposed to DX MG/CNT maintained over 99% viability with metabolic activity retained over 7 days, which indicated non-cytotoxicity. The results of this study suggest that our approach could be used to prepare other DX MG/CNT gel composites and that these materials may lead to future injectable gels for advanced soft-tissue repair.