Composite hydrogels with temperature sensitive heterogeneities: influence of gel matrix on the volume phase transition of embedded poly-(N-isopropylacrylamide) microgels

The thermo-responsive behaviour of poly-(N-isopropylacrylamide) (PNiPAM) microgels embedded in covalently cross-linked non-temperature-sensitive polyacrylamide (PAam) hydrogel matrixes with different compositions was investigated by using small angle neutron scattering (SANS). The composition of the composite hydrogel was varied by (a) increasing the cross-linker and acrylamide concentration leading to strong hydrogel matrixes and (b) by increasing the microgel concentration to obtain composite gels with an internal structure. Additionally we synthesized composite hydrogels by using γ-irradiation as initiation for the polymerisation. This leads to the formation of chemical bonds between the PNiPAM microgels and the surrounding polyacrylamide matrix. Thus it is possible to synthesize hydrogels without an additional cross-linker, as well as pure particle networks. Some samples were prepared at two different temperatures, below and above the volume phase transition temperature of PNiPAM, resulting in highly swollen or totally collapsed microgels during the incorporation step. The volume phase transition of microgels is not influenced by a hydrogel matrix with high acrylamide concentration independent of the preparation temperature. However, an increased cross-linker concentration leads to a corset like constraint on microgel swelling. Microgels, which are embedded in the collapsed state (at 50 °C), are not able to swell upon cooling, whereas microgels embedded in the swollen state can collapse upon heating. For samples with an increased microgel concentration, the close microgel packing was disturbed by the formation of the polyacrylamide matrix. The hydrogel matrix squeezes the microgels together and leads to partial aggregation. The experiments demonstrate how composite hydrogels with stimuli-sensitive heterogeneities can be prepared such that the full responsiveness of the embedded microgels is retained while the macroscopic dimensions of the gel are not affected by the volume phase transition of the microgels.     

Unperturbed volume transition of thermosensitive poly-(N-isopropylacrylamide) microgel particles embedded in a hydrogel matrix

The thermoresponsive behavior of poly-(N-isopropylacrylamide) (PNiPAM) microgels embedded in a covalently cross-linked polyacrylamide hydrogel matrix was investigated using ultraviolet-visible (UV-vis) spectroscopy, small-angle neutron scattering (SANS), and confocal laser scanning microscopy. The hydrogel synthesis was performed at two different temperatures, below and above the volume phase transition temperature of PNiPAM, resulting in highly swollen or fully collapsed PNiPAM microgel particles during the incorporation step. UV-vis spectroscopy experiments verify that the incorporation of thermosensitive microgels leads to temperature-sensitive optical properties of the composite materials. SANS measurements at different temperatures show that the thermosensitive swelling behavior of the PNiPAM microgels is fully retained in the composite material. Volume and structure criteria of the embedded microgel particles are compared to those of the free microgels in acrylamide solution. To visualize the temperature responsive behavior of larger PNiPAM particles, confocal fluorescence microscopy images of PNiPAM beads, of 40-microm size, were taken at two different temperatures. The micrographs also demonstrate the retained temperature sensitivity of the embedded microgels.     

微凝胶增强两性复合水凝胶的制备与性能

将核壳微凝胶包埋在两性基质中,制备了复合水凝胶(CAH)。 研究发现,利用微凝胶与聚合物链之间的物理缠结作用,可以使复合凝胶具有致密的网络结构,力学性能显著提高;复合凝胶对pH和离子强度敏感,呈现出典型的两性聚电解质凝胶的溶胀行为。 同时微凝胶的存在和特殊的复合结构,可赋予CAH两性凝胶基质所不具有的响应性,并实现在高温下快速响应。     

Injectable Supramolecular Hydrogel/Microgel Composites for Therapeutic Delivery

Shear‐thinning hydrogels are useful for biomedical applications, from 3D bioprinting to injectable biomaterials. Although they have the appropriate properties for injection, it may be advantageous to decouple injectability from the controlled release of encapsulated therapeutics. Toward this, composites of hydrogels and encapsulated microgels are introduced with microgels that are fabricated via microfluidics. The microgel cross‐linker controls degradation and entrapped molecule release, and the concentration of microgels alters composite hydrogel rheological properties. For the treatment of myocardial infarction (MI), interleukin‐10 (IL‐10) is encapsulated in microgels and released from composites. In a rat model of MI, composites with IL‐10 reduce macrophage density after 1 week and improve scar thickness, ejection fraction, cardiac output, and the size of vascular structures after 4 weeks when compared to saline injection. Improvements are also observed with the composite without IL‐10 over saline, emphasizing the role of injectable hydrogels alone on tissue repair.     

Plum-pudding gels as a platform for drug delivery: understanding the effects of the different components on the diffusion behavior of solutes

The internal structure of composite gels made of responsive microgel particles inserted into a bulk hydrogel (N-isopropylacrylamide microgel particles in a cross-linked dimethylacrylamide matrix) has been investigated from the diffusion behavior of poly(ethylene glycol) (PEG) probes through the network, in the absence of specific interactions between the diffusing molecules and the system. The effect of the different components has been examined, for example, the size of the probe, the bulk structure, and the microgel nature. Particles were characterized prior to their insertion into the hydrogel in order to describe their properties as a function of size and cross-linker content, thus revealing different swelling behaviors. The biggest effects on the diffusion of the PEG probes were related to the bulk structure, and no major effects were registered by the addition of different microgels into the hydrogel network. We attempt to rationalize this behavior in terms of the composite gel structure and discuss the results in terms of their meaning for controlled drug delivery strategies.     

Fabrication of Thermo‐Responsive Hybrid Hydrogels by In‐Situ Mineralization and Self‐Assembly of Microgel Particles

Summary: An in‐situ mineralization process in the presence of thermo‐responsive microgels leads to the formation of well‐defined hybrid materials. Experimental data suggest that control of the mineralization process in the presence of the microgels offers the possibility to obtain sub‐micrometer‐sized hybrid particles or macroscopic hybrid hydrogels. The rapid formation of CaCO₃ crystals in the microgel structure favors the preparation of the hybrid particles wherein inorganic crystals cover the shell layer of the microgel. The slow formation of CaCO₃ crystals leads to the simultaneous self‐assembly of the microgel particles on the bottom of the reaction vessel, and the formation of a physical network. It has been demonstrated that hybrid hydrogel materials with different calcium carbonate contents and temperature‐dependent swelling‐deswelling properties can be prepared.

Formation of a hybrid hydrogel by the vapor diffusion method.     

Switchable Bifunctional Stimuli‐Triggered Poly‐N‐Isopropylacrylamide/DNA Hydrogels

DNA‐tethered poly‐N‐isopropylacrylamide copolymer chains, pNIPAM, that include nucleic acid tethers have been synthesized. They are capable of inducing pH‐stimulated crosslinking of the chains by i‐motif structures or to be bridged by Ag⁺ ions to form duplexes. The solutions of pNIPAM chains undergo crosslinking at pH 5.2 or in the presence of Ag⁺ ions to form hydrogels. The hydrogels reveal switchable hydrogel‐to‐solution transitions by the reversible crosslinking of the chains at pH 5.2 and the separation of the crosslinking units at pH 7.5, or by the Ag⁺ ion‐stimulated crosslinking of the chains and the reverse dissolution of the hydrogel by the cysteamine‐induced elimination of the Ag⁺ ions. The DNA‐crosslinked hydrogels are thermosensitive and undergo reversible temperature‐controlled hydrogel‐to‐solid transitions. The solid pNIPAM matrices are protected against the OH^? or cysteamine‐stimulated dissociation to the respective polymer solutions.     

Lead‐sensitive PNIPAM microgels modified with crown ether groups

A series of lead‐sensitive poly(N‐isopropylacrylamide) microgels with pendant crown ether groups were prepared. Their cation‐sensitive behaviors were studied by dynamic light scattering. When ionic strength is not controlled, adding salts causes the microgel particles to deswell. However, when the salt effect is ruled out by keeping a constant ionic strength, adding Pb²⁺ results in much larger swelling. The Pb²⁺‐induced swelling was explained by the formation of host–guest complex between Pb²⁺ and the pendant crown ether groups, which increases the hydrophilicity of the polymer and accordingly the degree of swelling. The lead sensitivity of the microgels increases with increasing crown ether content. For the modified microgel with the highest crown ether content, it swells to ～430% of its original volume at [Pb²⁺] = 10 mM. Other cations also increase the swelling degree of the modified microgels. The extent of the cation‐induced swelling mainly depends on their affinity to the pendant crown ether groups. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 4120–4127, 2010     

Equilibrium and kinetic aspects of the uptake of poly(ethylene oxide) by copolymer microgel particles of N-isopropylacrylamide and acrylic acid

The use of microgels for controlled uptake and release has been an area of active research for many years. In this work copolymer microgels of N-isopropylacrylamide (NIPAM) and acrylic acid (AAc), containing different concentrations of AAc and also cross-linking monomer, have been prepared and characterized. These microgels are responsive to pH and temperature. As well as monitoring the equilibrium response to changes in these variables, the rates of swelling/de-swelling of the microgel particles, on changing either the pH or the temperature, have also been investigated. It is shown that the rate of de-swelling of the microgel particles containing AAc is much faster than the rate of swelling, on changing the pH appropriately. This is explained in terms of the relative mobilities of the H(+) and Na(+) ions, in and out of the particles. It was observed that the microgels containing AAc, at pH 8, de-swelled relatively slowly on heating to 50 degrees C from 20 degrees C. This is attributed to the resistance to collapse associated with the large increase in counterion concentration inside the microgel particles. The swelling and de-swelling properties of these copolymer microgels have also been investigated in aqueous poly(ethylene oxide) (PEO) solutions, of different MW (2000-300 000). The corresponding absorbed amounts of PEO from solution onto the microgels have also been determined using a depletion method. The results, as a function of AAc content, cross-linker concentration, PEO MW, pH, and temperature, have been rationalized in terms of the ease and depth of penetration of the PEO chains into the various microgel particles and also the H-bonding associations between PEO and either the -COOH of the AAc moeities and/or the H of the amide groups (much weaker). Finally, the adsorption and desorption of the PEO molecules in to and out of the microgel particles have been shown to be extremely slow compared to normal diffusion time scales for polymer adsorption onto rigid surfaces.     

Decoupled Thermo‐ and pH‐Responsive Hydrogel Microspheres Cross‐Linked by Rotaxane Networks

Rotaxane cross‐linked (RC) microgels that exhibit a decoupled thermo‐ and pH‐responsive volume transition were developed. The pH‐induced changes of the aggregation/disaggregation states of cyclodextrin in the RC networks were used to control the swelling capacity of the entire microgels. Different from conventional thermo‐ and pH‐responsive microgels, which are usually obtained from copolymerizations involving charged monomers, the RC microgels respond to temperature as intended, even in the presence of charged functional molecules such as dyes in the microgel dispersion. The results of this study should lead to new applications, including drug delivery systems that require a retention of their smart functions even in environments that may contain foreign ions, for example, in in vivo experiments.     

Preparation of a novel pH-responsive silver nanoparticle/poly(HEMA-PEGMA-MAA) composite hydrogel

In this paper, series of novel pH-responsive silver (Ag) nanoparticle/poly(2-hydroxyethyl methacrylate (HEMA)-poly(ethylene glycol) methyl ether methacrylate (PEGMA)-methacrylic acid (MAA)) composite hydrogel were successfully prepared by in situ reducing Ag⁺ ions anchored in the hydrogel by the deprotonized carboxyl acid groups. X-ray diffraction (XRD), UV-vis spectrophotometry, transmission electron microscopy (TEM) and electric conductivity tests were used to characterize the composite system. It was found that the size and morphology of the reduced Ag nanoparticles in the composite hydrogels could be changed by loading the Ag⁺ ions at various swelling ratios of hydrogel. Moreover, compared to the pure poly(HEMA-PEGMA-MAA) hydrogel, not only did the Ag nanoparticle/poly(HEMA-PEGMA-MAA) composite hydrogels exhibit much higher swelling ratio and faster deswelling rate, but also higher pH switchable electrical properties upon controlling the interparticle distance under pH stimulus. The pH responsive nanocomposite hydrogel reported here might be a potentially smart material in the range of applications including electronics, biosensors and drug-delivery devices.     

葡萄糖敏感微凝胶的溶胀动力学研究

通过沉淀聚合法合成了P(NIPAM-co-AA)微凝胶,然后在EDC催化下用3-氨基苯硼酸对微凝胶进行改性,制备了P(NIPAMI-co-AAPBA)微凝胶.红外光谱检测证明改性完全.改性后的微凝胶仍具有很好的温敏性,但由于引入疏水的苯硼酸基团,微凝胶的体积相转变温度大大降低.P(NIPAM-co-AAPBA)微凝胶具...     

Physicochemical characterization and drug release properties of PDMAEMA/OSA Semi‐IPN hydrogels with microporous structure

A new poly(2‐(dimethylamino) ethyl methacrylate)/oxidized sodium alginate (PDMAEMA) semi‐interpenetrating network (Semi‐IPN) hydrogel with microporous structure was prepared by using PDMAEMA microgels as an additive during the polymerization/crosslinking process. The interior morphology characterized by scanning electron microscopy showed the Semi‐IPN hydrogels have different pore sizes by changing the amount of microgels. The hydrogels were also characterized by using Fourier transform infrared and DSC. The swelling behaviors of hydrogels indicated that the hydrogels have excellent pH and temperature sensitivity. Bovine serum albumin was entrapped in the hydrogels and the in vitro drug release profiles were established in different buffer solutions at various temperatures. The release behaviors of the model drug were dependent on the pore size of the hydrogels and environmental temperature/pH, which suggested that these materials have potential application as intelligent drug carriers. Copyright © 2011 John Wiley & Sons, Ltd.     

Functionalised Microgels for Acrylic Coatings

Summary: Aqueous acrylic dispersions of hydroxy-functionalised copolymer microgel particles crosslinked with allyl methacrylate were synthesized by emulsion polymerization. The microgels were investigated as reactive polymer fillers in mixtures with a water-borne film-forming dispersion. Properties of coatings cast from mixtures of aqueous dispersion of hard microgel particles and film-forming water-borne dispersion were investigated. The swelling behaviour of microgels in selected solvents (aliphatic ketones) as a function of microgel composition is discussed as well. It was found that the swelling ability of microgels decreased with growing degree of crosslinking. Microgels comprising copolymerised butyl methacrylate swelled less in aliphatic ketones than microgels without this comonomer. This work was focused mainly on the influence of microgels incorporated in the commercial solvent-borne acrylic binders on the properties of coatings. It was shown that the application of microgels that were redispersed in acetone did not affect the surface appearance and transparency of coatings. Moreover, the presence of microgel network precursors accelerated film curing at ambient temperature and improved the final hardness of coatings.     

聚富马酸丙二醇酯/羟基磷灰石复合多孔水凝胶的制备及其矿化性能研究

采用二步法合成了可降解的聚富马酸丙二醇酯(poly(propylene fumarate),PPF),并和N-乙烯基吡咯烷酮(N-vinyl pyrrolidone,NVP)共聚,以1,4-二氧六环为溶剂,通过改变溶剂的量制备了溶胀性能不同的PPF水凝胶.采用万能力学测试仪和扫描电子显微镜分别表征了水凝胶的压缩模量和形貌结构.选择20％ PPF和10％ NVP的聚合体系,预掺3％的纳米羟基磷灰石(hydroxyapatite,HA),以氯化钠粒子为致孔剂,制备了孔径在280～450 μm的纳米复合多孔水凝胶,使其压缩模量提高了61％.模拟体液矿化10天的结果显示,磷灰石成核位点的存在和良好的与外界液体环境物质交换的能力,促进了多孔水凝胶表面磷灰石的沉积,说明HA的复合可以有效提高PPF多孔水凝胶的成骨活性.     

Conducting hydrogels based on semi‐interpenetrating networks of polyaniline in poly(acrylamide‐co‐itaconic acid) matrix: synthesis and characterization

In this work, acrylamide/itaconic acid copolymeric hydrogels are prepared by free radical polymerization initiated by redox initiators of potassium persulfate and N ,N ,N ′,N ′‐tetramethyl ethylene diamine; N ,N ′methylene bisacrylamide was employed as a crosslinking agent. Aniline monomer was absorbed in the network of poly(acrylamide‐co‐itaconic acid) P(AAm‐co‐IA) hydrogel and followed by gamma radiation induced polymerization at room temperature. The novel semi‐interpenetrating network was comprised of linear polyaniline immersed in P(AAm‐co‐IA) matrix. Electrical conductivity of the hydrogels was measured using four‐probe technique. The conductivities for the prepared hydrogels are found to increase from 5.5 × 10^?7 S cm^?1 for P(AAm‐co‐IA) alone to 4.4 × 10^?3 S cm^?1 for semi‐interpenetrating polymer network P(AAm‐co‐IA)/polyaniline. Thus, a new composite hydrogel with good conductive properties also displaying enhanced mechanical strength and pH sensitivity was prepared. Copyright © 2017 John Wiley & Sons, Ltd.     

Preparation of Poly(N‐isopropylacrylamide) Microgels using Different Initiators Under Various pH Values

Ammonium persulfate (APS), 2,2′‐azobis(amidinopropane) dihydrochloride (V50) and 4,4′‐azobis(4‐cyanovaleric acid) (ACVA) were utilized to prepare temperature‐sensitive poly(N‐isopropylacrylamide) (PNIPAM) microgels by precipitation polymerization under various reaction pH conditions. Their particle sizes and swelling ratios depended on the reaction pH due to the pH dependence on the ionization degree of the decomposed fragments originating from the initiators and their hydrophilicity‐hydrophobicity. The more hydrophobic initiator, under the reaction pH conditions used, could be partitioned to a greater extent into the microgel particles due to the hydrophobicity of PNIPAM chains at the reaction temperature, which led to a more cross‐linked structure inside the microgels resulting in their smaller swelling ratio. pH dependence of surface charge density of the microgels with amidino groups or carboxylic acid groups on their surfaces was evidenced by the variation of their zeta potentials as a function of pH.     

A Microgel Construction Kit for Bioorthogonal Encapsulation and pH‐Controlled Release of Living Cells

pH‐Cleavable cell‐laden microgels with excellent long‐term viabilities were fabricated by combining bioorthogonal strain‐promoted azide–alkyne cycloaddition (SPAAC) and droplet‐based microfluidics. Poly(ethylene glycol)dicyclooctyne and dendritic poly(glycerol azide) served as bioinert hydrogel precursors. Azide conjugation was performed using different substituted acid‐labile benzacetal linkers that allowed precise control of the microgel degradation kinetics in the interesting pH range between 4.5 and 7.4. By this means, a pH‐controlled release of the encapsulated cells was achieved upon demand with no effect on cell viability and spreading. As a result, the microgel particles can be used for temporary cell encapsulation, allowing the cells to be studied and manipulated during the encapsulation and then be isolated and harvested by decomposition of the microgel scaffolds.     

新型半纤维素基磁性水凝胶的制备及性能

采用H₂O₂-Vc氧化还原体系引发半纤维素衍生物,以表面修饰的Fe₃O₄粒子作为磁性组分,利用接枝共聚方法制备了新型半纤维素基磁性水凝胶. 分别用傅里叶变换红外(FTIR)光谱、X射线光电子能谱(XPS)和扫描电子显微镜(SEM)对水凝胶的结构及形貌进行了表征,利用X射线衍射(XRD)和振动样品磁强计(VSM)对水凝胶的晶型结构及磁性能进行了分析,发现Fe₃O₄粒子均匀分散在凝胶网络中,半纤维素基磁性水凝胶表现出良好的顺磁性. 考察了丙烯酸/半纤维素比例、Fe₃O₄粒子含量及交联剂用量对水凝胶溶胀性能的影响,并探讨了该水凝胶的溶胀机理,它在pH 8 缓冲溶液中的溶胀较好符合Fickian 和Schott 动力学模型. 通过SEM和溶胀性能分析表明,随着pH值的升高水凝胶的孔径增大,水凝胶的溶胀率逐渐增大. 制备的水凝胶被用于溶菌酶吸附研究,结果表明磁性凝胶的吸附量大于非磁性水凝胶,水凝胶的吸附行为符合Freundlich 和Temkin 等温模型.     

Inducing pH responsiveness via ultralow thiol content in polyacrylamide (micro)gels with labile crosslinks

Here we present the synthesis and characterization of pH responsive polyacrylamide microgels, synthesized via free radical polymerization of acrylamide and bis (acryloylcystamine) (BAC). The gels were made with ultralow amounts of thiol functional groups incorporated into the polymer. The resulting gel monoliths were mechanically chopped into microgel particles with size distributions ranging from 80 to 200 mum. The gels exhibit an interesting reversible pH-dependent rheological behavior which led to gelling of the colloidal suspension when the pH was increased, and a low-viscosity suspension was obtained when the pH was taken back to the original value. The viscosity of the colloidal system containing MBA crosslinked microgels remained insensitive to pH. This observation motivated further analysis; viscosity measurements of the highly viscous (gel-like) state of the BAC crosslinked microgel colloidal suspension were carried out to further understand the rheological behavior of the colloidal system. Electrophoretic mobility measurements as function of pH of the BAC and MBA crosslinked colloidal polyacrylamide microgel suspensions were performed. The swelling behavior of the microgels for both colloidal systems was also determined as function of pH using static light scattering. This swelling behavior was used to rationalize the observed rheological behavior. The work presented here demonstrates that free thiol groups present within a polymer gel matrix confer pH responsive behavior to the gel in solution. The viscosity of a BAC crosslinked microgel suspension was also measured under reducing conditions. The viscosity of the microgel suspension reduced with time, due to the breakage of the disulfide bonds in the crosslinkers.