Thermal and rheological properties of hydrophobically modified responsive gels

Thermally responsive hydrogels have been prepared of N-isopropylacrylamide (NIPAAM) and a fluorinated hydrophobic comonomer, either hexafluoroisopropyl methacrylate (HFIPMA) or hexafluorobutyl methacrylate (HFBMA). Terpolymer gels containing an ionizable comonomer, methacrylic acid (MAA), were also synthesized. The swelling and mechanical properties of the gels were investigated in pure water and in aqueous NaCl solutions. All gels show thermosensitivity typical of polyNIPAAM, swelling at lower temperature and deswelling above a certain transition temperature. Hydrogels of NIPAAM and HFIPMA are homogeneous and the corresponding gel modified with methacrylic acid shows the character of a polyelectrolyte gel. However, hydrogels of NIPAAM and HFBMA are heterogeneous and the corresponding acidic gel does not behave as is typical of a polyelectrolyte gel. The acidic gel containing hexafluoroisopropyl-substituted comonomers has a high storage modulus G', showing that this gel favourably combines the properties of hydrophobically associating polymers and polyelectrolytes. Comparison of the macroscopic gels with chemically similar latex particles showed that the thermal behavior of the particles is mainly determined by the chemical composition but not by the residual surfactant adsorbed onto the polymer particles.     

Funktionalisierung des perlcopolymerisationsprodukts aus methylacrylat und 1,4-bis(vinyloxy)butan

The ester groups of copolymer beads, prepared from methyl acrylate and 1,4-bis(vinyloxy)-butane, were substituted by aminolysis with hexamethylenediamine or aminoalcohols. The resulting gel carrying amino groups was transferred into an anion exchanger by alkylation with 2-chloroethanol or into a cation exchanger by reaction with succinic anhydride. Hydrazinolysis of the starting copolymer beads resulted in gels with hydrazide groups which subsequently can be derivatized. Gels with hydroxyl groups linked to the matrix by means of spacers were obtained by reaction of the succinylated gels with 2-aminoethanol. Phosphorylation of these hydroxyl groups afforded strongly acidic cation exchangers. The yields of the derivatized products are higher and the preparations are easier than those of the known methods. The 11 gel derivatives synthesized from the starting gel are mechanically stable, resistent to hydrolysis in the pH range between 1 and 14, chemically stable at temperatures up to 130°C and obtainable with a variety of pore sizes. The derivatized, cross-linked polymer beads, applicable in aqueous systems as well as in organic solvents, should find application in chromatography, in solid-phase synthesis and as basic gels in biotechnical processes.     

Thermoresponsive comb-shaped copolymer-Si(100) hybrids for accelerated temperature-dependent cell detachment

Well-defined comb-shaped copolymer-Si(100) hybrids were prepared, via successive surface-initiated atom transfer radical polymerizations (ATRPs) of glycidyl methacrylate (GMA) and N-isopropylacrylamide (NIPAAm), for accelerated cell detachment at a lower temperature. The Si-C bonded comb copolymer consisted of a well-defined (nearly monodispersed) poly(glycidyl methacrylate) (P(GMA)) main chain, a well-defined NIPAAm polymer (P(NIPAAm) block, and well-defined P(NIPAAm) side chains. The ring opening reaction of epoxy groups of the P(GMA) main chain with 2-chloropropionic acid resulted in the immobilization of the alpha-chloroester groups (the ATRP initiators for the NIPAAm side chains) and the concomitant formation of hydroxyl groups. P(NIPAAm) acted as the thermoresponsive side chains of the comb copolymer for control of cell adhesion and detachment, while the P(GMA) main chain with hydroxyl groups provided a local hydrophilic microenvironment. The unique microstructure of the comb copolymer brushes facilitated cell recovery at 20 degrees C (below the lower critical solution temperature (LCST) of P(NIPAAm)) without restraining cell attachments and growth at 37 degrees C. The accelerated detachment of cells indicated that the underlying hydrophilic environment of the comb copolymer brushes contributed to speedy hydration of the P(NIPAAm) segments below the LCST. The thermoresponsive comb copolymer-Si(100) hybrids are potentially useful as adhesion modifiers for cells in silicon-based biomedical devices.     

Synthesis and characterization of degradable bioconjugated hydrogels with hyperbranched multifunctional cross-linkers

Hyperbranched poly(ester amide) polymer (Hybrane? S1200, M_n 1200 g mol^?1) was functionalized with maleic anhydride (MA) and propylene sulfide, to obtain multifunctional cross-linkers with fumaric and thiol end groups, S1200MA and S1200SH, respectively. The degree of substitution (DS) of maleic acid groups was controlled by varying the molar ratio of MA to S1200 in the reaction mixture. Hydrogels were obtained by UV cross-linking of functionalized S1200 and poly(ethylene glycol) diacrylate in aqueous solutions. Compressive modulus increased with decreasing S1200/PEG ratio and also depended on the DS of the multifunctional cross-linker (S1200). Also, heparin-based macromonomers together with functionalized hyperbranched polymers were used to construct novel functional hydrogels. The multivalent hyperbranched polymers allowed high cross-linking densities in heparin modified gels while introducing biodegradation sites. Both heparin presence and acrylate/thiol ratio had an impact on degradation profiles and morphologies. Hyperbranched cross-linked hydrogels showed no evidence of cell toxicity. Overall, the multifunctional cross-linkers afford hydrogels with promising properties that suggest that these may be suitable for tissue engineering applications.     

Free‐radical crosslinking polymerization of unsymmetrical divinyl compounds, 1 Gelation in the polymerization of allyl methacrylate

As an extension of our continuing studies concerned with the free‐radical crosslinking polymerization of multivinyl compounds, this article deals with the gelation in the polymerization of allyl methacrylate (AMA) as a typical unsymmetrical divinyl compound containing two types of vinyl groups such as methacryloyl and allyl ones having quite different reactivities. Thus, AMA was polymerized in bulk or in a 1,4‐dioxane solution using an azo‐initiator at 50°C in the presence of lauryl mercaptan as chain transfer agent. The actual gel point was compared with the calculated one according to Gordon's equation by tentatively supposing equal reactivity of both vinyl groups. Tailed molecular‐weight distribution curves were observed. The swelling ratios of the resulting gels obtained just beyond the gel point was very high. Thus, the intermolecular crosslinking occurred predominantly in the bulk polymerization. Even in the solution polymerization, the occurrence of intramolecular crosslinking was only a little. This was supported by the r.m.s. radii of gyration and second virial coefficients of resulting prepolymers.     

Water-soluble photoresins based on azosulfonates

Water-soluble polymers with pendant azosulfonate groups were synthesized by radical copolymerization of 3-vinylphenylazosulfonate with methyl methacrylate or styrene. The copolymerization parameters were determined for these systems. Furthermore, photoactive polymers were obtained by reaction of poly[(methacryloyl chloride)-co-(methyl methacrylate)] with azosulfonates containing phenolic or amino groups. Due to their solubility in water and their photocrosslinking behaviour, these polymers are attractive candidates for photoprinting and photoresist materials.     

Oscillating Swelling–Shrinking Dynamics and Diffusive Properties of Weakly Cationic Poly(Aminoalkyl Methacrylate)‐Based Cryogels: Quantifying the Influence of Polymer Network Parameters

Thermodynamic properties of swelling equilibria and variability of dynamic response of pH‐sensitive polybases are examined. Poly(aminoalkyl methacrylate)‐based cryogels and hydrogels are prepared in a facile way by crosslinking polymerization of amine functional monomer N,N‐dimethylaminoethyl methacrylate (DMAEMA) in the presence of diethyleneglycol dimethacrylate as crosslinker at temperatures below and above freezing point of polymerization solvent, water, via cryogelation and conventional crosslinking polymerization. The effect of polymerization temperature on swelling characteristics of the prepared polybasic gels is investigated as a function of the gel‐preparation concentration. The overshooting effect is observed during pH‐dependent swelling of poly(N,N‐dimethylaminoethyl methacrylate) (PDMAEMA) hydrogels in acidic medium. Protonation/deprotonation of tertiary amine groups in network‐forming polymer demonstrates critical swelling behavior as pH of the swelling medium increases. Oscillating swelling–shrinking studies are performed and effective diffusion coefficient of water within PDMAEMA cryogel and hydrogel matrices is estimated using the dynamic swelling profiles. The mechanism of cyclic swelling–shrinking process of PDMAEMA cryogels and hydrogels are analyzed to control their pulsatile output patterns in metabolic oscillations. Considering the swelling process occurs through Fickian diffusion mechanism in acidic solutions, polybasic cryogels and hydrogels prepared in this study are thus proposed as good candidates for delivery applications.     

Photoreactive diimide models of benzhydroltetracarboxylic dianhydride: Synthesis,characterization and photopolymerization

The synthesis, characterization and photopolymerization of bisimide compounds carrying a photoreactive methacryloyl group were investigated. Those photoreactive diimide models, derived from benzhydroltetracarboxylic dianhydride ( 1 ), were prepared in N-methyl-2-pyrrolinone (NMP), either by a thermal or by a chemical imidization. In the thermal method, the bisimide carrying benzhydrol group was first synthesized by condensation of 1 with 4-tert-butylaniline at 180°C. The hydroxyl group was then chemically modified by an excess of methacryloyl isocyanate ( 6 ) in NMP. In the chemical method, a photosensitive dianhydride, derived from the reaction between 1 and 6 , was prepared and then condensed with aniline at 25°C by means of propionic anhydride with triethylamine, which leads to the formation of the corresponding imide. By means of IR, the photopolymerization of the methacrylic double bond that takes place in the presence of a photoinitiator under irradiation at 365 nm was then investigated. It was found that the most effective photoinitiator for these photoreactive model compounds is the Michler's ketone/triethanolamine system. The further aim of the present investigation is to prepare novel negative-type photosensitive polyimides.     

Soft contact lenses functionalized with pendant cyclodextrins for controlled drug delivery

The aim of this work was to develop acrylic hydrogels with high proportions of cyclodextrins maintaining the mechanical properties and the biocompatibility of the starting hydrogels, but notably improving their ability to load drugs and to control their release rate. Poly(hydroxyethylmethacrylate) hydrogels were prepared by copolymerization with glycidyl methacrylate (GMA) at various proportions and then β-cyclodextrin (βCD) was grafted to the network by reaction with the glycidyl groups under mild conditions. This led to networks in which the βCDs form no part of the structural chains but they are hanging on 2–3 ether bonds through the hydroxyl groups. The pendant βCDs did not modify the light transmittance, glass transition temperature, swelling degree, viscoelasticity, oxygen permeability, or surface contact angle of the hydrogels, but decreased their friction coefficient by 50% and improved diclofenac loading by 1300% and enhanced drug affinity 15-fold. The hydrogels were able to prevent drug leakage to a common conservation liquid for soft contact lenses (SCLs) and to sustain drug delivery in lacrimal fluid for two weeks. To summarize, the hydrogels with pendant βCDs are particularly useful for the development of cytocompatible medicated implants or biomedical devices, such as drug-loaded SCLs.     

Synthesis of polymers with pendant spiro orthoester groups

This paper describes the synthesis of polymers having spiro orthoester side groups, starting from lactones with methacrylate side groups. The spiro orthoester polymers are synthesized by a reaction with an oxirane. The hydroxy-functional lactones 3-hydroxy-4,4-dimethyl-2-oxotetrahydrofuran ( 1 ) and 5-hydroxymethyl-2-oxotetrahydrofuran ( 13 ) were esterificated with methacryloyl chloride. The esterification of 5-oxotetrahydrofuran-2-carboxylic acid ( 6 ) and 2,2-dimethyl-5-oxotetrahydrofuran-3-carboxylic acid ( 11 ) with 2-hydroxyethyl acrylate and 2-hydroxyethyl methacrylate yielded the functionalized precursors for the synthesis of polymeric spiro orthoesters. These monomers were polymerized and copolymerized with methyl methacrylate and characterized. Furtheron, the obtained polymers with lactone groups were converted to the corresponding spiro orthoesters using 2,3-epoxypropyl phenyl ether in the presence of boron trifluoride.     

Swelling behavior of hydrogels containing phosphate groups

Hydrogels containing phosphate groups were prepared by copolymerization of 2-methacryloyl-oxyethyl dihydrogen phosphate (phosmer) and various hydrophilic monomers [N,N-dimethyl-acrylamide (DMAAm), acrylic acid (AAc) and 2-hydroxyethyl methacrylate (HEMA)], and the swelling behavior was investigated. These hydrogels are thermo-sensitive. Phosmer-DMAAm and phosmer-HEMA hydrogel deswell with increasing temperature, but for the phosmer-AAc hydrogel the swelling ratio increases with temperature. Interestingly, the swelling ratio decreases with an increase in phosphate group content. This unusual behavior may arise from the phosphate group acting both as the functional group and the crosslinking agent.     

A comparative biocompatibility study of microspheres based on crosslinked dextran or poly(lactic-co-glycolic)acid after subcutaneous injection in rats

Microspheres based on methacrylated dextran (dex-MA), dextran derivatized with lactate-hydroxyethyl methacrylate (dex-lactate-HEMA) or derivatized with HEMA (dex-HEMA) were prepared. The microspheres were injected subcutaneously in rats and the effect of the particle size and network characteristics [initial water content and degree of methacrylate substitution (DS)] on the tissue reaction was investigated for 6 weeks. As a control, poly(lactic-co-glycolic)acid (PLGA) microspheres with varying sizes (unsized, smaller than 10 microm, smaller and larger than 20 microm) were injected as well. A mild tissue reaction to the PLGA microspheres was observed, characterized by infiltration of macrophages (M?s) and some granulocytes. Six weeks postinjection, the PLGA microspheres were still present. However, their size was decreased indicating degradation and many spheres had been phagocytosed. The tissue reaction was hardly affected by size differences, except for particles smaller than 10 microm, which induced an extensive tissue reaction. The initial tissue reaction to nondegradable dex-MA microspheres was stronger than towards the PLGA microspheres, but at day 10 the tissue reactions were comparable for both groups. Six weeks postinjection, the dex-MA microspheres were completely phagocytosed, and no signs of degradation were observed. The size and initial water content of dex-MA microspheres hardly affected the tissue response, although less granulocytes were observed for microspheres with higher DS. Slowly degrading dextran microspheres composed of dex-(lactate(1)-)HEMA induced a tissue reaction comparable to the PLGA microspheres. However, degradation of the dex-(lactate(1,3)-)HEMA microspheres was associated with an increased number of M?'s and giant cells, both phagocytosing the microspheres and their degradation products. Similar to PLGA, no adverse reactions were observed for the nondegradable dex-MA and degradable dextran microspheres. This study shows that both nondegradable and degradable dextran-based microspheres are well tolerated after subcutaneous injection in rats, which make them interesting candidates as controlled drug delivery systems.     

In vivo biocompatibility of dextran-based hydrogels

Dextran-based hydrogels were obtained by polymerization of aqueous solutions of methacrylated dextran (dex-MA) or lactate-hydroxyethyl methacrylate-derivatized dextran (dex-lactate-HEMA). Both nondegradable dex-MA and degradable dex-lactate-HEMA disk-shaped hydrogels, varying in initial water content and degree of substitution (DS, the number of methacrylate groups per 100 glucose units), were implanted subcutaneously in rats. The tissue reaction was evaluated over a period of 6 weeks. The initial foreign-body reaction to the dex-MA hydrogels was characterized by infiltration of granulocytes and macrophages and the formation of fibrin, and exudate, as well as new blood vessels. This reaction depended on the initial water content as well as on the DS of the hydrogel and decreased within 10 days. The mildest tissue response was observed for the gel with the highest water content and intermediate DS. At day 21 all dex-MA hydrogels were surrounded by a fibrous capsule and no toxic effects on the surrounding tissue were found. No signs of degradation were observed. The initial foreign-body reaction to the degradable dex-lactate-HEMA hydrogels was less severe compared with the dex-MA gels. In general, the size of the dex-lactate-HEMA hydrogels increased progressively with time and finally the gels completely dissolved. Degradation of the dex-lactate-HEMA hydrogels was associated with infiltration of macrophages and the formation of giant cells, both of which phagocytosed pieces of the hydrogel. A good correlation between the in vitro and the in vivo degradation time was found. This suggests that extra-cellular degradation is not caused by enzymes but depends only on hydrolysis of the ester and/or carbonate bonds present in the crosslinks of the hydrogels. After 21 days, the degradable hydrogels, as such, could not be retrieved, but accumulation of macrophages and giant cells was observed, both of which contained particles of the gels intracellularly. As for the dex-MA hydrogels, no toxic effects on the surrounding tissue were found. The results presented in this study demonstrate that dextran-based hydrogels can be considered as biocompatible materials, making these hydrogels attractive systems for drug delivery purposes.     

Stereoregularity of poly(methacryloyl chloride) and poly(methacrylic salts) prepared by photopolymerization

Poly(methacryloyl chloride) (PMACl) and poly(methacrylic tetramethylammonium salts) and poly(methacrylic tetraethyl ammonium salts) (PMAAN⁺) have been prepared by radical photopolymerization at different temperatures. The obtained molecular weights are independent of the polymerization temperature in the range studied (+24 to ?30°C) which is in agreement with a purely photochemical process. The dependence of the tacticity upon temperature was examined by means of NMR spectroscopy. Deviations from Bernoullian statistics were confirmed. PMAAN⁺ salts prepared in water are highly syndiotactic and a nearly pure syndiotactic structure is obtained at +5°C. This behavior is explained by the repulsive interactions between the carboxylate anions promoting the racemic placement. The tacticity of PMACl is comparable with that of poly(methacryloyl fluoride). The structure is less syndiotactic and much more isotactic than that of poly(methyl methacrylate). This result is interpreted by considering the electron-withdrawing character of chlorine and fluorine atoms which affects the electronic structure and polarity of the carbonyl group near to the macroradical and competes with the preferential syndiotactic placement observed with α-substituted acrylates.     

Preparation and volume change of polyimide gels

A soluble fluorine-containing polyimide derived from 4,4′-(hexafluoroisopropylidene)diphthalic anhydride (6FDA) and 3,3′-dihydroxy-4,4′-diaminobiphenyl (DHBP) was prepared and successfully crosslinked via the reaction between hexamethylene diisocyanate (HMDI) and the hydroxyl groups on the phenylene rings, leading to the formation of a soft polyimide gel. The gelation times vary according to the amount of crosslinker. Higher concentration of the crosslinker and catalyst accelerates the gelation reaction. We found that the crosslinker, HMDI, not only reacts with hydroxyl groups on the phenylene rings but also forms an oligomeric chain through the reaction with moisture. The conversion of the crosslinker was estimated from NMR. The volume changes of the gels against solvent composition were also studied. The polyimide gels swell when the N-methyl-2-pyrrolidone (NMP) weight fraction is larger than 0.80 in the mixed solvent NMP/water at 20°C. During the swelling process less time is needed for the gels to reach the equilibrium in NMP richer solvents. This is the first report as far as we know on the synthesis of a polyimide gel and the study of its properties.     

Improved cell adhesion and proliferation on synthetic phosphonic acid-containing hydrogels

Hydrogels with tissue-like mechanical properties are highly attractive scaffolds for tissue engineering. In this study, copolymers containing vinyl phosphonic acid (VPA) and acrylamide (AM) were tested for their swelling, protein uptake in serum supplemented medium, and cell adhesion and proliferation. The swelling of the gels in serum containing culture medium increased with increasing VPA content. The presence of VPA also increased protein uptake of gels in medium; gels polymerized with more than 50% of VPA absorbed as much as 100 microg/cm(2) of protein, twice the amount absorbed by gels made with only acrylamide. The adhesion and growth of the three types of cells, NIH 3T3 fibroblast, osteoblast-like MG-63 and Saos-2, were significantly improved on the gels made with 50% or more VPA; the number of adherent Mg-63 cells increased three-fold while the growth rate increased four-fold. Similar results were obtained for Saos-2 and 3T3 cells. The adhesion and growth of the three cell types on gels with sufficient phosphonate content were at least comparable to, or even better than, that on commercially available tissue culture plates. These results suggest great potential of anionic gels in bone tissue engineering.     

Swelling and Mechanical Properties of a Temperature‐Sensitive Dextran Hydrogel and its Bioseparation Applications

Summary: A series of temperature‐sensitive dextran hydrogels (poly(NIPA‐co‐GMA‐Dex)) were synthesized by the copolymerization of glycidyl methacrylate‐derivatized dextran (GMA‐Dex) and N‐isopropylacrylamide (NIPA) in aqueous solution. Their swelling and mechanical properties and bioseparation behaviors were studied. It is found that poly(NIPA‐co‐GMA‐Dex) hydrogels simultaneously exhibit much better swelling and mechanical properties. The interactions between poly(NIPA‐co‐GMA‐Dex) hydrogels and sodium dodecylsulfate (SDS), Rutin, and DL ‐α‐alanine were different because of their different hydrophobic nature, polarity, and molecular structure, and obviously depend on the temperature: the mechanism is discussed. In addition, using poly(NIPA‐co‐GMA‐Dex) hydrogels as the absorbents, gel‐extraction separation experiments of dextran and BSA solutions showed that the separation ability of poly(NIPA‐co‐GMA‐Dex) hydrogels obviously increased upon reaching the LCST.

Temperature dependence of the swelling ratio of the PNIPA (▪) and poly(NIPA‐co‐GMA‐Dex) hydrogels (r = 0.2(•), 0.4 (▴), 0.5 (▾), 0.6(♦), 0.8 (+)).     

Simple Photochemical Route to Block Copolymers via Two‐Step Sequential Type II Photoinitiation

A simple method for the preparation of block copolymers by a two‐step sequential Type II photoinitiation is described. In the first step, amine functionalized poly(methyl methacrylate) (PMMA‐N(Et)₂) is prepared by photopolymerization of methyl methacrylate at λ = 350 nm using benzophenone and triethyl amine as photosensitizer and hydrogen donor, respectively. Subsequent benzophenone‐sensitized photopolymerization of tert‐butyl acrylate using PMMA‐N(Et)₂ as hydrogen donor yielded poly(methyl methacrylate)‐block‐poly(tert‐butyl acrylate). The obtained hydrophobic block copolymer is readily converted to amphiphilic polymer by hydrolysis of the tert‐butyl ester moieties of the block copolymer as demonstrated by contact angle measurements. All polymers are characterized by NMR, Fourier transform infrared and UV–vis spectroscopies, and differential scanning calorimetry (DSC) thermal analyses.     

Enzyme-mediated fast in situ formation of hydrogels from dextran-tyramine conjugates

Dextran hydrogels were formed in situ by enzymatic crosslinking of dextran-tyramine conjugates and their mechanical, swelling and degradation properties were evaluated. Two types of dextran-tyramine conjugates (M(n,dextran)=14k, M(w)/M(n)=1.45), i.e. dextran-tyramine linked by a urethane bond (denoted as Dex-TA) or by an ester-containing diglycolic group (denoted as Dex-DG-TA), with different degrees of substitution (DS) were prepared. Hydrogels were rapidly formed under physiological conditions from Dex-TA DS 10 or 15 and Dex-DG-TA DS 10 at or above a concentration of 2.5 wt% in the presence of H(2)O(2) and horseradish peroxidase (HRP). The gelation time ranged from 5s to 9 min depending on the polymer concentration and HRP/TA and H(2)O(2)/TA ratios. Rheological analysis showed that these hydrogels are highly elastic. The storage modulus (G'), which varied from 3 to 41 kPa, increased with increasing polymer concentration, increasing HRP/TA ratio and decreasing H(2)O(2)/TA ratio. The swelling/degradation studies showed that under physiological conditions, Dex-TA hydrogels are rather stable with less than 25% loss of gel weight in 5 months, whereas Dex-DG-TA hydrogels are completely degraded within 4-10d. These results demonstrate that enzymatic crosslinking is an efficient way to obtain fast in situ formation of hydrogels. These dextran-based hydrogels are promising for use as injectable systems for biomedical applications including tissue engineering and protein delivery.     

Nanostructured hybrid hydrogels prepared by a combination of atom transfer radical polymerization and free radical polymerization

A new method to prepare nanostructured hybrid hydrogels by incorporating well-defined poly(oligo (ethylene oxide) monomethyl ether methacrylate) (POEO₃₀₀MA) nanogels of sizes 110–120 nm into a larger three-dimensional (3D) matrix was developed for drug delivery scaffolds for tissue engineering applications. Rhodamine B isothiocyanate-labeled dextran (RITC-Dx) or fluorescein isothiocyanate-labeled dextran (FITC-Dx)-loaded POEO₃₀₀MA nanogels with pendant hydroxyl groups were prepared by activators generated electron transfer atom transfer radical polymerization (AGET ATRP) in cyclohexane inverse miniemulsion. Hydroxyl-containing nanogels were functionalized with methacrylated groups to generate photoreactive nanospheres.¹H NMR spectroscopy confirmed that polymerizable nanogels were successfully incorporated covalently into 3D hyaluronic acid-glycidyl methacrylate (HAGM) hydrogels after free radical photopolymerization (FRP). The introduction of disulfide moieties into the polymerizable groups resulted in a controlled release of nanogels from cross-linked HAGM hydrogels under a reducing environment. The effect of gel hybridization on the macroscopic properties (swelling and mechanics) was studied. It is shown that swelling and nanogel content are independent of scaffold mechanics. In-vitro assays showed the nanostructured hybrid hydrogels were cytocompatible and the GRGDS (Gly–Arg–Gly–Asp–Ser) contained in the nanogel structure promoted cell–substrate interactions within 4 days of incubation. These nanostructured hydrogels have potential as an artificial extracellular matrix (ECM) impermeable to low molecular weight biomolecules and with controlled pharmaceutical release capability. Moreover, the nanogels can control drug or biomolecule delivery, while hyaluronic acid based-hydrogels can act as a macroscopic scaffold for tissue regeneration and regulator for nanogel release.