Synthesis and characterization of biodegradable hydrophobic–hydrophilic hydrogel networks with a controlled swelling property

A biodegradable polymer network hydrogel system with both hydrophilic and hydrophobic components was synthesized and characterized. The hydrophilic and hydrophobic components were dextran and poly(D,L )lactic acid (PDLLA), respectively. These two polymers were chemically modified for incorporating unsaturated groups for subsequent UV crosslinking to generate a hydrogel with a three‐dimensional network structure. The effects of the reaction conditions on the synthesis of a dextran derivative of allyl isocyanate (dex‐AI) were studied. All newly synthesized materials were characterized by Fourier transform infrared and NMR. The swelling property of the hydrogels was studied in buffer solutions of different pHs. The results of this study showed that a wide‐range swelling property was obtained by changes in the dex‐AI/PDLLA composition ratio, the type and degree of unsaturated groups incorporated into dextran, and the UV photocrosslinking time. The solvent extraction effect on the swelling property of the hydrogels was also studied. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 2392–2404, 2000     

Microphase‐separated structure of telechelic urethane acrylate anionomers and their network in various solvents

Telechelic urethane acrylate anionomer (UAA) chain showed less viscosity and polyelectrolyte behavior in water than dimethyl acetamide (DMAc) because of hydrophobic aggregation. UAA networks prepared in different solvents (water and DMAc) exhibited very different swelling behaviors in the same swelling medium, which can be interpreted as due to the very different microstructures formed in the solvents. UAA networks prepared with water (UAHG networks) had microphase‐separated hydrophilic and hydrophobic domains, whereas UAA networks synthesized with DMAc (UADG networks) had relatively homogeneous network structures. The mechanical property of the UAHG and UADG networks, measured with a dynamic mechanical analyzer, was also very sensitive to the solvent type used during the crosslinking reaction. UAHG networks with a microphase‐separated structure had a higher modulus than UADG networks. The results of the mechanical property measurements showed that water was a much better solvent for the hydrophilic hard segments of UAA chain than DMAc, even though DMAc dissolved both hydrophilic and hydrophobic segments of UAA chain. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 2081–2095, 2000     

Effect of hydrophilicity on the properties of a degradable polylactide

A series of polylactide networks has been prepared by the copolymerization of a biodegradable oligolactide macromer with hydrophobic methyl methacrylate monomer and hydrophilic hydroxyethyl acrylate monomer, with different amounts of the hydrophilic monomer. The incorporation of the hydrophilic units into the network has been characterized with thermogravimetric analysis, differential scanning calorimetry, and dynamic mechanical spectrometry. A homogeneous material results, showing a single glass‐transition temperature and a characteristic relaxation behavior that is not the sum of those of the pure components separately. Additional hydrophilic units in the network chains lower the rubbery modulus, keeping a high modulus value at room temperature, and manifestly increase the degradation rate of the polymer. This can be attributed both to the higher water swellability of the network when hydrophilic units are present and to the higher water diffusion coefficient in a network, which has a lower crosslinking density. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 656–664, 2006     

Synthesis and characterization of novel thermoresponsive‐co‐biodegradable hydrogels composed of N‐isopropylacrylamide,poly(L‐lactic acid), and dextran

A series of novel multifunctional hydrogels that combined the merits of both thermoresponsive and biodegradable polymeric materials were designed, synthesized, and characterized. The hydrogels were copolymeric networks composed of N‐isopropylacrylamide (NIPAAM) as a thermoresponsive component, poly(L‐lactic acid) (PLLA) as a hydrolytically degradable and hydrophobic component, and dextran as an enzymatically degradable and hydrophilic component. The chemical structures of the hydrogels were characterized by an attenuated total reflection–Fourier transform infrared spectroscopy (ATR–FTIR) technique. The hydrogels were thermoresponsive, showing a lower critical solution temperature (LCST) at approximately 32 °C, and their swelling properties strongly depended on temperature changes, the balance of the hydrophilic/hydrophobic components, and the degradation of the PLLA component. The degradation of the hydrogels caused by hydrolytic cleavage of ester bonds in the PLLA component was faster at 25 °C below the LCST than at 37 °C above the LCST, determined by the ATR–FTIR technique. Due to their multifunctional properties, the designed hydrogels show great potential for biomedical applications, including drug delivery and tissue engineering. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5054–5066, 2004     

Amphiphilic urethane acrylate hydrogels having heterophasic gel structure: swelling behaviors and mechanical properties

 Amphiphilic urethane acrylate hydrogels containing ionic group (dimethylopropionic acid, DMPA) were prepared by varying the molecular weight of the soft segment (polyether type, PTMG) and type of diisocyanate, and their swelling behaviors and mechanical properties were examined. They showed amphiphilic property due to the hydrophilic ionic groups and hydrophobic polyethers comprising the urethane acrylate network. Heterophasic gel structure could be found for the hydrogels prepared in water, but not for the hydrogels in organic solvent (1,4-dioxane), through scanning electron microscopy. Because of this heterophasic gel structure, they were able to take in a large amount of water as well. The hydrophobic interaction generated by the polyether soft segments between urethane acrylate network chains decreased the degree of swelling, however, increased reversibly the tensile strengths at equilibrium swelling state. MDI-based hydrogel showed low swelling ratio and high tensile strength because of its ordered hard domain structure. These amphiphilic urethane acrylate hydrogels showed salt- and pH-dependent swelling behaviors. Received: 26 September 1997 Accepted: 24 December 1997     

Mechanically tough and recoverable hydrogels via dual physical crosslinkings

Development of functional tough hydrogels with new network structures and energy dissipation mechanisms has great promise for many applications. Here, a new type of physical hydrogel crosslinked by hydrophobic association and hydrogen bonds was synthesized by a facile micellar copolymerization of hydrophobic methyl acrylate (MA) monomers and hydrophilic N-hydroxyethyl acrylamide (HEAA) monomers in the presence of Tween80 micelles. Strong hydrophobic association between inner MA and Tween80 and hydrogen bonds between external polyHEAA and Tween80 provide two distinct crosslinkers to construct mechanically tough and recoverable network. Mechanical properties of polyHEAA-MA@Tween80 hydrogels strongly depended on network components (HEAA, MA; Tween80 concentrations). At optimal conditions, the hydrogels can achieve fracture stress of 700 kPa, fracture strain of 1687 mm/mm, elastic modulus of 195 kPa, and tearing energy of 1598 J/m². Due to the reversible nature of physical interactions, polyHEAA-MA@Tween80 hydrogels can achieve fast stiffness/toughness recovery of 60%/33% without any external stimuli and resting time at room temperature. This work demonstrates a new design strategy to fabricate a new a single-network hydrogel with high mechanical and self-recovery properties by incorporating both hydrophobic association and hydrogen bonds in the network, which may provide alternative viewpoint for the design of multifunctional tough hydrogels. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018 , 56, 1294–1305     

Dual cross-linked networks hydrogels with unique swelling behavior and high mechanical strength: based on silica nanoparticle and hydrophobic association

A series of physically cross-linked hydrogels composed poly(acrylic acid) and octylphenol polyoxyethylene acrylate with high mechanical strength are reported here with dual cross-linked networks that formed by silica nanoparticles (SNs) and hydrophobic association micro-domains (HAMDs). Acrylic acid (AA) and octylphenol polyoxyethylene acrylate with 10 ethoxyl units (OP-10-AC) as basic monomers in situ graft from the SNs surface to build poly(acrylic acid) hydrophilic backbone chains with randomly distributed OP-10-AC hydrophobic side chains. The entanglements among grafted backbone polymer chains and hydrophobic branch architecture lead to the SNs and HAMDs play the role of physical cross-links for the hydrogels network structure. The rheological behavior and polymer concentration for gelation process are measured to examine the critical gelation conditions. The correlation of the polymer dual cross-linked networks with hydrogels swelling behavior, gel-to-sol phase transition, and mechanical strength are addressed, and the results imply that the unique dual cross-linking networks contribute the hydrogels distinctive swelling behavior and excellent tensile strength. The effects of SNs content, molecular weight of polymer backbone, and temperature on hydrogels properties are studied, and the results indicate that the physical hydrogel network integrity is depended on the SNs and HAMDs concentration.     

Characterization of the network properties of poly(ethylene glycol)–acrylate hydrogels prepared by variations in the ethanol–water solvent composition during crosslinking copolymerization

The characteristics of poly(ethylene glycol) (PEG)–acrylate hydrogel networks were investigated as a function of the ethanol–water solvent composition during free‐radical crosslinking copolymerization. Macromonomer (88% ω‐methoxy‐PEG–acrylate and 10% ω‐phenoxy‐PEG–acrylate) and crosslinker (2% PEG–diacrylate) concentrations were kept constant. As the copolymerization progressed, the polymer solution in 100% ethanol became increasingly turbid, indicating the development of a heterogeneous network structure. In 100% water, however, the initially turbid polymer solution became increasingly transparent as the crosslinking copolymerization progressed. All the gels were optically clear upon equilibration in water. Kinetic studies, with attenuated total reflectance‐infrared, showed a long induction period, along with a lowered reaction rate, in 100% ethanol, and a decrease in conversion with an increase in ethanol content. These results agree with the UV analysis of the sol fractions, which indicated an increase in the amounts of unreacted PEG–acrylates with an increase in the ethanol content. The gels which were formed with a high ethanol concentration exhibited lower Young's modulus and higher swelling ability, suggesting that the network structure was significantly affected by the solvent composition during free‐radical crosslinking copolymerization. From the stress–strain and swelling experiments, the Flory–Huggins interaction parameter was evaluated. The creep characteristics of the hydrogels were modeled with two Kelvin elements. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 2677–2684, 2002     

Versatile functionalization of polyester hydrogels with electroactive aniline oligomers

Functionalizing aliphatic polyester hydrogels with an aniline oligomer is a means of achieving electrically conductive and degradable hydrogels. To lower the aniline oligomer content while maintaining a high conductivity and to overcome the acidic degradation product from polylactide reported in our previous work, a series of electroactive and degradable hydrogels based on polycaprolactone (PCL) hydrogels and carboxyl‐capped aniline pentamer (CCAP) were synthesized by a simple coupling reaction at room temperature. The reaction was carried out between the hydroxyl groups of hydroxyethylmethacrylate in a photopolymerized glycidyl methacrylate (GMA)‐functionalized PCL‐poly(ethylene glycol)‐PCL degradable network and carboxyl group of CCAP, using 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide as water‐condensing agent and 4‐dimethylaminopyridine as catalyst. The electroactivity of the hydrogels was verified by cyclic voltammetry, which showed three pairs of redox peaks. The electrical conductivities and swelling ratios of these hydrogels were controlled by the CCAP content, the poly(ethylene glycol) molecular weight in the macromer, and the crosslinking density of the hydrogels. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Synthesis and burst strength of water‐swollen immunoisolatory tubules

A series of amphiphilic hydrogel tubules have been prepared by copolymerizing/crosslinking hydrophilic poly(dimethylacrylamide) segments with hydrophobic di‐, tri‐, and octamethacrylate‐telechelic polyisobutylene crosslinkers, and their elastic modulus and burst strength in the water‐swollen state were investigated. Because the burst characteristics of hydrogels have not yet been quantitatively investigated, equipment was designed and built to generate fundamental insight into the burst properties of thin‐walled (200–250 μm) narrow lumen (2–3 mm i.d.) water‐swollen tubules. The theory developed to describe quantitatively the inflation behavior of thin‐walled rubber tubules was adapted to treat our experimental observations. Changes in the burst strength, elastic modulus, and expansion during the inflation of hydrogel tubules were interpreted in terms of the molecular weight of the hydrophilic segments between crosslinking sites (M_{c,hydrophilic}), which in turn was calculated according to the rubber elasticity theory. According to these investigations, the burst strength of our water‐swollen amphiphilic tubules is in the 0.2–0.5 MPa range, which is sufficient for implantation and immunoisolatory applications. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2075–2084, 2002     

Enzymatic bioactivity investigation of glucose oxidase modified with hydrophilic or hydrophobic polymers via in situ RAFT polymerization

Biomacromolecules, such as enzymes are widely used for biocatalysis, both at academic and industrial level, due to their high specificity and wide applications in different reaction media. Herein, taking GOx as a representative enzyme, in‐situ RAFT polymerization of four different monomers including acrylic acid (AA), methyl acrylate (MA), poly (ethylene glycol) acrylate (PEG‐A) and tert‐butyl acrylate (TBA) were polymerized directly on the surface of GOx to afford GOx‐poly (PEG‐A)(GOx‐PPEG‐A), GOx‐poly(MA)(GOx‐PMA), GOx‐poly(AA)(GOx‐PAA), and GOx‐poly(TBA)(GOx‐PTBA) conjugates, respectively. Thereinto, PAA and PPEG‐A represent the hydrophilic polymers, while PMA and PTBA stand for the hydrophobic ones. Effects of different polymer on the properties of GOx were investigated by measuring the bioactivity and stability of the as‐prepared and different GOx‐polymer conjugates. Higher bioactivity was obtained for GOx modified with hydrophilic polymers compared with that modified with hydrophobic ones. All the tested polymers can enhance the stability of the GOx, while the hydrophobic GOx‐polymers conjugates exhibited much better stability than the hydrophilic ones. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 1289–1293     

Hydrophobic and hydrophilic aggregation of tailor‐made urethane acrylate anionomers in various solvents and their network structures

Tailor‐made urethane acrylate anionomer (UAA) chains show higher viscosity and polyelectrolyte behavior in dimethyl sulfoxide (DMSO) than in water and toluene. Water is a nonsolvent for the hydrophobic soft segment but a good solvent for the hydrophilic hard segments, so hydrophobic segments are aggregated and form particles in the water phase, resulting in a smaller viscosity. Also, the fact that the viscosity of UAA chains is lowest in toluene can be interpreted as a result of ionic aggregation due to the nonpolarity of toluene. The structures of UAA networks dramatically change with the nature of the solvents used (i.e., the interaction between the UAA chains and the solvents used changes); this is confirmed by the results of tensile property, morphology, and wide‐angle X‐ray scattering data. Ionic aggregation formed in UAA/toluene (UATG networks) and hydrophobic aggregation formed in UAA/water (UAAG networks) are locked in by a chemical crosslinking reaction and result in a greater modulus and X‐ray scattering intensity. The greater elongation and swelling ratio in methylene chloride of UATG networks prepared in a UAA/toluene solution indicates that toluene is a better solvent than DMSO for the hydrophobic segments of UAA chains. Also, the greater swelling ratio in a pH 11 buffer solution and greater modulus of UAAG networks show that water is a better solvent than DMSO for hydrophilic ionic segments. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 1903–1916, 2000     

The effect of methyl group on the mechanical properties of hydrophobic association hydrogel

Hydrophobic association hydrogels were fabricated via micellar copolymerization of acrylamide and hydrophobic monomers lauryl (meth)acrylate (LA or LMA) in an aqueous solution of sodium dodecyl sulfate. The effect of methyl groups of hydrophobic monomers on the crosslinking network structure and mechanical behavior of the gels was investigated on the basis of rubber elastic theory. It was found that the LMA-gel exhibited higher effective crosslink density and elastic modulus. The methyl groups of hydrophobic monomers limited the flexibility of the methacrylate backbone in the association domain, which resulted in the increment of chains constraints. With the increase of stretch rate, the dissipated energy of LMA-gel increased more highly than that of LA-gel. In addition, the methyl group hindered the movement of polymer chains, leading to the lower recovery efficiency of dissipated energy for LMA-gel. In contract, the LA-gel exhibited a rapid response to external force, and possessed better elasticity and self-recovery property. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018 , 56, 1505–1512     

Synthesis and functionalization of dendron‐polymer conjugate based hydrogels via sequential thiol‐ene “click” reactions

Fabrication and functionalization of hydrogels from well‐defined dendron‐polymer‐dendron conjugates is accomplished using sequential radical thiol‐ene “click” reactions. The dendron‐polymer conjugates were synthesized using an azide‐alkyne “click” reaction of alkene‐containing polyester dendrons bearing an alkyne group at their focal point with linear poly(ethylene glycol)‐bisazides. Thiol‐ene “click” reaction was used for crosslinking these alkene functionalized dendron‐polymer conjugates using a tetrathiol‐based crosslinker to provide clear and transparent hydrogels. Hydrogels with residual alkene groups at crosslinking sites were obtained by tuning the alkene‐thiol stoichiometry. The residual alkene groups allow efficient postfunctionalization of these hydrogel matrices with thiol‐containing molecules via a subsequent radical thiol‐ene reaction. The photochemical nature of radical thiol‐ene reaction was exploited to fabricate micropatterned hydrogels. Tunability of functionalization of these hydrogels, by varying dendron generation and polymer chain length was demonstrated by conjugation of a thiol‐containing fluorescent dye. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 926–934     

Inclusion complexes of α‐cyclodextrin and (AB)n block copolymers

Cyclodextrins thread onto polymer chains to form inclusion complexes, especially when the polymer is hydrophobic relative to the solvent. Selective threading might occur when the polymer architecture contains both hydrophobic and hydrophilic segments. α‐Cyclodextrin formed crystalline inclusion complexes with (AB)_n microblock copolymers, where the A block was a linear alkyl segment containing a single double bond and the B block was an exact length segment of poly(ethylene oxide). The complexes were isolated and characterized by solution and solid‐state NMR, X‐ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. Each method confirmed complex formation and showed that the physical properties of the complexes were distinct from those of its individual components. The X‐ray data were consistent with known inclusion complexes having a channel or column crystal structure. The stoichiometry of the complex formation, 2.3 α‐cyclodextrin rings per polymer repeat unit, was determined by NMR analysis of the complexes and from an analysis of the inclusion complex yields. The data suggest that the inclusion complex stoichiometry is defined by the increasing insolubility of the polymer–cyclodextrin complex. Solid‐state NMR data were consistent with a preference for threading onto hydrophobic segments of the (AB)_n polymer. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 2731–2739, 2001     

Fabrication,chemical modification,and topographical patterning of reactive gels assembled from azlactone‐functionalized polymers and a diamine

The work reported here demonstrates an approach to the fabrication of chemically reactive and topographically patterned hydrogels using the azlactone‐functionalized polymer poly(2‐vinyl‐4,4'‐dimethylazlactone) (PVDMA) and the hydrophilic diamine Jeffamine®. Gels were initially assembled in DMSO but can be subsequently transferred into aqueous media to form hydrogels. Spectroscopic characterization of assembled gels demonstrated that variation in the stoichiometric ratio of azlactones to amines during gel synthesis permits control over the extent of crosslinking in the gels. Residual azlactones not consumed during crosslinking can be exploited to further functionalize these gels with hydrophobic, hydrophilic, and macromolecular amines that influence the physicochemical properties of these materials in aqueous solvents. The surface and bulk of these gels can be differentially functionalized (i.e., different functional groups on the gel surface relative to the bulk) by taking advantage of different rates of diffusion of macromolecular amines versus small molecule amines into assembled gels. Finally, these azlactone‐functionalized gels can be topographically patterned with microwell arrays using a replica molding technique and chemically modified postfabrication with amine nucleophiles. This reactive approach to the fabrication of topographically patterned and chemically functionalized hydrogels offers a straightforward method for the rapid synthesis of micropatterned scaffolds of interest in a broad range of applications. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 3185–3194     

Functionalizable biodegradable photocrosslinked elastomers based on 2‐oxepane‐1,5‐dione

The use of aliphatic polyesters for biomedical applications is limited by the lack of functionality of their backbones. The aim of the following study was to develop a novel elastic scaffold material containing functional groups to be used for future derivatization to tether peptide ligands to support cell adhesion, migration, and differentiation. The elastomer was based on three‐arm star copolymers composed of ε‐caprolactone and a functionalized ε‐caprolactone, 2‐oxepane‐1,5‐dione, and end‐terminated with acrylate groups. The elastomer thus contains a ketone and two approaches were examined for obtaining a photocrosslinkable elastomer containing functional groups: crosslinking followed by ketone reduction using sodium borohydride to generate pendant hydroxyl groups, and reaction of the ketone with hydrazines. Reduction of the ketone lead to degradation of the elastomer through transesterification and ethanolate mediated cleavage of the polymer backbone. Reaction with hydrazines did not degrade the polymer and resulted in efficient functionalization of the elastomer. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 8191–8199, 2008     

Thermosensitive lactitol-based polyether polyol (LPEP) hydrogels

A series of new thermosensitive polymer hydrogels were prepared by reacting acylated poly(ethylene glycol) bis(carboxymethyl) ether (PEGBCOCl) with lactitol-based polyether polyols (LPEP). The polyether polyols were generated from propoxylation of lactitol and have molecular weights ranging from 1337 to 4055 g/mol. The hydrogels absorb water up to 1000% of their dry weight and expel free water at temperatures at and above 30°C. The wide ranging swelling behavior and excellent thermosensitivity depend closely on the degree of crosslinking and the propylene oxide lengths in the polyols. Differential scanning calorimetry of the hydrogels showed two endotherms associated with the phase transitions of PO and EO segments in the hydrogel structures. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 979–984, 1998     

Hydrophilic silicone hydrogels with interpenetrating network structure for extended delivery of ophthalmic drugs

In the current work, hydrophilic silicone hydrogels were prepared for extended drug delivery applications. The preparation method was based on sequential interpenetrating network synthesis. A hydrophilic network was prepared by radical copolymerization of hydrophilic monomers 2‐hydroxyethyl methacrylate and poly(ethylene glycol) diacrylate. A hydrophobic silicone network was obtained by crosslinking polymerization of bifunctional methacrylated polydimethylsiloxanes macromonomer. The morphology of the silicone hydrogels was characterized by transmission electron microscopy. The result showed that the silicone hydrogels exhibited heterogeneous morphology. The properties of the silicone hydrogels such as equilibrium swelling ratio (ESR), mechanical property, oxygen permeability, contact angle, and protein repelling ability were investigated. Finally, the silicone hydrogels were loaded with timolol by pre‐soaking in drug solution to evaluate drug‐loading capacity and in vitro release behavior. The results showed that mechanical strength and oxygen permeability increased, and the ESR decreased with the increase of silicone component in the silicone hydrogels. The result of the contact angle measurement indicated that the silicone hydrogels possessed hydrophilic surfaces. The drug loading and in vitro releases were dependent on the composition of hydrophilic/hydrophobic phase of silicone hydrogels. Copyright © 2011 John Wiley & Sons, Ltd.     

Enzymatic‐ and light‐degradable hybrid nanogels: Crosslinking of polyacrylamide with acrylate‐functionalized Dextrans containing photocleavable linkers

Enzymatically cleavable and light‐degradable hybrid nanogels were prepared by free radical inverse miniemulsion copolymerization of acrylamide (AAm) with a newly synthesized functional dextran crosslinker containing acrylate moieties attached to the backbone via a photolabile linker, that is, dextran‐photolabile linker‐acrylate (Dex‐PL‐A). The Dex‐PL‐A/AAm feed ratio was systematically varied to investigate the influence of the particle composition on the gel properties. The resulting hydrogel nanoparticles were examined with regard to their degradation behavior upon the appliance of the two orthogonal stimuli by turbidity measurements in combination with dynamic light scattering. Although continuous photolytic cleavage of the photolabile linkers between polyacrylamide chains and dextran molecules was found to proceed fast and quantitatively yielding completely disintegrated networks, stepwise irradiation resulted in partial degradation of crosslinking points. Thus, nanogels of a desired specific degree of swelling (DGS) can be obtained by adjusting the irradiation time accordingly. Partial enzymatic cleavage of the dextran backbones of the Dex‐PL‐A crosslinking molecules resulted in an increase in the DGS of the nanogels up to a constant value. Subsequent irradiation of those swollen hydrogel particles was used to fully degrade the network structure in a second step. Hence, a two‐step degradation profile was realized by the combination of the two orthogonal stimuli. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012