The influence of diffusion time on the properties of sequential interpenetrating PEG hydrogels

Four sets comprising a total of 16 sequential interpenetrating network (SeqIPN) hydrogels were efficiently fabricated via UV initiated thiol‐ene coupling chemistry and from 2 kDa or 8 kDa primary poly(ethylene glycol) (PEG) networks (S2 and S8). Each primary system delivered four different SeqIPNs constructed after 2, 4, 20, and 44 h diffusion of secondary network PEG precursors, 2 kDa and 8 kDa. This allowed the assessment of both mechanical and swelling properties for a wide range of novel hydrogels ranging from loosely crosslinked SeqIPN 8‐8 to densely crosslinked SeqIPN 2‐2 systems. All gel fractions of secondary networks were above 83% and 44 h of diffusion was found sufficient to fully saturate the primary networks. Disperse red functionalized PEGs (2 kDa and 8 kDa) were further used as probes to investigate the diffusion mechanisms. The impact of diffusion time on loosely crosslinked S8 network with a swelling degree of 970% and tensile modulus of 175 kPa displayed a significant change in the final properties. For instance, a 2 h diffusion of 2 kDa PEG precursors generated a SeqIPN 8‐2:2 comprising a secondary network solid content of 34% with a water swelling degree 580% and a tensile modulus of 365 kPa. On saturation, that is, 44 h of diffusion, SeqIPN 2‐8:44 exhibited 64% of secondary network solid content, a swelling capacity of 380% and over fourfold of tensile modulus (758 kPa) when compared with the primary network S8. SeqIPN hydrogel with the highest tensile modulus and lowest degree of water swelling was obtained after 44 h diffusion of 2 kDa PEG precursors within the densely crosslinked S2 primary network. In this case, SeqIPN 2‐2:44 noted a water swelling capability of 280% and a tensile modulus over 1 MPa. The latter was twofold when compared with S2 with a tensile modulus of 555 kPa. Consequently, the diffusion time of secondary network is a promising parameter to control and that enables the fabrication of PEG hydrogels with a wider window of mechanical and swelling properties. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Poly(2‐oxazoline) hydrogels crosslinked with aliphatic bis(2‐oxazoline)s: Properties,cytotoxicity, and cell cultivation

A series of hydrogels from 2‐ethyl‐2‐oxazoline and three bis(2‐oxazoline) crosslinkers—1,4‐butylene‐2,2′‐bis(2‐oxazoline), 1,6‐hexamethylene‐2,2′‐bis(2‐oxazoline), and 1,8‐octamethylene‐2,2′‐bis(2‐oxazoline)—are prepared. The hydrogels differ by the length of aliphatic chain of crosslinker and by the percentage of crosslinker (2–10%). The influence of the type and the percentage of the crosslinker on swelling properties, mechanical properties, and state of water is studied. The equilibrium swelling degree in water ranges from 2 to 20. With a proper selection of the crosslinker, Young's modulus can be varied from 10 kPa to almost 100 kPa. To evaluate the potential for medical applications, the cytotoxicity of extracts and the contact toxicity toward murine fibroblasts are measured. The hydrogels with the crosslinker containing a shorter aliphatic exhibit low toxicity toward fibroblast cells. Moreover, the viability and the proliferation of pancreatic β‐cells incubated inside hydrogels for 12 days are analyzed. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1548–1559     

Swelling behavior and network structure of hydrogels synthesized using controlled UV‐initiated free radical polymerization

N‐vinyl‐2‐pyrrolidone (VP) and 2‐hydroxyethyl methacrylate (HEMA) copolymeric gels have been synthesized using UV‐initiated photopolymerization to understand their characteristic behavior for development as a bioengineering material, specifically for tissue expansion. The properties of the gels have been investigated by systematic variation of the monomer feed composition and initiator and crosslinker concentrations as well as UV irradiation intensity, which was controlled by various photomasks. The swelling kinetics and network characteristics for the various hydrogels were investigated through the observation of gel swelling behavior in saline solutions and compression modulus determination of the fully swollen hydrogels. The equilibrium swelling ratio (q_e) of the gels increased as expected with increasing VP content and decreasing crosslinker concentration. However, it was found that as the amount of initiator or UV intensity increased, unexpectedly q_e also increased, which indicates a network structure with decreasing effective crosslink density (ν_e) (or increasing average molecular weight between crosslinks (M_c)). Based on this anomalous swelling behavior and thermal analysis of the gels, a molecular structure is proposed consisting of increasing number of dangling chain ends within the polymer network. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 1450–1462, 2008     

Semi‐interpenetrating polymer networks composed of poly(N‐isopropyl acrylamide) and polyacrylamide hydrogels

Three series of semi‐interpenetrating polymer networks, based on crosslinked poly(N‐isopropyl acrylamide) (PNIPA) and 1 wt % nonionic or ionic (cationic and anionic) linear polyacrylamide (PAAm), were synthesized to improve the mechanical properties of PNIPA gels. The effect of the incorporation of linear polymers into responsive networks on the temperature‐induced transition, swelling behavior, and mechanical properties was studied. Polymer networks with four different crosslinking densities were prepared with various molar ratios (25:1 to 100:1) of the monomer (N‐isopropyl acrylamide) to the crosslinker (methylenebisacrylamide). The hydrogels were characterized by the determination of the equilibrium degree of swelling at 25 °C, the compression modulus, and the effective crosslinking density, as well as the ultimate hydrogel properties, such as the tensile strength and elongation at break. The introduction of cationic and anionic linear hydrophilic PAAm into PNIPA networks increased the rate of swelling, whereas the presence of nonionic PAAm diminished it. Transition temperatures were significantly affected by both the crosslinking density and the presence of linear PAAm in the hydrogel networks. Although anionic PAAm had the greatest influence on increasing the transition temperature, the presence of nonionic PAAm caused the highest dimensional change. Semi‐interpenetrating polymer networks reinforced with cationic and nonionic PAAm exhibited higher tensile strengths and elongations at break than PNIPA hydrogels, whereas the presence of anionic PAAm caused a reduction in the mechanical properties. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 3987–3999, 2004     

Sequential interpenetrating poly(ethylene glycol) hydrogels prepared by UV‐initiated thiol–ene coupling chemistry

Poly(ethylene glycol) (PEG)‐diallyls, ranging from 2 to 8 kDa, were successfully reacted with a trifunctional thiol crosslinker via thiol–ene coupling reaction to construct four different primary PEG hydrogels. These systems were used as scaffolds for the preparation of a library of sequential interpenetrating networks (SeqIPNs). The solid content of the secondary networks varied between 21 and 34% and was dependent on the length of the absorbing PEGs. The gel fractions for the IPNs were above 85%. Additionally, the lowest degree of swelling was found for the IPN based on 2‐kDa PEG (315%), whereas the 8‐kDa PEG IPN exhibited a value of 810%. The SeqIPN strategy facilitated hydrogel systems that cover a larger domain of tensile modulus (192–889 kPa) when compared with single hydrogel networks (175–555 kPa). © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Nanocomposite hydrogel consisting of Na‐montmorillonite with enhanced mechanical properties

A new kind of nanocomposite (NC) hydrogel with Na‐montmorillonite (MMT) is presented in this article. The NC hydrogels were synthesized by free radical copolymerization of acrylamide and (3‐acrylamidopropyl) trimethylammonium chloride (ATC) in the presence of MMT and N,N′‐methylene‐bis‐acrylamide used as chemical cross‐linker. Due to the cation‐exchange reaction between MMT and ATC (cationic monomer) during the synthesis of NC hydrogels, MMT platelets were considered chemical “plane” cross‐linkers, different from “point” cross‐linkers. With increasing amount of MMT, the crosslinking degree enhanced, causing a decrease of the swelling degree at equilibrium. Investigations of mechanical properties indicated that NC hydrogels exhibited enhanced strength and toughness, which resulted from chemical interaction between exfoliated MMT platelets and polymer chains in hydrogels. Dynamic shear measurements showed that both storage modulus and loss modulus increased with increasing MMT content. The idea described here provided a new route to prepare hydrogels with high mechanical properties by using alternative natural Na‐MMT. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 1020–1026     

A pH‐sensitive water‐soluble N‐carboxyethyl chitosan/poly(hydroxyethyl methacrylate) hydrogel as a potential drug sustained release matrix prepared by photopolymerization technique

Biocompatible pH‐sensitive semi‐interpenetration polymeric network hydrogels (semi‐IPN) based on water‐soluble N‐carboxyethyl chitosan (CECS) and 2‐hydroxyethyl methacrylate (HEMA) were synthesized by the photopolymerization technique. pH‐sensitivity, cytotoxicity, morphology, mechanical property, and water state of hydrogel were investigated by a swelling test, methylthiazolydiphenyl‐tetrazolium bromide (MTT) assay, scanning electron microscopy (SEM), universal testing machine, and differential scanning calorimetry (DSC), respectively. The drug release studies were carried out using 5‐Flurouracil as the model drug. The results indicated that the hydrogels were sensitive to pH of the medium and its wet state had good mechanical properties. The results of cytotoxicity and prolonged drug release characteristics revealed the suitability of the hydrogels as drug delivery matrices. The release kinetics was evaluated by fitting the experimental data to standard release equations, and the best fit was obtained with the Higuchi model of the hydrogel. Copyright © 2008 John Wiley & Sons, Ltd.     

pH/temperature double responsive behaviors and mechanical strength of laponite‐crosslinked poly(DEA‐co‐DMAEMA) nanocomposite hydrogels

A nanocomposite (NC) hydrogel crosslinked by inorganic Laponite XLG was successfully synthesized via in situ free radical polymerization of monomers N,N‐diethylacrylamide and (2‐dimethylamino) ethyl methacrylate (DMAEMA). Polymerization was carried out at room temperature due to the accelerating effect of DMAEMA. The as‐prepared hydrogels displayed controlled transformation in optical transmittance and volume in response to small diversification of environmental factors, such as temperature and pH. The compressive strength of swollen D_6:1G₆ hydrogels was as high as 2219 kPa while compressive strain was 95%. Cyclic compression measurement exhibited good elastic properties of NC hydrogels. This work provides a facile method for fabricating stimuli‐responsive hydrogels with superior mechanical property. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 876–884     

Light‐Induced Disintegration of Robust Physically Cross‐Linked Polymer Networks

Photodegradable physically cross‐linked polymer networks are prepared from self‐assembly of photolabile triblock copolymers. Linear triblock copolymers composed of poly (o‐nitrobenzyl methacrylate) and poly(ethylene glycol) (PEG) segments of variable molecular weights were synthesized using atom transfer radical polymerization. Triblock polymers with low‐molecular‐weight PEG segments form solid films upon hydration with robust mechanical properties including a Young's modulus of 76 ± 12 MPa and a toughness of 108 ± 31 kJ m⁻³. Triblock polymers with high‐molecular‐weight PEG segments form physically cross‐linked hydrogels at room temperature with a dynamic storage modulus of 13 ± 0.6 kPa and long‐term stability in hydrated environments. Both networks undergo photodegradation upon irradiation with long wave UV light.

     

Synthesis and characterization of novel biodegradable unsaturated poly(ester amide)/poly(ethylene glycol) diacrylate hydrogels

A series of novel biodegradable hydrogels were designed and synthesized from four types of unsaturated poly(ester amide) (UPEA) and poly(ethylene glycol) diacrylate (PEG‐DA) precursors by UV photocrosslinking. These newly synthesized biodegradable UPEA/PEG‐DA hydrogels were characterized by their gel fraction (G_f), equilibrium swelling ratio (Q_eq), compressive modulus, and interior morphology. The effect of the precursor feed ratio (UPEAs to PEG‐DA) on the properties of the hydrogels was also studied. The incorporation of UPEA polymers into the PEG‐DA hydrogels increased their hydrophobicity, crosslinking density (denser network), and mechanical strength (higher compressive modulus) but reduced Q_eq. When different types of UPEA precursors were coupled with PEG‐DA at the same feed ratio (20 wt %), the resulting hydrogels had similar Q_eq values and porous three‐dimensional interior morphologies but different G_f and compressive modulus values. These differences in the hydrogel properties were correlated to the chemical structures of the UPEA precursors; that is, the different locations of the >C?C< double bonds in individual UPEA segments resulted in their different reactivities toward PEG‐DA to form hydrogels. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 3932–3944, 2005     

Photocrosslinked methacrylated poly(vinyl alcohol)/hydroxyapatite nanocomposite hydrogels with enhanced mechanical strength and cell adhesion

Poly(vinyl alcohol) (PVA) hydrogels with high water content, good load‐bearing property, low frictional behavior as well as excellent biocompatibility have been considered as promising cartilage replacement materials. However, the lack of sufficient mechanical properties and cell adhesion are two critical barriers for their application as cartilage substitutes. To address these problems, herein, methacrylated PVA with low degree of substitution of methacryloyl group has been synthesized first. Then, methacrylated PVA‐glycidyl methacrylate/hydroxyapatite (PVA‐GMA/Hap) nanocomposite hydrogels have been developed by the photopolymerization approach subsequently. Markedly, both pure PVA‐GMA hydrogel and PVA‐GMA/Hap nanocomposite hydrogels exhibit excellent performance in compressive tests, and they are undamaged during compressive stress–strain tests. Moreover, compared to pure PVA‐GMA hydrogels, 8.5‐fold, 7.4‐fold, and 14.2‐fold increase in fracture stress, Young's modulus and toughness, respectively, can be obtained for PVA‐GMA/Hap nanocomposite hydrogels with 10 wt % Hap nanoparticles. These enhancements can be ascribed to the intrinsic property of PVA‐GMA and strong hydrogen bonding interactions between PVA‐GMA chain and Hap nanoparticles. More interestingly, significant improvement in the cell adhesion can also be successfully achieved by incorporation of Hap nanoparticles. These biocompatible nanocomposite hydrogels have great potential to be used as cartilage substitutes. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1882–1889     

Thermoresponsive properties of porous poly(N‐isopropylacrylamide) hydrogels prepared in the presence of nanosized silica particles and subsequent acid treatment

Porous poly(N‐isopropylacrylamide) hydrogels were prepared by the free‐radical polymerization of its monomer and a suitable crosslinker in the presence of spherical silica particles of different sizes (74 and 1600 nm) and by the subsequent acid extraction of silica. The yields were 81–83%, and the yields were not affected by the silica content. Scanning electron microscopy observations revealed the porous structure of the hydrogels. Porous and nonporous hydrogels showed volume phase transitions from swelling states to deswelling states at approximately 30 °C, as analyzed by the ratio of the diameter of cylinder‐shaped hydrogels to that of the glass tube used for the hydrogel preparation at the corresponding temperature. Deswelling, which was analyzed by rapid changes in the temperature of the aqueous media from 20 to 40 °C, was facilitated by decreased silica particle size and increased silica content. The deswelling rate constant of the hydrogel prepared with 74‐nm silica at 10 v/v % (silica/solvent) was more than 1500 times greater than that of conventional hydrogels. Swelling was similarly analyzed through changes in the temperature from 40 to 20 °C and was independent of the pore structure. The deswelling–swelling cycle was repeatable with reasonable reproducibility. Moreover, the mechanical strength of the porous hydrogels was significantly maintained compared with that of conventional nonporous hydrogels. This method produced thermoresponsive hydrogels of suitable mechanical strength and remarkable deswelling properties. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 4228–4235, 2002     

pH and reduction dual‐stimuli‐responsive PEGDA/PAMAM injectable network hydrogels via aza‐michael addition for anticancer drug delivery

A pH and reduction dual‐stimuli‐responsive PEGDA/PAMAM injectable network hydrogel containing “acetals” as pH‐sensitive groups and “disulfides” as reducible linkages was designed and synthesized via aza‐Michael addition reaction between PAMAM and PEGDA diacrylates. The pore size and swelling ratio of hydrogels was varied from 14 ± 3 to 19 ± 4 μm and 214 ± 13 to 300 ± 19 μm, respectively, with varying ethylene glycol repeating units in diacrylates. The swelling ratio of PEGDA/PAMAM network hydrogel increased with increase in the molecular weight of PEG and with decrease in pH. The presence of different cationizable amino‐functionalities in PEGDA/PAMAM network hydrogel helped to enhance the swelling ability of hydrogel under the acidic conditions. The continuous increase in metabolically active live HeLa cells with time in MTT assay implied biocompatibility/noncytotoxicity of the synthesized PEGDA/PAMAM injectable network hydrogel. Furthermore, the prepared PEGDA/PAMAM hydrogel showed higher degradation at lower pH and at higher concentration of DTT. The burst release of doxorubicin from PEGDA/PAMAM hydrogel under the environment of the lower pH and in presence of DTT compared to the release at normal physiological pH and in absence of DTT suggested the potential ability of this model hydrogel system for targeted and selective anticancer drug release at tumor tissues. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 2080–2095     

Triple redox/temperature responsive diselenide‐containing homopolypeptide micelles and supramolecular hydrogels thereof

Stimuli‐responsive polypeptides are receiving much attention for drug delivery systems and tissue engineering scaffolds; however, it is challenging to construct multiple‐responsive polypeptides and one‐component polymeric hydrogels. Herein, a novel type of triple redox/temperature‐responsive diselenide‐containing poly(methoxydiethylene glycol‐l ‐glutamate) homopolypeptide was facilely synthesized by selenocystamine‐initiated ring‐opening polymerization in DMF at 30 °C, and their chemical structures and physical properties were fully characterized by means of ¹H NMR, GPC, FT‐IR, WAXD, and CD. They self‐assembled into spherical micelles in aqueous solution, which possess a lower critical solution temperature, redox‐responsiveness inherited from diselenide bond, and the triple stimuli‐sensitive self‐assembly behaviors, as characterized by means of turbidity, DLS, TEM, and zeta potential measurements. The diselenide‐containing homopolypeptides formed supramolecular hydrogels at room temperature, exhibiting a thermal gel–sol transition. The rheological tests evidence that the mechanical modulus of the hydrogel is independent of angular frequency within 100 rad/s and at 25 °C, in which the storage modulus of G′ is order of magnitude greater than the loss modulus of G″, displaying a solid‐like elastic behavior. Moreover, the mechanical modulus of the hydrogel can be tuned by changing the chain length of the homopolypeptide, the 10‐mM 1,4‐dithiothreitol (DTT) reduction, and 1 mM H₂O₂ oxidation, respectively. Consequently, this work provides a simple strategy to fabricate triple‐stimuli responsive polypeptide micelles and one‐component hydrogels. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 1067–1077     

Compressive Elastic Moduli of Poly(N‐Isopropylacrylamide) Hydrogels Crosslinked with Poly(Dimethyl Siloxane)

Hydrophobically modified and thermally reversible neutral and ionic copolymer hydrogels were prepared from N‐isopropylacrylamide (NIPAAm), vinyl terminated poly (dimethylsiloxane) (VTPDMS) and itaconic acid (IA) by free radical solution polymerization, and their properties such as swelling ratio and compression modulus were studied at the 25°C. The incorporation of VTPDMS as a hydrophobic macrocrosslinker into the structures of neutral NIPAAm hydrogels increased their mechanical strength around 10 times than those of the ones crosslinked with conventional tetra functional monomer, i.e., N,N′‐methylene bisacrylamide (BIS). Compression modulus decreased with an increase in IA content for ionic samples and increased with increasing molecular weight and content of VTPDMS for neutral samples. It was assumed that in the first case, electrostatic repulsive forces resulting from the ionized carboxyl groups of IA were responsible for decreasing mechanical strength, while in the second case, hydrophobic interactions between dimethylsiloxane units of VTPDMS chains enhanced the compression moduli. According to the results presented in this work, it can be said that the right balance of hydrophobic and hydrophilic constituents and adjustment of the number of ionized groups, as well as crosslinking degree, change the structure and physical properties of NIPPAAm hydrogels.     

Shear modulus determination in model hydrogels by means of elongated magnetic nanoprobes

The mechanical characterization of complex soft matter by quasi-static magnetometry using nanoscopic magnetic probes is demonstrated for model hydrogels doped with two types of elongated magnetic nanoparticles. Chemically crosslinked poly(acrylamide) (PAAm) hydrogels serve as the matrix in which nickel nanorods or weakly magnetized hematite (α-Fe₂O₃) ellipsoids are embedded as local probes. We investigated the swelling behavior of the ferrogels in order to verify that their equilibrium swelling degree in water is not influenced by the probes, shows a good correlation with the Frenkel–Flory–Rehner model. The proposed magnetomechanical method relies on a correlation between the shear modulus of the PAAm hydrogel matrix and the coercive fields of the corresponding isotropic ferrogels. By extending the Stoner–Wohlfarth model for single-domain blocked magnetic particles by a term for particle rotation in an elastic matrix, information on the shear modulus of the matrix can be obtained. Comparison of the results with the expected relation from rubber elasticity theory illustrates both the general potential as well as the limits of the approach. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012     

Using hydrophobic additive as pore‐forming agent to prepare macroporous PNIPAAm hydrogels

Hydrophobic poly(lactic acid) nanospheres were fabricated and used as an additive during the polymerization and gelation process of temperature‐sensitive poly(N‐isopropylacrylamide) (PNIPAAm) hydrogels. The influence of hydrophobic additive on properties of PNIPAAm hydrogels was examined. The interior morphology studied by scanning electron microscopy revealed that the hydrophobic additive induced a macroporous structure in the resulting PNIPAAm hydrogels. Results demonstrate that the hydrophobic additive acts as a pore‐forming agent like conventionally used hydrophilic additive does during the gelation process. Because of the macroporous network and incorporated additives, the temperature‐sensitive characteristics, particularly the equilibrium swelling ratio at room temperature and shrinking rate upon temperature increase of modified PNIPAAm hydrogels, are significantly improved. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5490–5497, 2005     

Synthesis of poly(ethylene glycol)‐based hydrogels and their swelling/shrinking response to molecular recognition

To synthesize the novel molecular‐ and pH‐stimulus‐responsive hydrogel, we prepared poly(ethylene glycol)‐based hydrogel containing ionic groups. We evaluated the fundamental swelling/shrinking properties of the hydrogels synthesized by various conditions. Decreasing the molecular weight of a crosslinker provided the increasing of the equilibrium swelling ratio. Also, the equilibrium swelling ratio was changed by the introduction of functional ionic monomers and its compositions. Furthermore, the swelling/shrinking behaviors of the hydrogels were affected by the environmental condition of aqueous solution, in fact the hydrogels were considerably shrunk (to one‐fifth volume) using a di‐ionic solute in the aqueous solution through the ionic interactions between the hydrogel and the solutes. Additionally, the specific shrinking to diamine compounds was also observed in response to pH change. These results clearly show the swelling/shrinking responsibility of the hydrogels toward the molecular recognitions and its pH conditions. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3153–3158     

Drug‐Loaded Elastin‐Like Polypeptide–Collagen Hydrogels with High Modulus for Bone Tissue Engineering

Emphasizing the role of hydrogel stiffness and cellular differentiation, this study develops collagen and elastin‐like polypeptide (ELP)–based bone regenerative hydrogels loaded with recombinant human bone morphogenetic protein‐2 (rhBMP‐2) and doxycycline with mechanical properties suitable for osteogenesis. The drug‐incorporated collagen–ELP hydrogels has significantly higher modulus of 35 ± 5 kPa compared to collagen‐only hydrogels. Doxycycline shows a bi‐phasic release with an initial burst release followed by a gradual release, while rhBMP‐2 exhibits a nearly linear release profile for all hydrogels. The released doxycycline shows anti‐microbial activity against Pseudomonas aeruginosa, Streptococcus sanguinis, and Escherichia coli. Microscopic observation of the hydrogels reveals their interconnected, macroporous, 3D open architecture with pore diameters between 160 and 400 µm. This architecture supports human adipose–derived stem cell attachment and proliferation from initial days of cell seeding, forming a thick cellular sheath by day 21. Interestingly, in collagen and collagen–ELP hydrogels, cell morphology is elongated with stretched slender lamellipodial formation, while cells assemble as spheroidal aggregates in crosslinked as well as drug‐loaded hydrogels. Osteogenic markers, alkaline phosphatase and osteocalcin, are expressed maximally for drug‐loaded hydrogels compared to those without drugs. The drug‐loaded collagen–ELP hydrogels are thus promising for combating bacterial infection and promoting guided bone regeneration.     

Synthesis and Characterization of pH‐sensitive Poly(IA‐co‐AAc‐co‐AAm) Hydrogels via Frontal Polymerization

In this work, we report a series of poly(itaconic acid‐co‐acrylic acid‐co‐acrylamide) (poly(IA‐co‐AAc‐co‐AAm)) hydrogels via frontal polymerization (FP). FP starts on the top of the reaction mixture with aid of heating provided from soldering iron gun. Once polymerization initiated, no further energy is required to complete the process. The influences of IA/AAc weight ratios on frontal velocities, temperatures, and conversions on the reaction time are thoroughly investigated and discussed where the amount of AAm monomer remains constant. Fourier transform‐infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscope (SEM), dynamic mechanical analysis, and the swelling measurement are applied to characterize the as‐synthesized poly(IA‐co‐AAc‐co‐AAm) hydrogels. Interestingly, the swelling ratios of the hydrogels are changed with different IA/AAc contents, and the maximum swelling ratios are ~4439% in water. SEM images describe highly porous morphologies and explain good swelling capabilities. Moreover, the poly(IA‐co‐AAc‐co‐AAm) hydrogels exhibit superior pH‐responsive ability. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 2214–2221