Interpenetrating Polymer Network Hydrogels Research Articles

Development of visible-light responsive and mechanically enhanced "smart" UCST interpenetrating network hydrogels.

An interpenetrating polymer network (IPN), chlorophyllin-incorporated environmentally responsive hydrogel was synthesized and exhibited the following features: enhanced mechanical properties, upper critical solution temperature (UCST) swelling behavior, and promising visible-light responsiveness. Poor mechanical properties are known challenges for hydrogel-based materials. By forming an interpenetrating network between polyacrylamide (PAAm) and poly(acrylic acid) (PAAc) polymer networks, the mechanical properties of the synthesized IPN hydrogels were significantly improved compared to hydrogels made of a single network of each polymer. The formation of the interpenetrating network was confirmed by Fourier Transform Infrared Spectroscopy (FTIR), the analysis of glass transition temperature, and a unique UCST responsive swelling behavior, which is in contrast to the more prevalent lower critical solution temperature (LCST) behaviour of environmentally responsive hydrogels. The visible-light responsiveness of the synthesized hydrogel also demonstrated a positive swelling behavior, and the effect of incorporating chlorophyllin as the chromophore unit was observed to reduce the average pore size and further enhance the mechanical properties of the hydrogel. This interpenetrating network system shows potential to serve as a new route in developing "smart" hydrogels using visible-light as a simple, inexpensive, and remotely controllable stimulus.

An Injectable Interpenetrating Polymer Network Hydrogel with Tunable Mechanical Properties and Self‐Healing Abilities

AbstractIn this work, a versatile and simple strategy to build an injectable interpenetrating polymer network (IPN) hydrogel with tunable mechanical properties and self‐healing ability is reported. The gelation time and mechanical properties can be tuned by pH or the solid content. Due to the exchange of acylhydrazone and boronate ester bonds formed between functionalized prepolymers, the hydrogels can self‐heal at either acidic or basic condition. Furthermore, the pH‐induced IPN to semi‐IPN reversible transition endows the hydrogels with tunable pore structure and mechanical properties. It is hoped that this novel strategy will provide new opportunities in design and preparation of 3D‐printable IPN hydrogels, fostering their use in a wide range of applications such as controlled drug release and tissue engineering.

Alkaline poly(ethylene glycol)-based hydrogels for a potential use as bioactive wound dressings.

The number of patients with chronic wounds is increasing constantly in today's aging society. However, little work is done so far tackling the associated disadvantageous shift of the wound pH. In our study, we developed two different approaches on pH-modulating wound dressing materials, namely, bioactive interpenetrating polymer network hydrogels based on poly(ethylene glycol) diacrylate/N-vinylimidazole/alginate (named VIx ) and poly(ethylene glycol) diacrylate/2-dimethylaminoethyl methacrylate/N-carboxyethylchitosan (named DMAEMAx ). Both formulations showed a good cytocompatibility and wound healing capacity in vitro. The developed dressing materials significantly increased the cell ingrowth in wounded human skin constructs; by 364% and 313% for the VIx and the DMAEMAx hydrogel formulation, respectively. Additionally, VIx hydrogels were found to be suitable scaffolds for superficial cell attachment. Our research on the material properties suggests that ionic interactions and hydrogen bonds are the driving forces for the mechanical and swelling properties of the examined hydrogels. High amounts of positively charged amino groups in DMAEMAx hydrogels caused increased liquid uptake (around 190%), whereas VIx hydrogels showed a 10-fold higher maximum compressive stress in comparison to hydrogels without ionizable functional groups. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3360-3368, 2017.

Recent Developments in Thiolated Polymeric Hydrogels for Tissue Engineering Applications.

This review focuses on the recent strategy in the preparation of thiolated polymers and fabrication of their hydrogel matrices. The mechanism involved in the synthesis of thiolated polymers and fabrication of thiolated polymer hydrogels is exemplified with suitable schematic representations reported in the recent literature. The 2-iminothiolane namely "Traut's reagent" has been widely used for effectively thiolating the natural polymers such as collagen and gelatin, which contain free amino group in their backbone. The free carboxylic acid group containing polymers such as hyaluronic acid and heparin have been thiolated by using the bifunctional molecules such as cysteamine and L-cysteine via N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide/N-hydroxysuccinimide (EDC/NHS) coupling reaction. The degree of thiolation in the polymer chain has been widely determined by using Ellman's assay method. The thiolated polymer hydrogels are prepared by disulfide bond formation (or) thiol-ene reaction (or) Michael-type addition reaction. The thiolated polymers such as thiolated gelatin are reacted with polyethylene glycol diacrylate for obtaining interpenetrating polymer network hydrogel scaffolds. Several in vitro cell culture experiments indicate that the developed thiolated polymer hydrogels exhibited biocompatibility and cellular mimicking properties. The developed hydrogel scaffolds efficiently support proliferation and differentiation of various cell types. In the present review article, the thiol-functionalized protein-based biopolymers, carbohydrate-based polymers, and some synthetic polymers have been covered with recently published research articles. In addition, the usage of new thiolated nanomaterials as a crosslinking agent for the preparation of three-dimensional tissue-engineered hydrogels is highlighted.

Interpenetrating Alginate-Collagen Polymer Network Microspheres for Modular Tissue Engineering.

The lack of vascularization limits the creation of engineered tissue constructs with clinically relevant sizes. We pioneered a bottom-up process (modular tissue engineering) in which constructs with intrinsic vasculature were assembled from endothelialized building blocks. In this study, we prepared an interpenetrating polymer network (IPN) hydrogel from a collagen-alginate blend and evaluated its use as microspheres in modular tissue engineering. Ionotropic gelation of alginate was combined with collagen fibrillogenesis, and the resulting hydrogel was stiffer and had greater resistance to enzymatic degradation relative to that of collagen alone; the viability of embedded mesenchymal stromal cells (adMSC) was unaltered. IPN microspheres were fabricated by a coaxial air-flow technique, and an additional step of collagen coating was required to have human umbilical vein endothelial cells (HUVEC) attach and proliferate. When implanted subcutaneously in SCID/bg mice, adMSC-HUVEC microspheres promoted more blood vessels at day 7 relative to microspheres without adMSC but coated with HUVEC. Perfusion studies confirmed that these vessels were connected to the host vasculature. Fewer vessels were detected in both groups at day 21, but in adMSC-HUVEC explants, more smooth muscle cells had wrapped around vessels, and CLARITY processing of whole explants revealed a restricted leakage of blood. The capacity for rapid gelation and high throughput production are promising features for the use of these microspheres in modular tissue engineering.

Interpenetrating network hydrogels with high strength and transparency for potential use as external dressings

Interpenetrating polymer network (IPN) hydrogels composed of gelatin and hydroxypropyl cellulose (HPC) were prepared by successive enzymatic and chemical crosslinking approaches. The hydrogels displayed porous structure and the pore size decreased with the increase of HPC content. Due to the entanglement and interpenetrating between the two crosslinked networks, the IPN hydrogels exhibited excellent mechanical strength and light transmittance. The maximum tensile and tear strengths of the IPN hydrogels reached 3.1 and 5.2MPa, respectively. The water vapor permeability of the IPN hydrogels was within the acceptable range to maintain appropriate moisture for wound healing. The cytotoxicity evaluation indicated that the IPN hydrogels exhibited no toxicity to fibroblast cells. In addition, the hydrogels were loaded with chloramphenicol by pre-soaking in drug solutions to evaluate drug-loading capacity and in vitro release behavior. It was found that the drug loaded hydrogels could act as drug delivery devices to create microbe free microenvironment, which was advantageous for wound healing.

Interpenetrating polymer networks hydrogels of chitosan and poly(2-hydroxyethyl methacrylate) for controlled release of quetiapine

Polymer networks interpenetrated by chitosan and 2-hydroxyethyl methacrylate (HEMA) were synthesized. The FTIR spectra confirmed crosslinking of chitosan and polymerization of HEMA. The swelling properties were studied at different pHs and depend particularly on the chitosan content of the material and the pH sensitivity of the network. DSC studies showed two vitreous transitions at approximately 98°C and 155°C, which correspond to the networks of pHEMA and chitosan respectively, demonstrating that the materials obtained are amorphous and interpenetrated. Creep-recovery and stress relaxation studies showed that the materials demonstrate viscoelastic behavior. Quetiapine was used as a pharmacological model for studies of controlled release, and it was found that the process is controlled by diffusion and by relaxation of the polymer network. Finally, the synthesized materials were degraded using lysozyme under simulated physiological conditions. A higher degree of degradation was observed in conjunction with an increase in the chitosan content.

Alginate-polyvinyl alcohol based interpenetrating polymer network for prolonged drug therapy, Optimization and in-vitro characterization

A new natural and synthetic polymeric blend to form interpenetrating polymer network (IPN) hydrogels was synthesized utilizing sodium alginate and PVA as polymers by free radical polymerization employing 2-Acylamido-2-methylpropane-sulfonic acid as monomer (AMPS) and tramadol HCl as model drug through 32 level full factorial design to evaluate the impact of selected independent factors i.e. polymer (sodium alginate) and monomer (AMPS) contents on swelling index at 18th hour, percent drug release at 18th hour, time required for 80% drug release and drug entrapment efficiency as dependent variables. FTIR, SEM, sol-gel analysis, equilibrium swelling studies and in-vitro release kinetics were performedfor in-vitro characterization of formulated IPN hydrogels. In-vitro studies carried out at pH 1.2 and pH 7.4 revealed pH independent swelling and drug release from polymeric IPN, providing controlled drug release for an extended period of time with improved entrapment efficiency, thereby concluding that this polymeric blend may be a promising system for the prolonged drug delivery.

Phosphorylation of chitosan/HEMA interpenetrating polymer network prepared by γ-radiation for metal ions removal from aqueous solutions

Interpenetrating polymer network (IPN) hydrogels, based on chitosan (CS) and 2-hydroxyethyl methacrylate (HEMA), have been prepared by γ-radiation followed by chemical modification via phosphorylation reaction and used for adsorption of Ca(II), Cu(II) and Zn(II) ions from their aqueous solutions. The gel content (%) increases with increasing the HEMA concentration. The maximum swelling (%) observed at the ratio (70/30) (CS/HEMA). CS/pHEMA IPN showed a higher thermal stability than CS. The phosphorylated hydrogel, Phos-(CS/pHEMA), characterized by XRD, EDS, SEM, DSC and TGA techniques. FT-IR spectra before and after adsorption of metal ions have been studied. Factors affecting the maximum adsorption capacity were also investigated. The maximum adsorption capacity using 0.01g Phos-(CS/pHEMA) was 66.3, 57.6 and 48.7 (mg/g) for Cu(II), Zn(II) and Ca(II) ions, respectively. The adsorption isotherms were simulated by Langmuir and Freundlich models and the adsorption kinetics were simulated by the pseudo-first-order and pseudo-second-order kinetics. The adsorption follows Langmuir models and pseudo-second order. The IPN hydrogels showed effective adsorption of the three metal ions from aqueous solution.

High elasticity, strength, and biocompatible amphiphilic hydrogel via click chemistry and ferric ion coordination

An amphiphilic interpenetrating polymer network hydrogel was designed and synthesized using click chemistry and ferric ion coordination. The first polymer network was formed through the reaction of azide-modified PEG (N3-PEGn-N3) and alkynyl-pendant linear PPG derivatives ((PPGm(C≡CH))n) through click chemistry and mixed with poly(ethylene glycol-dopamine) macromolecules. The second polymer network was formed through ferric ion coordination with poly(ethylene glycol-dopamine). Interpenetrating polymer networks give the hydrogel unique amphiphilic properties and higher mechanical strength and thermal stability. Swelling ratio and degradation rate could be adjusted by controlling the ratio of poly(ethylene glycol-dopamine) in the hydrogel network. Given that in vivo subcutaneous implantation revealed no infection and no obvious abnormalities, the hydrogel exhibits high biocompatibility. The feature indicates that these hydrogels have a promising application in the field of biomaterials and tissue engineering. Copyright © 2016 John Wiley & Sons, Ltd.

Enhancing mechanical strength of hydrogels via IPN structure

ABSTRACTIn this investigation, polyacrylamide (PAAm) as the flexible network is introduced to enhance the mechanical strength of hyaluronic acid–gelatin (HA–Gel) hydrogels by interpenetrating polymer network (IPN). The structure, mechanical property, and rheology property of the IPN hydrogels are investigated. It is found that the compressive strength of the HA–Gel/PAAm IPN hydrogels has increased five times higher than that of HA–Gel hydrogels. Rheological test demonstrates that elastic moduli (G′) and viscous moduli (G″) of HA–Gel/PAAm IPN hydrogels increase 100 times higher than those of HA–Gel hydrogels. Moreover, the HA–Gel hydrogels are fractured under the low compressive stress, whereas HA–Gel/PAAm IPN hydrogels are not broken under the high compressive stress. It is envisioned that the IPN hydrogels will be an effective approach to enhance the mechanical strength and broaden the range of hydrogels' applications. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44503.

Synthesis of dual responsive carbohydrate polymer based IPN microbeads for controlled release of anti-HIV drug

The present study aims at preparation of dual responsive interpenetrating polymer network hydrogel microbeads from sodium alginate and functionally modified guar gum. Guar gum was modified by graft copolymerization using N-vinylcaprolactam, the maximum % grafting 123.2, obtained at different optimized conditions. The graft copolymer was blended with sodium alginate to form hydrogel microbeads by emulsion crosslinking method using glutaraldehyde as crosslinker. Zidovudine, an anti-HIV drug was encapsulated with 68% encapsulation efficiency. Fourier transform infrared spectroscopy, 1H nuclear magnetic resonance spectroscopy, scanning electron microscopy, differential scanning calorimetry and X-ray diffraction studies justified the grafting reaction, structure, morphology and polymer-drug interactions, respectively. Swelling studies ascertained that microbeads were potentially sensitive to both pH and temperature. In vitro release studies were investigated in pH 1.2 and 7.4, the release time enhanced up to 34h in pH 7.4 at 37°C.

PH-dependent swelling behaviour of interpenetrating polymer network hydrogels based on poly(hydroxybutyl methacrylate) and poly(2-hydroxyethyl methacrylate)

Interpenetrating polymer network (IPN) hydrogels based on poly(hydroxybutyl methacrylate) (poly(HBMA)) and poly(2-hydroxyethyl methacylate) (poly(HEMA)) were constructed by a sequential IPN method. 1,6-hexanedioldiacrylate (HDDA) was used as a crosslinker and erythrosine/triethanolamine (TEOA) system to initiate radical polymerization after UV light exposure. Effect of pH on the swelling behaviour of these IPNs was investigated. The results showed that the IPN hydrogels exhibited negatively change of swelling behaviour with variation in pH from 2 to 11 and the diffusion of water molecules was caused by the electrostatic attraction between polar groups (–OH) in both IPN and H2O that occur when a hydrogen (H) atom bound to the oxygen (O) which have a high electronegativity. Sample modeling was used to rationalize the experimental results obtained. Good correlation between theoretical and experimental results was mentioned.

Preparation and characterization of biodegradable gelatin-PAAm-based IPN hydrogels for controlled release of maleic acid to improve the solubility of phosphate fertilizers

ABSTRACTIn this study, interpenetrating polymer network (IPN) hydrogel systems including maleic acid (MA) were constituted to improve the solubility of phosphate fertilizers. A series of full and semi-IPN hydrogels were prepared from various gelatin/polyacrylamide mixtures by using two different cross-linkers. The effects of polymer composition on the morphological structures and swelling behaviors of the hydrogels were investigated. The swelling values of all hydrogels were found to be in between 435% and 830%. MA release from load0ed hydrogels was followed and it was determined that MA-loaded hydrogels efficiently decreased pH and improved the solubility of Ca3(PO4)2 in releasing medium.

Elucidating Dynamics of Precoordinated Ionic Bridges as Sacrificial Bonds in Interpenetrating Network Hydrogels

Interpenetrating polymer network (IPN) hydrogels were developed by engineering ionic bridges between carboxylated cellulose nanofibrils (CNFs) and amine-terminated poly(ethylene glycol) (PEG) into a covalent poly(acrylamide) architecture network, and the role of precoordinated CNF–PEG dynamic complexes in the IPN hydrogels viscoelastic dynamics was explored. The results shown that the ionic complexes significantly improved the IPN hydrogels energy dissipation and elastic recovery properties, leading to strain-rate dependent mechanics and notable enhancement in tensile toughness. The uniaxial deformation over a range of strain rates demonstrated that fracture energy peaked at 0.05 s–1 before decreased with further increasing strain rate, consistent with the crack propagation rate result. This straightforward sacrificial bonding strategy validates the hypothesis that elastomers with high toughness and excellent recovery can be achieved by incorporating precoordinated supramolecular associating motifs, which confers control over mechanical properties in a reversible, dynamic, and modular fashion.

Sustained Release of Diltiazem Hydrochloride from Cross-linked Biodegradable IPN Hydrogel Beads of Pectin and Modified Xanthan Gum.

Interpenetrating polymer network hydrogel beads of pectin and sodium carboxymethyl xanthan were prepared by ionotropic gelation with Al(+3) ions and covalent cross-linking with glutaraldehyde for sustained delivery of diltiazem hydrochloride. Fourier transform infrared spectroscopy, X-ray diffraction, differential scanning colorimetry and scanning electron microscopy were used to characterise the hydrogel beads. The swelling of the hydrogel and the release of drug were relatively low in pH 1.2 buffer solutions. However, higher swelling and drug release were observed in pH 6.8 buffer solutions. The carboxyl functional groups of hydrogels undergo ionisation and the osmotic pressure inside the beads increases resulting in higher swelling and drug release in higher pH. The release of drug depends on concentration of polymer, amount and exposure time of cross-linker and drug content in the hydrogel matrices. The present study indicated that the hydrogel beads minimised the drug release in pH 1.2 buffer solutions and to prolong the drug release in pH 6.8 buffer solutions.

Smart Macroporous IPN Hydrogels Responsive to pH, Temperature, and Ionic Strength: Synthesis, Characterization, and Evaluation of Controlled Release of Drugs.

Fast responsive macroporous interpenetrating polymer network (IPN) hydrogels were fabricated in this work by a sequential strategy, as follows: the first network, consisting of poly(N,N-dimethylaminoethyl methacrylate) (PDMAEM) cross-linked with N,N'-methylenebisacrylamide (BAAm), was prepared at -18 °C, the second network consisting of poly(acrylamide) (PAAm) cross-linked with BAAm, being also generated by cryogelation technique. Both single network cryogels (SNC) and IPN cryogels were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and water uptake. The presence of weak polycation PDMAEM endows the SNCs and the IPNs cryogels with sensitivity at numerous external stimuli such as pH, temperature, ionic strength, electric field, among which the first three were investigated in this work. It was found that the initial concentration of monomers in both networks was the key factor in tailoring the properties of IPN cryogels such as swelling kinetics, equilibrium water content (EWC), phase transition temperature and the response at ionic strength. The pore size increased after the formation of the second network, the swelling kinetics in pure water being comparable with that of the SNC, phase transition temperature being situated in the range 35-36 °C for IPN cryogels. The water uptake at equilibrium (WUeq) abruptly increased at pH < 3.0 in the case of SNCs, whereas the response of IPN cryogels at the decrease of pH from 6.0 to 1.0 was strongly dependent on the gel structure, the values of WUeq being lower at a higher concentration of DMAEM in the first network, the monomer concentration in the second network being about 10 wt %. The pH response was very much diminished when the monomer concentration was high in both networks (15 wt % in the first network, and 21 wt % in the second network). The increase of the ionic strength from 0 up to 0.3 M NaCl led to the decrease of the WUeq, for all cryogels, the level of dehydration being higher and faster for the SNC than for the corresponding IPN cryogel. The release of diclofenac sodium (DS), as a model acidic drug, triggered by pH, temperature, and ionic strength from the IPN cryogels was evaluated. A pulsatile release of DS from the IPN cryogels was presented, with a slower release at 34 °C (below VPTT) and a faster release at 37 and 40 °C (above the VPTT).

Thermosensitive Behavior and Antibacterial Activity of Cotton Fabric Modified with a Chitosan-poly(N-isopropylacrylamide) Interpenetrating Polymer Network Hydrogel.

To increase the themosensitive behavior and antibacterial activity of cotton fabric, a series of poly (N-isopropylacrylamide)/chitosan (PNIPAAm/Cs) hydrogels was synthesized by interpenetrating polymer network (IPN) technology using a redox initiator. The IPN PNIPAAm/Cs hydrogel was characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The results indicated that the IPN PNIPAAm/Cs hydrogel has a lower critical solution temperature (LCST) at 33 °C. The IPN hydrogel was then used to modify cotton fabric using glutaric dialdehyde (GA) as a crosslinking agent following a double-dip-double-nip process. The results demonstrated that the modified cotton fabric showed obvious thermosensitive behavior and antibacterial activity. The contact angle of the modified cotton fabric has a sharp rise around 33 °C, and the modified cotton fabric showed an obvious thermosensitive behavior. The bacterial reduction of modified cotton fabric against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were more than 99%. This study presents a valuable route towards smart textiles and their applications in functional clothing.

Rational design of target biomolecule-responsive hydrogels using biomolecular complex crosslinks

Event Abstract Back to Event Rational design of target biomolecule-responsive hydrogels using biomolecular complex crosslinks Takashi Miyata1, 2*, Akifumi Kawamura1, 2* and Tadashi Uragami1, 2* 1 Kansai University, Department of Chemistry and Materials Engineering, Japan 2 Kansai University, Organization for Research and Development of Innovative Science and Technology, Japan Introduction: Stimuli-responsive hydrogels have attracted considerable attention as smart biomaterials because of their many future opportunities in biomedical fields. However, very few studies on biologically stimuli-responsive hydrogels that undergo changes in the volume in response to a target biomolecule, i.e., biomolecule-responsive hydrogels, have been undertaken in spite of their many potential applications to drug delivery systems and molecular diagnostics. We proposed a novel strategy for designing biomolecule-responsive hydrogels, which utilizes biomolecular complexes as dynamic crosslinks that dissociate and associate in response to a target biomolecule[1]. For example, the bioconjugated hydrogels with antigen-antibody and lectin-glycopolymer complex crosslinks exhibited unique biomolecule-responsive swelling/shrinking changes[2]-[5]. This paper describes target biomolecule-responsive hydrogels that undergo changes in the volume in response to target DNA or two antigens. Materials and Methods: Bioconjugated hydrogels with DNA duplex crosslinks (DNA-crosslinked hydrogels) were prepared by the copolymerization of the DNA duplexes with acryloyl groups, acrylamide (AAm) and N, N'-methylenebisacrylamide (MBAA) using redox initiator. Bioconjugated hydrogels with two antigen-antibody complex crosslinks were designed using rabbit γ-immunoglobulin G (IgG), bovine serum albumin (BSA) and their antibodies (goat anti-rabbit IgG, anti-BSA). As first networks, bioconjugated hydrogels with the IgG antigen-antibody complexes were prepared by copolymerization of the antigen-antibody complexes with acryloyl groups, AAm and MBAA using redox initiators. Then the second networks with BSA antigen-antibody complexes were formed by the similar copolymerization within the first networks to obtain bioconjugated hydrogels having an interpenetrating polymer network (IPN) structure with two antigen-antibody complex crosslinks (IgG-BSA IPN hydrogels). Results and Discussion: The swelling ratio of DNA-crosslinked hydrogels strongly depended on the base sequence of single-stranded (ss) DNA (Fig. 1). The investigations into the crosslinking density revealed that their DNA-responsive swelling was attributed to a decrease in their crosslinking density, which was caused by the dissociation of the DNA duplex crosslinks, in the presence of target ssDNA. The swelling ratio of IgG-BSA IPN hydrogels increased more highly in a buffer solution with both IgG and BSA than in a solution with either IgG or BSA alone (Fig. 2). The multiple antigens-responsive swelling of the IPN hydrogels was caused by dissociation of both IgG and BSA antigen-antibody complex crosslinks in the presence of both IgG and BSA. Furthermore, the IPN hydrogels regulated the permeation of a model drug in response to both IgG and BSA. Conclusion: Bioconjugated hydrogels that underwent changes in the volume in response to target DNA and two proteins were strategically designed using biomolecular complex crosslinks. Such biomolecule-responsive hydrogels have many potential applications as smart biomaterials for self-regulated DDS and biomolecular diagnosis.

Fully injectable hydrazone-thiosuccinimide and hydrazone-disulfide interpenetrating polymer network (IPN) hydrogels by kinetically orthogonal cross-linking of functionalized poly(N-isopropylacrylamide) (PNIPAM) and poly(1-vinyl-2-pyrrolidone) (PVP) precur

Event Abstract Back to Event Fully injectable hydrazone-thiosuccinimide and hydrazone-disulfide interpenetrating polymer network (IPN) hydrogels by kinetically orthogonal cross-linking of functionalized poly(N-isopropylacrylamide) (PNIPAM) and poly(1-vinyl-2-pyrrolidone) (PVP) precur Trevor Gilbert1 and Todd R. Hoare1* 1 McMaster University, Chemical Engineerin, Canada Introduction: IPNs are produced by interlocking two chemically distinct networks in each other’s free volume fraction. This interlocking and the potential for segregation of the IPNs into inhomogeneous domains can cause mechanical properties and microstructures distinct from single network controls. Prior IPNs reported as injectable (desired for minimally invasive delivery) were polymerized in situ with cross-linkers[1], raising potential concerns of high temperature / UV initiation / chemical toxicity[2]. Networks may instead be formed by simple mixing of injected functionalized polymers[2]. To thus produce an IPN, the two bonding reactions must be highly specific, such as hydrazide-aldehyde with thiol-maleimide[3] or the slower thiol to disulfide reaction. Materials and Methods: Hydrogel IPNs were based on thermosensitive PNIPAM functionalized to produce hydrazones and hydrophilic networks produced from PVP-thiol and -maleimide (Figure 1). Samples were characterized by shear rheometry, freeze-fracture SEM and small-angle neutron scattering (SANS). Thermoresponsive swelling, network degradation and model drug release were evaluated. Results and Discussion: Polymer concentrations were chosen to match storage moduli of single network PNIPAM and PVP controls. IPNs showed enhanced (p<0.05) G’ relative both to the sum of the single networks and to semi-IPN controls with one linear polymer embedded in the other network (Figure 2), attributed to elastic interlocking of the two distinct networks, and suggesting IPN hydrogels as potential reinforced tissue engineering scaffolds. SEM and SANS studies showed differences in IPN microstructure, particularly dependent on the cross-linking rate of the PVP network relative to hydrazone formation in the PNIPAM one, with slower gelling disulfides permitting more phase separation than the faster thiosuccinimide cross-linking. The IPN reflects the PNIPAM component’s LCST behaviour, but with slower transitions and reduced hysteresis after the initial thermal cycle (Figure 3a,b), attributed to the PVP phase’ elastic contribution to re-swelling. Hydrolytic degradation in the IPN is also both slower and less extensive overall (Figure 3c,d), with IPNs retaining their shape and at least half their initial mass weeks longer than the single network controls in an accelerated hydrolysis model. Conclusions: Distinctive mechanical and thermoresponsive behaviour and degradation kinetics between IPN, semi-IPN and single network hydrogels clearly demonstrate the effects of network interpenetration on biomaterial properties. Interlocking also modulates the hydrogel microstructure, dependent on rates of crosslinking between the constitutive networks. We anticipate utility for these hydrogels as reinforced tissue engineering scaffolds, and for reducing burst release in hydrogel drug loading[4],[5], wherein the initial de-swelling typically elutes a large proportion of stored drug by convection.