Interpenetrating Polymer Network Hydrogels Research Articles

Ion-conductive self-healing hydrogels based on an interpenetrating polymer network for a multimodal sensor

Conductive self-healing polymer hydrogel and related soft sensor devices are receiving considerable attention from academia to industry because of their impacts on the lifetime and ergonomic design of soft robotics, prosthesis, and health monitoring systems. However, the development of such a material has thus far been limited considering performances and accessibility. Herein, robustness, self-healing, and conductivity for soft electronic skin are realized by an interpenetrating polymer network (IPN) system based on chemical/ionic cross-linked poly(acrylic acid) containing ferric ions, intercalated with physically cross-linked poly(vinyl alcohol). This IPN hydrogel successfully satisfies all three aforementioned capabilities; elongation at break greater than 1400%; recovery to original mechanical properties greater than 80% after 24 h; and 0.14 S m−1 of ionic conductivity, which is electrically healable. Such ionic conductivity of hydrogels enables multimodal sensing capabilities, i.e., for strain, pressure, and temperature. Particularly, a uniquely designed dual sensor attached to a finger simultaneously detects mechanical folding and pressure changes independently and can undergo large deformation 1000 times repeated and heating up to 90 °C.

Interpenetrating Polymer Network Hydrogels of Gelatin and Poly(ethylene glycol) as an Engineered 3D Tumor Microenvironment

An emerging trend in cancer research is to develop engineered tumor models using bio-inspired biomaterials that can mimic the native tumor microenvironment. Although various bio-inspired hydrogels have been utilized, it is still challenging to develop advanced polymeric hydrogel materials that can more accurately reconstruct critical aspects of the native tumor microenvironment. Herein, we present interpenetrating polymer network (IPN) hydrogels composed of thiolated gelatin and tyramine-conjugated poly(ethylene glycol), which form IPN hydrogels via horseradish peroxidase-mediated dual cross-linking reactions. We demonstrate that the IPN hydrogels exhibit independently controllable physicochemical properties. Also, the IPN hydrogels show resistance to the proteolytic enzymes and cytocompatibility for long-term culture of human fibrosarcoma (HT1080) cells. Moreover, we utilize the engineered tumor construct as a platform to evaluate the effect of matrix stiffness on cancer cell proliferation and drug resistance against the anticancer drug 5-fluorouracil as a model drug. In conclusion, we suggest that our IPN hydrogel is a promising material to study cancer biology and to screen innovative therapeutic agents for better clinical outcomes.

Cell-laden interpenetrating network hydrogels formed from methacrylated gelatin and silk fibroin via a combination of sonication and photocrosslinking approaches

The regeneration of load-bearing soft tissues has long driven the research and development of bioactive hydrogels. A major challenge facing the application of hydrogels to load-bearing tissues is the development of hydrogels with appropriate biological functionality and biomechanical stability that closely mimic the host tissue. In this paper, we describe a newly synthesized cell-laden interpenetrating polymer network (IPN) hydrogel based on gelatin methacrylate (GelMA) and silk fibroin (SF) that was formed via sequential sonication and photocrosslinking. The experimental results revealed that SF-GelMA IPN hydrogels exhibited high swelling ratios, excellent mechanical properties, resistance to enzymatic degradation by collagenase, and porous internal microstructures. Moreover, these properties could be tailored by changing the prepolymer components. MC3T3-E1 pre-osteoblasts attached to and subsequently proliferated on the IPN hydrogels, as demonstrated by fluorescein diacetate/propidium iodide (FDA/PI) staining and Cell Counting Kit-8 (CCK-8) analysis. In addition, the encapsulation of MC3T3-E1 pre-osteoblasts and a subsequent cell viability assay demonstrated that the entire IPN formation process was compatible with cells and that the growth of encapsulated cells could be tuned by adjusting the GelMA concentration, underlining their versatility for various load-bearing soft tissue engineering. Overall, this study introduces a class of mechanically robust and tunable cell-laden IPN hydrogels which have great potential as load-bearing soft tissue engineering scaffold.

Carboxymethyl cellulose/poly(acrylic acid) interpenetrating polymer network hydrogels as multifunctional adsorbents

Interpenetrating polymer network (IPN) hydrogels were prepared by mixing carboxymethyl cellulose (CMC) solution and crosslinked poly(acrylic acid) (cPAA) single IPN hydrogel at mass ratios 100:0, 25:75, 50:50, 75:25 and 0:100 and subsequent crosslinking of CMC chains with citric acid, aimed towards the creation of full IPN hydrogels. The resulting CMC:cPAA hydrogels were freeze-dried for the determination of density, swelling degree, compressive modulus and thermal behavior. Morphological and structural parameters were determined by means of scanning electron microscopy, Fourier transform infrared spectroscopy in the attenuated total reflectance mode (FTIR-ATR) and X-ray microtomography (CT) analyses. The efficiency of CMC:cPAA hydrogels as adsorbents for methylene blue (MB) dye at pH 7 and Cu2+ ions at pH 4.5 was systematically investigated at (24 ± 1) °C and evaluated with Langmuir, Freundlich and Dubinin–Radushkevitch adsorption models and kinetic equations. The CMC:cPAA 50:50 hydrogels were particularly interesting because they presented the highest compression modulus (141 ± 3 kPa), swelling degree of 58 ± 2 gwater/g and maximum adsorption capacity (qmax) for MB dye and Cu2+ ions as 613 mg g−1 and 250 mg g−1, respectively. The adsorption kinetics of MB and Cu2+ ions followed the pseudo-second order equation. Fitting with the intraparticle diffusion model showed that in both cases, the adsorbate molecules first diffuse rapidly from the medium to the adsorbent surface, and then in a second slower stage, they diffuse into the network macropores. The hydrogels could be recycled five times without losing efficiency.

Antioxidant Activity of Dopamine-Modified Hydrogels Containing Cross-linked Hyaluronic Acid

Purpose : : In this study, we made dopamine-functionalized hydrogels containing a cross-linked hyaluronic acid (HA) network and investigated their antioxidant activities.Methods : In the first step, we made poly hydroxyethyl methacrylate(p(HEMA))-based hydrogels post-modified with an interpenetrating polymer network(IPN) structure composed of HA polymers and a p(HEMA) network. The subsequent functionalization with dopamine via an amide coupling reaction resulted in the antioxidant hydrogels. Their antioxidant activities were evaluated using 2,2’-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assays.Results : The dopamine-modified hydrogels exhibited significant antioxidant activities, when compared to unmodified control. The presence of the HA–IPN structure improved the surface wettability of the hydrogel while dopamine-conjugated IPN hydrogel did not demonstrate the significant difference compared to hydrogel control. Dopamine-modified hydrogels exhibited high transmittance (>88%).Conclusion : The results demonstrate that the development of antioxidant hydrogels based on dopamine-conjugated HA–IPN structures may help develop ophthalmic and biomedical materials.

Conductive and Tough Hydrogels Based on Biopolymer Molecular Templates for Controlling in Situ Formation of Polypyrrole Nanorods.

Conductive hydrogels (CHs) have gained significant attention for their wide applications in biomedical engineering owing to their structural similarity to soft tissues. However, designing CHs that combine biocompatibility with good mechanical and electrical properties is still challenging. Herein, we report a new strategy for the fabrication of tough CHs with excellent conductivity, superior mechanical properties, and good biocompatibility by using chitosan framework as molecular templates for controlling conducting polypyrrole (PPy) nanorods in situ formation inside the hydrogel networks. First, polyacrylamide/chitosan (CS) interpenetrating polymer network hydrogel was synthesized by UV photopolymerization; second, hydrophobic and conductive pyrrole monomers were absorbed and fixed on CS molecular templates and then polymerized with FeCl3 in situ inner hydrophilic hydrogel network. This strategy ensured that the hydrophobic PPy nanorods were uniformly distributed and integrated with the hydrophilic polymer phase to form highly interconnected conductive path in the hydrogel, endowing the hydrogel with high conductivity (0.3 S/m). The CHs exhibited remarkable mechanical properties after the chelation of CS by Fe3+ and the formation of composites with the PPy nanorods (fracture energy 12 000 J m-2 and compression modulus 136.3 MPa). The use of a biopolymer molecular template to induce the formation of PPy nanostructures is an efficient strategy to achieve conductive multifunctional hydrogels.

Synthesis of interpenetrating network hydrogel from (gum copal alcohols-collagen)-co-poly(acrylamide) and acrylic acid: Isotherms and kinetics study for removal of methylene blue dye from aqueous solution

A novel interpenetrating polymeric network (IPN) [(GcA-coll)-cl-poly (AAm-ip-AA)] hydrogel has been synthesized by free radical polymerization of (gum copal alcohols-collagen) backbone using potassium persulphate (KPS) as initiator, N,N′-methylene-bis-acrylamide (MBA) as crosslinker, acrylamide (AAm) as primary monomer and acrylic acid (AA) as secondary monomer. Isotherms and kinetics of dye adsorption by the IPN were also studied. The optimum conditions for the removal of methylene blue dye with the maximum adsorption capacity of 1.70 mg/g from aqueous solution are pH ∼7, initial dye concentration = 12 ppm, adsorbent dose = 300 mg. The adsorbent also exhibited excellent regeneration efficiency for the three successive adsorption-desorption cycles. The Gum Copal and Collagen based IPN hydrogel was found to be a cost effective and renewable potential candidate with excellent regeneration efficiency to be used as an adsorbent for the removal of methylene blue from the aqueous solutions.

Thermosensitive Behavior and Super-Antibacterial Properties of Cotton Fabrics Modified with a Sercin-NIPAAm-AgNPs Interpenetrating Polymer Network Hydrogel.

Poly(N-isopropylacrylamide) (PNIPAAm), sericin (SS), and silver nitrate were combined to prepare an interpenetrating network (IPN) hydrogel having dual functions of temperature sensitivity and antibacterial properties. The structure and size of AgNPs in such an IPN hydrogel were characterized by the Fourier Transform Infrared spectrum (FT-IR), X-ray powder diffraction (XRD) and Transmission Electron Microscope (TEM), and the thermal properties of the IPN hydrogel were characterized by Differential Scanning Calorimetry (DSC). Based on XRD patterns, Ag+ was successfully reduced to Ag0 by SS. It was observed by TEM that the particle size of silver particles was lower than 100 nm. The glass transition temperature (Tg) of IPN hydrogel was better than that of the PNIPAAm/AgNPs hydrogels, and lower critical solution temperature (LCST) values of the IPN hydrogel were obtained by DSC i.e. 31 °C. The thermal stability of the IPN hydrogel was successfully determined by the TGA. This IPN hydrogel was then used to modify the cotton fabrics by the “impregnation” method using glutaraldehyde (GA) as the cross-linking agent. The structures and properties of IPN hydrogel modified cotton fabric were characterized by scanning electron microscopy (SEM), FT-IR, and the thermogravimetry analysis (TGA). The results show that NIPAAm was successfully polymerized into PNIPAAm, and that there were neglected new groups in the hydrogel IPN. The IPN hydrogel was then successfully grafted onto cotton fabrics. SEM observations showed that the IPN hydrogel formed a membrane structure between the fibers, and improved the compactness of the fibers. At the temperature close to LCST (≈31 °C), the entire system was easily able to absorb water molecules. However, the hydrophilicity tended to decrease when the temperature was higher or lower than the LCST. The antibacterial rates of the modified cotton fabric against S. aureus and E. coli were as high as 99%.

Composite Cellularized Structures Created from an Interpenetrating Polymer Network Hydrogel Reinforced by a 3D Woven Scaffold.

Biomaterial scaffolds play multiple roles in cartilage tissue engineering, including controlling architecture of newly formed tissue while facilitating growth of embedded cells and simultaneously providing functional properties to withstand the mechanical environment within the native joint. In particular, hydrogels-with high water content and desirable transport properties-while highly conducive to chondrogenesis, often lack functional mechanical properties. In this regard, interpenetrating polymer network (IPN) hydrogels can provide mechanical toughness greatly exceeding that of individual components; however, many IPN materials are not biocompatible for cell encapsulation. In this study, an agarose and poly(ethylene) glycol IPN hydrogel is seeded with human mesenchymal stem cells (MSCs). Results show high viability of MSCs within the IPN hydrogel, with improved mechanical properties compared to constructs comprised of individual components. These properties are further strengthened by integrating the hydrogel with a 3D woven structure. The resulting fiber-reinforced hydrogels display functional macroscopic mechanical properties mimicking those of native articular cartilage, while providing a local microenvironment that supports cellular viability and function. These findings suggest that a fiber-reinforced IPN hydrogel can support stem cell chondrogenesis while allowing for significantly enhanced, complex mechanical properties at multiple scales as compared to individual hydrogel or fiber components.

Biodegradable IPN Hydrogels Based on Pre-vulcanized Natural Rubber and Cassava Starch as Coating Membrane for Environment-Friendly Slow-Release Urea Fertilizer

Biodegradable interpenetrating polymer network (IPN) hydrogels based on pre-vulcanized natural rubber (NR) and cassava starch (St) using sulphur (S) and glutaraldehyde (GA) as crosslinkers were developed in a solution form as a coating membrane for slow-release nitrogen fertilizer. The NR/St ratios affecting water swelling, water permeability and biodegradation were investigated. Results revealed that water swelling, water permeability and biodegradation of IPN NR/St hydrogels decreased with increasing NR content. The wax was used as outer coating shell to further improve the release characteristic of the coated urea. The urea bead (UB) coated with IPN NR/St and wax layers (W-IPN-CUB) exhibited exceptional release behavior up to 24 days in soil compared to native UB (3 days). The release mechanisms of W-IPN-CUB in both water and soil environments were a non-Fickian diffusion with n = 0.88 and 0.85, respectively, relating to the diffusion through porous membrane. Also, the W-IPN-CUB was able to slow the leaching of urea fertilizer and significantly improve the performances of corn and basil height compared to native UB (P < 0.05). Thus, the W-IPN-CUB material proved to be a good candidate material for slow release fertilizer which could be widely used in agricultural and horticultural applications.

Interpenetrating polymer network hydrogels composed of chitosan and photocrosslinkable gelatin with enhanced mechanical properties for tissue engineering

Gelatin and chitosan (CS) are widely used natural biomaterials for tissue engineering scaffolds, but the poor mechanical properties of pure gelatin or CS hydrogels become a big obstacle that limits their use as scaffolds, especially in load-bearing tissues. This study provided a novel mechanism of forming interpenetrating network (IPN) of gelatin methacryloyl (GelMA) and CS hydrogels by covalent bonds and hydrophobic interactions through photocrosslinking and basification, respectively. By characterization of the compressive and tensile moduli, ultimate tensile stress and strain, it was found that semi-IPN and IPN structure can greatly enhance the mechanical properties of GelMA-CS hydrogels compared to the single network CS or GelMA. Moreover, the increase of either GelMA or CS concentration can strengthen the hydrogel network. Then, the swelling, enzymatic degradation, and morphology of GelMA-CS hydrogels were also systematically investigated. The excellent biocompatibility of GelMA-CS hydrogels was demonstrated by large spreading area of bone mesenchymal stem cells on hydrogel surfaces when CS concentration was <2% (w/v). According to this study, the multiple requirements of properties can be fulfilled by carefully selecting the GelMA and CS compositions for IPN hydrogels.

Properties and in vitro drug release of pH- and temperature-sensitive double cross-linked interpenetrating polymer network hydrogels based on hyaluronic acid/poly (N-isopropylacrylamide) for transdermal delivery of luteolin

In this study, we prepared double cross-linked interpenetrating polymer network (IPN) hydrogels composed of temperature sensitive poly (N-isopropylacrylamide) (PNIPAM) and pH sensitive hyaluronic acid (HA) by radical polymerization and Michael addition. Their physicochemical properties for transdermal delivery of luteolin inhibiting the hyperproliferation of keratinocytes in psoriasis were investigated and drug release studies were performed. Double networks of HA/PNIPAM IPN hydrogel were identified through FT-IR and 13CNMR. By measuring the swelling ratios pH and temperature sensitivity were confirmed, and it was influenced by the content of a cross-linking agent. As a result of texture analysis and rheometry, a IPN hydrogel with 3% crosslinker content had the most adhesive and stable cross-linked network. Therefore, luteolin was loaded on this hydrogel. Its drug release behavior was determined at various temperatures and pH using several drug release kinetic models. As a result of skin permeation study, HA/PNIPAM IPN hydrogel effectively delivers luteolin to the epidermis and dermis. No toxicity was observed as a result of observing cytotoxicity of the hydrogel for application to the skin. In conclusion, IPN hydrogels can be developed as carriers of transdermal delivery system of luteolin for psoriasis skin relief.

Dual-responsive IPN hydrogel based on sugarcane bagasse cellulose as drug carrier

In this work, the stepwise synthesis of interpenetrating polymer network (IPN) strategy was developed in an attempt to fabricate novel hydrogels consisting of sugarcane bagasse cellulose (SBC), carboxymethylcellulose (CMC) and poly (N-isopropylacrylamide) (PNIPAm) as a dual-responsive drug carrier. The pretreated and dissolved SBC was pre-crosslinked using epichlorohydrin in the presence of CMC, followed by in-situ free-radical polymerization of NIPAm in the presence of N,N′-Methylene-bis(acrylamide) as a crosslinking agent. The carboxyl groups in CMC and PNIPAm chains rendered the resulting hydrogel pH and thermal responsive. The results from scanning electron microscopy, infrared spectroscopy, thermogravimetric analysis and mechanical property testing demonstrated the successful formation of the IPN with proper structure and mechanical strength. The swelling experiments at different temperatures and pH showed the dual–sensibility of the hydrogels. Moreover, bovine serum albumin (BSA) was used as a model drug and loaded in the hydrogel; and the drug release behavior was revealed in phosphate buffer solution (PBS) and simulated gastric fluid (SGF). The results indicated that the dual-responsive IPN hydrogel is of great potential for the controlled release of drug.

Dynamic properties of hydrogels and fiber-reinforced hydrogels.

Hydrophilic polymers, or hydrogels, are used for a wide variety of biomedical applications, due to their inherent ability to withhold a high-water content. In recent years, a large effort has been focused on tailoring the mechanical properties of these hydrogels to become more appropriate materials for use as anatomical and physiological structural supports. A few of these such methods include using diverse types of polymers, both natural and synthetic, varying the type of molecular cross-linking, as well as combining these efforts to form interpenetrating polymer network hydrogels. While multiple research groups have characterized these various hydrogels under quasi-static conditions, their dynamic properties, representative of native physiological loading scenarios, have been scarcely reported. In this study, an E-glass fiber reinforced family of alginate/PAAm hydrogels cross-linked by both divalent and trivalent cations are fabricated and investigated. The effect of the reinforcement phase on the dynamic and hydration behaviors is then explicated. Additionally, a micromechanics framework for short cylindrical chopped fibers is utilized to discern the contribution of the matrix and fiber constituents on the hydrogel composite. The addition of E-glass fibers resulted in the storage modulus exhibiting a ~50%, 5%, and ~120%, increase with a mere addition of 2 wt% of the reinforcing fibers to Na-, Sr-, and Al-alginate/PAAm, respectively. In studying the cross-linking effect of various divalent (Ba, Ca, Sr) and trivalent (Al, Fe) cations, it was noteworthy that the hydrogels were found to be effective in dissipating energy while resisting mechanical deformation when they are cross-linked with higher molecular weight elements, regardless of valency. This report on the dynamic properties of these hydrogels will help to improve their optimization for future use in biomedical load-bearing applications.

Interpenetrating networks hydrogels based on hyaluronic acid for drug delivery and tissue engineering

ABSTRACTThere are several techniques for preparing hydrogel biomaterials. Among these techniques, preparation of interpenetrating polymer networks hydrogel (IPNs) has been more interested during last years. IPNs are fabricated by the incorporation of monomers or polymeric chains in hydrogel network. Natural polymers such as hyaluronic acids have some advantages such as biocompatibility, biodegradability and non-toxicity. In this review, we would have a brief view to the interpenetrating polymer networks hydrogel based on hyaluronic acids and its applications as a drug delivery system and tissue engineering applications.

Synthesis and RSM‐CCD optimization of microwave‐induced green interpenetrating network hydrogel adsorbent based on gum copal for selective removal of malachite green from waste water

In the recent study, microwave induced novel interpenetrating polymeric network (IPN) hydrogel based on gum copal‐collagen (GcA‐coll) has been reported for the efficient removal of malachite green dye from the waste water. The IPN [(GcA‐coll)‐cl‐poly (AAm‐ip‐AA)] was synthesized using potassium persulfate (KPS)—N,N′‐methylene‐bis‐acrylamide (MBA) as initiator‐ crosslinker system, acrylamide (AAm) as primary monomer and acrylic acid (AA) as secondary monomer under microwave radiations. The Response Surface Methodology (RSM) design was used to optimize the percentage swelling of the candidate IPN hydrogel. RSM based Central Composite Design (CCD) was applied to the three most crucial synthesis parameters like initiator concentration, monomer concentration and crosslinker concentration so as to maximize the percentage swelling. The optimum conditions for the removal of 88% malachite green dye from waste water are pH ∼ 7, initial dye concentration = 12 mg mL−1, adsorbent dose = 500 mg. Pseudo first order and Pseudo‐second order models were applied to study the kinetics and the mechanism of adsorption was studied by intraparticle diffusion model. The equilibrium data was further evaluated by Langmuir and Freundlich isotherm models. The synthesized IPN was found to be a propitious candidate to be used as a green adsorbent for removing malachite green dye from waste water. POLYM. ENG. SCI., 58:2293–2303, 2018. © 2018 Society of Plastics Engineers

New Multichannel Frontal Polymerization Strategy for Scaled-up Production of Robust Hydrogels

Herein, we report a new facile and safe pathway for the scaled-up production of mechanically strong and multiresponsive interpenetrating polymer network (IPN) hydrogels via multichannel frontal polymerization (multichannel FP). We designed a two-part system, of which part-1 contained high reactive monomer and could polymerize spontaneously. The polymerization of part-1 released tremendous amount of heat, subsequently initiating FP of part-2 to convert monomers to polymers without any external energy, which is flexible, cost-effective, and environmental. Multichannel FP not only allowed realization of parallel polymerization to obtain a number of hydrogels but also solved center overheating and explosion problem stemmed from a large reaction vessel. Compared with the sample prepared in bigger tubular reactor, product synthesized via multichannel FP showed more excellent thermal stability, morphology and mechanical properties. Moreover, the as-prepared IPN hydrogels exhibited chemical-, pH-, and thermal-sen...

Influence of Ethylene Glycol Methacrylate to the Hydration and Transition Behaviors of Thermo-Responsive Interpenetrating Polymeric Network Hydrogels.

The influence of ethylene glycol methacrylate (EGMA) to the hydration and transition behaviors of thermo-responsive interpenetrating polymeric network (IPN) hydrogels containing sodium alginate, N-isopropylacrylamide (NIPAAm), and EGMA were investigated. The molar ratios of NIPAAm and EGMA were varied from 20:0 to 19.5:0.5 and 18.5:1.5 in the thermo-responsive alginate-Ca2+/P(NIPAAm-co-EGMA) IPN hydrogels. Due to the more hydrophilicity and high flexibility of EGMA, the IPN hydrogels exhibited higher lower critical solution temperature (LCST) and lower glass transition temperature (Tg) when the ratio of EGMA increases. The swelling/deswelling kinetics of the IPN hydrogels could be controlled by adjusting the NIPAAm/EGMA molar ratio. A faster water uptake rate and a slower water loss rate could be realized by increase the amount of EGMA in the IPN hydrogel (the shrinking rate constant was decreased from 0.01207 to 0.01195 and 0.01055 with the changing of NIPAAm/EGMA ratio from 20:0, 19.5:0.5 to 18.5:1.5). By using 2-Isopropylthioxanthone (ITX) as a photo initiator, the obtained alginate-Ca2+/P(NIPAAm-co-EGMA360) IPN hydrogels were successfully immobilized on cotton fabrics. The surface and cross section of the hydrogel were probed by scanning electron microscopy (SEM). They all exhibited a porous structure, and the pore size was increased with the amount of EGMA. Moreover, the LCST values of the fabric-grafted hydrogels were close to those of the pure IPN hydrogels. Their thermal sensitivity remained unchanged. The cotton fabrics grafted with hydrogel turned out to be much softer with the continuous increase of EGMA amount. Therefore, compared with alginate-Ca2+/PNIPAAm hydrogel, alginate-Ca2+/P(NIPAAm-co-EGMA360) hydrogel is a more promising candidate for wound dressing in the field of biomedical textile.

A Novel Design Strategy for Temperature-Responsive IPN Hydrogels Based on a Copolymer of Acrylamide and N-(1,1-Dimethyl-3-Oxobutyl)-Acrylamide

A methology is described for the synthesis of novel temperature-responsive interpenetrating polymer network (IPN) hydrogels with poly(2-acrylamido- 2-methylpropane sulfonic acid) (PAMPS) as a tightly crosslinked 1st network, temperature-responsive poly(acrylamide-co-N-(1,1-dimethyl-3-oxobutyl)- acrylamide) (P(AM-co-DAAM)) with low cost as a lossely crosslinked 2nd network. The structure and morphology of the IPN hydrogels were characterized by FTIR, TGA and SEM, and the results indicated that PAMPS network introduced P(AM-co-DAAM) hydrogels have large, thermally stable and interconnected porous network. The properties of the IPN hydrogels, which include: swelling capacity, equilibrium swelling/deswelling ratio, temperature- responsive behavior, and the dwelling kinetics as specific temperature, were investigated carefully. Results showed that the obtained IPN hydrogels displayed a controllable equilibrium swelling/deswelling behavior and possessed remarkable thermosensitivity. In addition, the results also indicate that the incorporation of the hydrophobic groups DAAM has a big effect on the LCST of the IPN hydrogels. Consequently, these novel temperature-responsive IPN hydrogels with low cost and slow-releasing performance would be promising for potential applications, such as environmental catalysis, water treatment, and agriculture.

Co-delivery of deferoxamine and hydroxysafflor yellow A to accelerate diabetic wound healing via enhanced angiogenesis

Nonhealing chronic wounds on foot induced by diabetes is a complicated pathologic process. They are mainly caused by impaired neovascularization, neuropathy, and excessive inflammation. A strategy, which can accelerate the vessel network formation as well as inhibit inflammatory response at the same time, makes it possible for effective diabetic ulcers treatment. Co-delivery of multiple drugs with complementary bioactivity offers a strategy to properly treat diabetic wound. We previously demonstrated that hydroxysafflor yellow A (HSYA) could accelerate diabetic wound healing through promoting angiogenesis and reducing inflammatory response. In order to further enhance blood vessel formation, a pro-angiogenic molecular called deferoxamine (DFO) was topically co-administrated with HSYA. The in vitro results showed that the combination of DFO and HSYA exerted synergistic effect on enhancing angiogenesis by upregulation of hypoxia inducible factor-1 alpha (HIF-1α) expression. The interpenetrating polymer networks hydrogels, characterized by good breathability and water absorption, were designed for co-loading of DFO and HSYA aiming to recruit angiogenesis relative cells and upgrade wound healing in vivo. Both DFO and HSYA in hydrogel have achieved sustained release. The in vivo studies indicated that HSYA/DFO hydrogel could accelerate diabetic wound healing. With a high expression of Hif-1α which is similar to that of normal tissue. The noninvasive US/PA imaging revealed that the wound could be recovered completely with abundant blood perfusion in dermis after given HSYA/DFO hydrogel for 28 days. In conclusion, combination of pro-angiogenic small molecule DFO and HSYA in hydrogel provides a promising strategy to productively promote diabetic wound healing as well as better the repair quality.