Preformed Hydrogel Research Articles

Weak Bond-Based Injectable and Stimuli Responsive Hydrogels for Biomedical Applications.

Here we define hydrogels crosslinked by weak bonds as physical hydrogels. They possess unique features including reversible bonding, shear thinning and stimuli-responsiveness. Unlike covalently crosslinked hydrogels, physical hydrogels do not require triggers to initiate chemical reactions for in situ gelation. The drug can be fully loaded in a pre-formed hydrogel for delivery with minimal cargo leakage during injection. These benefits make physical hydrogels useful as delivery vehicles for applications in biomedical engineering. This review focuses on recent advances of physical hydrogels crosslinked by weak bonds: hydrogen bonds, ionic interactions, host-guest chemistry, hydrophobic interactions, coordination bonds and π-π stacking interactions. Understanding the principles and the state of the art of gels with these dynamic bonds may give rise to breakthroughs in many biomedical research areas including drug delivery and tissue engineering.

Mitigating permeability contrasts in heterogenous reservoirs using advanced preformed particle gels

The present work presents a nanocomposite preformed particle gel for conformance control in mature oilfields. This product was observed to have a better performance than conventional hydrogels without nanomaterials. Preformed particle hydrogel was designed by the reaction of monomer, initiator, cross-linker, additives, and sodium montmorillonite nanomaterial, whereas conventional hydrogel is designed from just monomer, initiator, cross-linker and additives. The presence of nanomaterial in hydrogel design affords it tremendous improvement in nanocomposite gel properties and behaviour compared to conventional hydrogels without any nanomaterial. Additionally, swelling performance, post-degraded gel viscosity, and long-term thermal resistance of nanocomposite gel increased by several orders of magnitude compared to hydrogels with no nanomaterial. Environmental scanning electron microscopy (ESEM) revealed the presence of a very dense 3D network compared to hydrogels with no nanomaterial. On incorporation of nanomaterial, increase in gel strength of up to 600% was observed. Thus, they are potential replacements for existing preformed particle gels in mitigating permeability variations in mature reservoirs. [Received: March 14, 2014; Accepted: March 2, 2015]

Glycosaminoglycan - biohybrid hydrogels for the immune modulation in wound healing

Event Abstract Back to Event Glycosaminoglycan - biohybrid hydrogels for the immune modulation in wound healing Lucas Schirmer1, Uwe Freudenberg1 and Carsten Werner1, 2 1 Leibniz-Institut für Polymerforschung Dresden, Max Bergmann Center of Biomaterials, Germany 2 Technische Universität Dresden, Center for Regenerative Therapies Dresden (CRTD), Germany Introduction: Chronic wounds represent a challenge for conventional wound treatment. The underlying dysregulation of inflammatory signals can lead to a severe impairment of the tissue regeneration. In this pathogenic state, the inflammatory phase of wound healing is prolonged due to the massive production of inflammatory cytokines in the surrounding tissue. To address these severe problem, novel materials for the targeted treatment of severely inflamed wounds are urgently needed. Therefore we developed a modular starPEG-glycosaminoglycan (GAG) hydrogel[1], that efficiently administrate the anti-inflammatory interleukins 4 and 10. The high GAG content of the matrix in particular is the key for the protection and sustained release of both cytokines, which are crucial for the resolvement of inflammation and the support of regenerative processes during wound healing[2],[3]. In here, we show the ability of the versatile IL4 and 10 releasing hydrogel matrix to decrease the inflammatory response of immune cells and to induce their regenerative polarization. Materials and Methods: Well defined hydrogels were formed through Michael addition crosslinking of a four-arm poly(ethylene glycol) and the GAG heparin while IL4 and IL10 were non-covalently conjugated through electrostatic interaction to the heparin (Fig. 1 A/B). The release of both interleukins was characterized in medium supplemented with 0.1% BSA utilizing ELISA-techniques. Consequently, the effects of IL4- and IL10-loaded hydrogels were tested on primary macrophages challenged with bacterial LPS. The amount of inflammatory factors released were measured by multiplex analysis and the gene expression was analyzed by rt-PCR. Finally, the materials were tested in vivo by implanting preformed hydrogel discs in 4 mm back skin wounds of 8 week old mice. Results and Discussion: The starPEG GAG hydrogel platform showed a tunable and sustained release over at least 168h (Fig. 1 B). Furthermore, the released amount of both cytokines could be independently adjusted through the variation of the initial loading concentration. IL10 functionalized hydrogels effectively suppressed the inflammatory response of macrophages in vitro (Fig. 2 A). While the IL-4 loaded materials did not influence the amount of inflammatory factors released, they induced the regenerative response of macrophages indicated by the marker genes Arg1 and Ym1 (Fig.2 B). Moreover, IL4-loaded hydrogels induced collagen I/III deposition of primary dermal fibroblasts. Interestingly, the application of hydrogels functionalized with a combination of IL4 and IL10 result in the decrease of the inflammatory response as well as the increase of pro-regenerative behavior of macrophages. In line with this, we found a decreased invasion of immune cells to the wound if the hydrogels were transplanted in a murine model. Conclusion: The starPEG-GAG hydrogels can be utilized for the sustained release of multiple anti-inflammatory cytokines for relevant time periods. They effectively decrease the inflammatory response and promote the regenerative behavior in macrophages and fibroblast, two cell types essential in the control of wound healing. In essence, the in here introduced IL4- and IL10-functionalized biohybrid hydrogels are very promising as novel wound dressings capable for the regulation of chronically inflamed wounds. This work was supported by the Deutsche Forschungsgemeinschaft (SFB-TR67).

Degradable nanocomposite preformed particle gel for chemical enhanced oil recovery applications

Abstract In this work, we present a preformed particle hydrogel with a more superior performance than conventional hydrogels with potential conformance control applications in mature oilfields. Preformed particle hydrogel was designed by the reaction of monomer, initiator, crosslinker, additives, and laponite XLG nanoclay, whereas conventional hydrogel is designed from just monomer, initiator, crosslinker and additives. The presence of nanomaterial in hydrogel design affords it tremendous improvement in nanocomposite gel properties and behavior compared to conventional hydrogels without any nanomaterial. On incorporation of nanomaterial, increase in gel strength of up to 394% was observed. Additionally, swelling performance, post-degraded gel viscosity, and long-term thermal resistance of nanocomposite gel increased by several orders of magnitude compared to hydrogels with no nanomaterial. Environmental Scanning Electron Microscopy (ESEM) revealed the presence of a very dense 3-D network compared to hydrogels with no nanomaterial. It was observed that after degradation, nanocomposite hydrogel had a post-degradation viscosity of 4437 cp whereas hydrogel with no nanomaterial had a post-degradation viscosity of 170 cp. Thus, degradable laponite XLG nanocomposite hydrogels are recommended for secondary polymer flooding, since they have a high post-degradation viscosity under anaerobic conditions.

A more superior preformed particle gel with potential application for conformance control in mature oilfields

The present work presents a nanocomposite preformed particle gel for conformance control in mature oilfields. This product was observed to have a better performance than conventional hydrogels without nanomaterials. Preformed particle hydrogel was designed by the reaction of monomer, initiator, crosslinker, additives, and calcium montmorillonite nanomaterial, whereas conventional hydrogel is designed from just monomer, initiator, crosslinker and additives. The presence of nanomaterial in hydrogel design affords it tremendous improvement in nanocomposite gel properties and behavior compared to conventional hydrogels without any nanomaterial. Additionally, swelling performance, post-degraded gel viscosity, and long-term thermal resistance of nanocomposite gel increased by several orders of magnitude compared to hydrogels with no nanomaterial. Environmental Scanning Electron Microscopy (ESEM) revealed the presence of a very dense 3-D network compared to hydrogels with no nanomaterial. On incorporation of nanomaterial, increase in gel strength of up to 2,150 % was observed. Thus, they are potential replacements for existing preformed particle gels in mitigating permeability variations in mature reservoirs.

The Evaluation of Two New Hyaluronan Hydrogels as Nasal Dressing in the Rabbit Maxillary Sinus

The postoperative scaring, ostial stenosis, and adhesions after functional endoscopic sinus surgery for chronic rhinosinusitis remains a major problem. This study was designed to evaluate two new hyaluronan (HA) hydrogels for neo-ostium antistenosis and promoting wound healing in a rabbit maxillary sinus model. The anterior wall of the maxillary sinus of 48 rabbits was removed to create a 4-mm circumferential wound both on the nasal and on the sinus sides. A rapid-gelling HA hydrogel or preformed HA hydrogel was filled randomly into the right or left sinus, while the opposite sinus served as blank control or was treated with Merogel (Medtronic Xomed Surgical Products, Jacksonville, FL) as control. The neo-ostium diameter and histological scores were evaluated and analyzed postoperatively. The neo-ostium diameter in the rapid-gelling HA hydrogel-treated side was significantly larger than that in the blank control side with a mean difference of 1.46 ± 0.99 mm (p = 0.03), 1.30 ± 0.61 mm (p = 0.0087), and 1.60 ± 0.25 mm (p = 0.00015) at 2, 3, and 4 weeks, respectively; the neo-ostium diameter in the preformed HA hydrogel-treated side at 2 weeks was significantly larger than that in the blank control side or Merogel control side with a mean difference of 1.46 ± 0.76 mm (p = 0.002) or 0.54 ± 0.36 mm (p = 0.007), respectively. The preformed HA hydrogel-treated side showed better histology scores at 2 weeks in heterophils, fibrosis, and osteogenesis than the blank control, and the chronic inflammation (lymphocyte/plasmacyte infiltration) was not prevalent. During the postoperative follow-up period both of the two HA hydrogels significantly prevented neo-ostium stenosis and the preformed HA hydrogel promoted wound healing.

Polysaccharide based covalently linked multi-membrane hydrogels

Layer-by-layer techniques bear great potential for biomaterials as they allow sequential construction of hierarchical constructs. This especially accounts for hydrogels which can be tuned for biochemically, morphologically and mechanically different microenvironments and find numerous applications for encapsulation and release of drugs and cells. Here we present a novel radiation-free preparation method for multi-membrane hydrogels based on polysaccharides using prepolymer cross-linkers. Isocyanate functional prepolymers were used either alone or for cross-linking unmodified hyaluronic acid to form hydrolytically stable hydrogel membranes, whereas acrylate-bearing prepolymers were used to cross-link thiofunctional hyaluronic acid resulting in fully degradable hydrogel layers. Covalently linked multi-membrane systems can be formed through initial formation of a central hydrogel core followed by sequential embedding of the preformed hydrogel in an aqueous precursor solution for the following membrane. As a proof of principle, sequential drug release from a three layer system is shown in which ampicillin and dexamethasone were embedded in the outer and inner membranes, respectively, with a hydrolytically stable middle membrane as separation layer and diffusion barrier.

Patterning hydrogels in three dimensions towards controlling cellular interactions

The 3-dimensional (3D) interaction between cells and extracellular matrix (ECM) constitutes a dynamic regulatory system for directing tissue formation and homeostasis, as well as regeneration in response to injury. As such, significant progress has been made in the field of tissue engineering to develop 3D hydrogels capable of promoting cell viability and many of these important ECM interactions. However, the spatial patterning of hydrogels in 3D, motivated by the microscale heterogeneity of native tissue architectures, has only recently been a focus. Here, we review efforts to date to engineer structurally and/or biochemically patterned 3D hydrogels to control cellular behavior for regenerative medicine applications. Such techniques can be separated into two categories: stereolithographic “bottom-up” methods that pattern structures during layer-by-layer fabrication and post-gelation techniques involving modification of a uniform, pre-formed hydrogel. Many techniques in each group are further compatible with cell encapsulation, providing a valuable set of models for studying cell-cell signaling or for the engineering of new tissues.

Structure and Properties of Urea‐Crosslinked Star Poly[(ethylene oxide)‐ran‐(propylene oxide)] Hydrogels

Isocyanate-terminated six armed star shaped macromers with a statistical copolymer backbone consisting of 80% EO and 20% PO have previously demonstrated excellent protein and cell repellence as nano-layered surfaces. In this study, various macromers are mixed with water and provide a spectrum of materials that range from particles to uniform hydrogels. Due to hydrophobic end groups, 3 kDa molecular weight macromers result in micro and nano-particles, while 18 kDa macromers completely dissolve and consequently uniform, transparent, high water content hydrogels are formed. Oriented channels may be induced into these hydrogels through the controlled freezing of water in the preformed hydrogel.

Hydrogel-Templated Growth of Large Gold Nanoparticles: Synthesis of Thermally Responsive Hydrogel−Nanoparticle Composites

In this paper, we describe a unique strategy for preparing discrete composite nanoparticles consisting of a large gold core (60-150 nm in diameter) surrounded by a thermally responsive nontoxic hydrogel polymer derived from the polymerization of N-isopropylacrylamide (NIPAM) or a mixture of NIPAM and acrylic acid. We synthesize these composite nanoparticles at room temperature by inducing the growth of gold nanoparticles in the presence of preformed spherical hydrogel particles. This new method allows precise control of the size of the encapsulated gold cores (tunable between 60 and 150 nm) and affords composite nanoparticles possessing diameters ranging from as small as 200 nm to as large as 550 nm. Variable-temperature studies show that the hydrodynamic diameter of these composite nanoparticles shrinks dramatically when the temperature is increased above the lower critical solution temperature (LCST); correspondingly, when the temperature is lowered below the LCST, the hydrodynamic diameter expands to its original size. These composite nanoparticles are being targeted for use as optically modulated drug-delivery vehicles that undergo volume changes upon exposure to light absorbed by the gold nanoparticle core.

Reduced postoperative intra-abdominal adhesions using Carbylan-SX, a semisynthetic glycosaminoglycan hydrogel

To compare the efficacy of crosslinked Carbylan-SX (Carbylan BioSurgery, Inc., Palo Alto, CA) hydrogel films and sprayable gels as physical barriers in reducing postoperative intra-abdominal adhesions in the rat cecum-abdominal wall and rat uterine horn models. Pre-formed crosslinked Carbylan-SX films and sprayable in situ crosslinkable Carbylan-SX gels were evaluated in rat cecum-abdominal wall and rat uterine horn models and compared with commercially available and clinically used Seprafilm. University animal research facility. Female Wistar rats. Abrasions were made with the foot-pedal-operated Flex-shaft (Dremel, Racine, WI) on both the cecum and abdominal wall (each area 10 mm in diameter) in female rats as one model and on both uterine horns (3 x 10 mm) in female rats as the other model. In each of the two adhesion models, four groups were assigned with eight rats in each group: (1) untreated control, (2) treated with Seprafilm (Genzyme Corporation, Cambridge, MA), (3) treated with preformed Carbylan-SX hydrogel films, and (4) treated with sprayable Carbylan-SX gel. Extent and severity of postoperative adhesions between the cecum and the abdominal wall in rat cecum-abdominal wall model and between the uterine horns in rat uterine horn model. The Carbylan-SX film and the Carbylan-SX sprayable gel led to fewer adhesions than Seprafilm in both rat adhesion models. Interestingly, a single physical form was not optimal for both models: the Carbylan film was more efficacious in the rat uterine horn model, whereas Carbylan gel gave the best results in the rat cecum-abdominal wall model. Both Carbylan-SX film and gel were efficacious in reducing postoperative intra-abdominal adhesion formation in rat cecum-abdominal wall and uterine horn models.

Polypyrrole-hydrogel composites for the construction of clinically important biosensors

The present study reports on the use of p(2-hydroxyethyl methacrylate) (pHEMA) in which polypyrrole and various oxidoreductase enzymes were physically entrapped to function as a viable matrix for the construction of clinically important amperometric biosensors. Glucose oxidase, cholesterol oxidase and galactose oxidase biosensors were constructed. Electrode-supported hydrogel films were prepared by UV polymerization of the HEMA component (containing the dissolved enzyme) followed immediately by electrochemical polymerization (+0.7V vs. Ag/AgCl) of the pyrrole component within the interstitial spaces of the pre-formed hydrogel network. The optimized glucose oxidase biosensor displayed a wide linear glucose response range (5.0×10 −5 to 2.0×10 −2 M), a detection limit (3S y/ x /sensitivity) of 25 μM and a response time of 35–40 s. The analytical recovery of glucose in serum samples ranged from 98 to 102% with mean coefficients of variation of 4.4% (within-day analyses) and 5.1% (day-to-day analyses). All three sensors displayed good stabilities when stored desiccated in the absence of buffer (>9 months).

COMPOSITE HYDROGELS CONTAINING POLYPYRROLE AS SUPPORT MEMBRANES FOR AMPEROMETRIC ENZYME BIOSENSORS

Conducting polymers and redox hydrogels are shown to be attractive materials for biocompatible electrodes in amperometric biosensors. We have combined electrically conducting polypyrrole (PPy) with crosslinked poly(2-hydroxyethylmethacrylate) (p-HEMA) to produce a novel composite hydrogel membrane. The high water content of these materials provides a biocompatible environment for the long-term immobilization of enzymes and a more favorable medium for the rapid movement of charge neutralizing ions. Electrode-supported composite films were prepared by UV polymerization of the hydrogel component (containing dissolved enzyme) followed immediately by electrochemical polymerization (+0.7V vs. Ag/AgCl) of the pyrrole component within the interstitial spaces of the pre-formed hydrogel network. Typical monomer compositions consisted of HEMA:TEGDA:pyrrole in an 85:10:05 vol%. (TEGDA = tetraethyleneglycol diacrylate). An optimized glucose biosensor displayed a wide linear response range of 5.0 × 10−5 to 2.0 × 10−2 M, a detection limit (3Sy/x/sensitivity) of 25 μM and a response time of 35–40 seconds. The analytical recovery of glucose in serum samples ranged from 98 to 102% with mean coefficients of variation of 4.4% (within-day analyses) and 5.1% (day-to-day analyses). The optimized cholesterol and galactose biosensors also displayed wide linear response ranges (5.0 × 10−4 – 1.5 × 10−2M and 1.0 × 10−4 – 1.0 × 10−2M, respectively) towards their respective substrates. All three biosensors retained > 70% of initial activity after 9 months when stored desiccated in the absence of buffer. An attractive feature with all the biosensors was their ability to effectively screen the endogenous interferents ascorbic acid, uric acid, L-cysteine and acetaminophen. This characteristic, coupled with the high biocompatibility of the polymeric hydrogel composites make these mate rials potential candidates for in-vivo biosensors.