Hydrogels

Hydrogels represent a class of high water content polymers with physical or chemical crosslinks. Their physical properties are similar to soft tissues. Cross linking is a stabilization process in polymer chemistry which leads to multidimensional extension of polymeric chain resulting in network structure. Cross-link is a bond which links one polymer chain to other. It can be ionic or covalent. Cross linking changes a liquid polymer into 'solid' or 'gel' by restricting the ability of movement. When polymer chains are linked together by cross-links, they lose some of their ability to move as individual polymer chains. A liquid polymer (where the chains are freely flowing) can be turned into a 'solid' or 'gel' by cross-linking the chains together. Cross linking increases the molecular mass of a polymer. Cross-linked polymers are important because they are mechanically strong and resistant to heat, wear and attack by solvents. However, the drawback associ...

The development of materials that undergo shape changes occupies a central theme in materials science and has proven important in several applications. Several classes of hydrogels, which are cross-linked water-soluble polymers, can change their properties (such as, volume, cross-link density) in response to temperature, pH value, or ionic strength. These dynamic hydrogels can also be modified with biochemical moieties to give materials that change their properties in response to proteins and ligands. For example, hydrogels that undergo volume changes because of antigen-antibody and lectin-carbohydrate interactions have been used as biosensors. The underlying principle of operation of dynamic hydrogel materials relates to a change in their physical or chemical cross-linking density in response to environmental cues. An unexplored alternative to these approaches relies on the use of a natural protein that undergoes a conformational change as a mechanism to alter the characteristics of a material. The functional importance of protein motions in biological systems, together with the wide range of protein motions that can be harnessed, offers a flexible approach to the preparation of dynamic materials.

In this paper, we present preliminary results showing the response of glucose-sensitive hydrogels, confined in micro-pressure sensors, to the changes in environmental glucose concentration. The glucose concentrations were incrementally varied between 20 and 0mM in 0.15M PBS solution at 7.4 pH and bovine serum at 7.4 pH at room temperature and response of the sensor was recorded. The micro sensors demonstrate a response time of 10 minutes in both PBS and serum. Tissue response after 55 days of subcutaneous implantation of a EtO sterilized sensor in mice is presented. The preliminary analysis of the surrounding tissue shows inflammation which is believed not to interfere with the sensor performance.

3D printing (3DP) technologies have been attracting much recent interest as new methods of fabricating medicines and medical devices. Of the many types of 3DP available, stereolithographic (SLA) printing offers the unique advantage of being able to fabricate objects by cross-linking resins to form networked polymer matrices. Because water can be entrapped in these matrices, it is possible in principle to fabricate pre-wetted, drug-loaded hydrogels and devices. Here, SLA printing was used to prepare ibuprofen-loaded hydrogels of cross-linked polyethylene glycol diacrylate. Hydrogels containing up to 30% w/w water, and 10% w/w ibuprofen, were successfully printed. Dissolution profiles showed that drug release rates were dependent on water content, with higher water content hydrogels releasing drug faster. The conclusion is that SLA 3DP offers a new manufacturing route to pharmaceutical hydrogels.

Extracting high-quality RNA from hydrogels containing polysaccharide components is challenging, as traditional RNA isolation techniques designed for cells and tissues can have limited yields and purity due to physiochemical interactions between the nucleic acids and the biomaterials. In this study, a comparative analysis of several different RNA isolation methods was performed on human adipose-derived stem cells photoencapsulated within methacrylated glycol chitosan hydrogels. The results demonstrated that RNA isolation methods with cetyl trimethylammonium bromide (CTAB) buffer followed by purification with an RNeasy Ò mini kit resulted in low yields of RNA, except when the samples were preminced directly within the buffer. In addition, genomic DNA contamination during reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was observed in the hydrogels processed with the CTAB-based methods. Isolation methods using TRIzol Ò in combination with one of a Qiaex Ò gel extraction kit, an RNeasy Ò mini kit, or an extended solvent purification method extracted RNA suitable for gene amplification, with no evidence of genomic contamination. The latter two methods yielded the best results in terms of yield and amplification efficiency. Predigestion of the scaffolds with lysozyme was investigated as a possible means of enhancing RNA extraction from the polysaccharide gels, with no improvements observed in terms of the purity, yield, or amplification efficiency. Overall, this work highlights the application of a TRIzol Ò + extended solvent purification method for optimizing RNA extraction that can be applied to obtain reliable and accurate gene expression data in studies investigating cells seeded in chitosan-based scaffolds.

The rheological and morphological properties and in vitro theophylline release of tertiary aminebased microgels were evaluated. The testing of such a formulation through in vitro diffusion experiments revealed that the release of theophylline from the microgels was pH-dependent and differs significantly with respect to a nonresponsive gel like scleroglucan (Scl). The microgels were obtained from 2-(diethyl amino) ethylmethacrylate (DEA) in the presence of a bifunctional crosslinker at pH 8-9. As the resulting microgels are pH-responsive and an increase in viscosity from high to low pH range is exhibited, the in vitro release of theophylline as model drug was studied at different pHs of both the matrix and the receptor medium. The release behaviors of PDEA-based microgels were compared to nonresponsive natural gel Scl, studied previously. For microgels, diverse release patterns were found at different acidity conditions. This observation seems to be related to complex diffusion phenomena and the different gel structure obtained for samples prepared at dissimilar pH.

Gellan gum is a hydrogel-forming polysaccharide when combined with monovalent or divalent cations such as sodium, magnesium, potassium or calcium. Commercially, gellan gums are sold with trace amounts of these cations, which have been proven to affect the gelation and mechanical properties of the resultant hydrogels. A new method based on impedance analysis for determining the gel transition temperature of purified and unpurified gellan gum is presented. The sodium salt form of gellan gum is shown to have lower dissolution and gel transition temperatures.

Gum polysaccharides are one of the most abundant bio-based polymers. This study demonstrates the synthesis of locust bean gum-cl-poly (acrylonitrile) based hydrogel were obtained using acrylonitrile monomer, MBA as crosslinker and APS as initiator by involving free radical co-polymerization and crosslinking reaction technique. The factors influencing the adsorption capacities, including the initial concentrations of dye solutions, contact time, initial pH values and dosage of the adsorbent as well as ionic strength of the solution are discussed. The locust bean gum-cl-poly(acrylonitrile) based hydrogel was found to be pH sensitive. The kinetics studies show that the adsorption of the dye fitted a pseudo-second-order equation.

The present work evaluates a newly developed silated hydroxypropylmethylcellulose (Si-HPMC)-based hydrogel as a scaffold for 3D culture of osteogenic cells. The pH variation at room temperature catalyzes the reticulation and self-hardening of the viscous polymer solution into a gelatine state. We designed reticulation time, final consistency and pH in order to obtain an easy handling matrice, suitable for in vitro culture and in vivo injection. Three human osteogenic cell lines and normal human osteogenic (HOST) cells were cultured in 3D inside this Si-HPMC hydrogel. We show here that osteosarcoma cells proliferate as clonogenic spheroids and that HOST colonies survive for at least 3 weeks. Mineralization assay and gene expression analysis of osteoblastic markers and cytokines, indicate that all the cells cultured in 3D into this hydrogel, exhibited a more mature differentiation status than cells cultured in monolayer on plastic. This study demonstrates that this Si-HPMC hydrogel is well suited to support osteoblastic survival, proliferation and differentiation when used as a new scaffold for 3D culture and represents also a potential basis for an innovative bone repair material. r

A new hydrogel that combines poly(ethylene glycol) and β-cyclodextrin has been synthesized. Both components are linked by using a diisocyanate (HDMI), first by end-capping the poly(ethylene glycol) with isocyanate groups an then reacting it with β-cyclodextrin, forming urethane links. Hydrogels of molar compositions (β-cyclodextrin/poly(ethylene glycol)) ranging from 1/4 to 1/14 have been synthesized. These hydrogels swell quickly and their water contents depend upon temperature. The gels are temperature resistant and show an elastomeric behavior. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 1162–1166, 2006

We report the synthesis and characterization as well as cytotoxicity and biocompatibility studies of a poly(magnesium acrylate) hydrogel (PAMgA) developed for drug delivery applications. Two hydrogels with different mesh sizes, large and short, were synthesized (L-C PAMgA and S-C PAMgA). The hydrogels were characterized through swelling, FT-IR and DSC. Cytotoxicity in vitro was evaluated on cell line NIH-3T3 fibroblasts via direct contact and two indirect contact methods (MTT and flow citometry). Both PAMgA hydrogels exhibited low cytotoxicity with survival rates higher than 90%. To select their administration route, biocompatibility was evaluated after intraperitoneal, subcutaneous, and oral administration to mice of both hydrogels at different dose ranges. Swelling percentages obtained were 33.3 ± 4.2% and 166.7 ± 8.3% for L-C PAMgA and S-C PAMgA respectively, showing a great difference in both hydrogels. Among the administration routes assayed, the hydrogels were well tolerated after oral administration of a wide dose range (10-500 mg/kg), thereby indicating that both PAMgA hydrogels are excellent candidates for oral administration due to their in vitro biocompatibility and oral non-toxicity. These results together with the fact that their synthesis is simple and inexpensive make them good candidates for the design of oral drug delivery devices.

Both Laponite and scleroglucan can find several applications in various fields (from industrial to biomedical one) in virtue of their peculiar features and rheological properties displayed in aqueous phases. Structural states of Laponite dispersions strongly depend on concentration and ionic strength. When attractive and repulsive interparticle interactions are so effective that they lead to arrested states (attractive gel or repulsive glass), the rheological behavior of the dispersion undergoes a sharp transition, from quasi-Newtonian to markedly shear thinning and viscoelastic. Conversely, scleroglucan solutions gradually change to weak gels with increasing polymer concentration. The present work is concerned with aqueous Laponite-scleroglucan mixed systems, obtained according to different preparation modes, and is aimed at examining how much the content and proportion of both components affect the viscoelastic and flow properties of the mixed system.

Objective. Comparison of desloughing efficacy after four weeks and healing outcomes after 12 weeks in sloughy venous leg ulcers treated with Manuka honey (Woundcare 18+) vs. standard hydrogel therapy (IntraSite Gel). Background. Expert opinion suggests that Manuka honey is effective as a desloughing agent but clinical evidence in the form of a randomised controlled trial is not available. There is a paucity of research which uses Manuka honey in venous ulcers. Design. Prospective, multicentre, open label randomised controlled trial. Method. Randomisation was via remote telephone. One hundred and eight patients with venous leg ulcers having ‡50% wound area covered in slough, not taking antibiotics or immunosuppressant therapy were recruited from vascular centres, acute and community care hospitals and leg ulcer clinics. The efficacy of WoundCare 18+ to deslough the wounds after four weeks and its impact on healing after 12 weeks when compared with IntraSite Gel control was determined. Treatment was applied weekly for four weeks and follow-up was made at week 12. Results. At week 4, mean % reduction in slough was 67% WoundCare 18+ vs. 52AE9% IntraSite Gel (p = 0AE054). Mean wound area covered in slough reduced to 29% and 43%, respectively (p = 0AE065). Median reduction in wound size was 34% vs. 13% (p = 0AE001). At 12 weeks, 44% vs. 33% healed (p = 0AE037). Wounds having >50% reduction in slough had greater probability of healing at week 12 (95% confidence interval 1AE12, 9AE7; risk ratio 3AE3; p = 0AE029). Infection developed in 6 of the WoundCare 18+ group vs. 12 in the IntraSite Gel group. Conclusion. The WoundCare 18+ group had increased incidence of healing, effective desloughing and a lower incidence of infection than the control. Manuka honey has therapeutic value and further research is required to examine its use in other wound aetiologies. Relevance to clinical practice. This study confirms that Manuka honey may be considered by clinicians for use in sloughy venous ulcers. Additionally, effective desloughing significantly improves healing outcomes.

Gel matrices of scleroglucans from Sclerotium rolfsii ATCC 201126 (EPS I and EPS II, from 48-h and 72-h fermentations, respectively) were evaluated on their release kinetics of theophylline (Th). Equivalent polymer (2%, w/w) and Th (0.2%, w/w) concentrations showed almost coincident drug release patterns, independently of polymer molecular weight or the microstructural properties of gel matrices. Dynamic rheological studies of scleroglucan hydrogel structures (storage, G , and loss, G , moduli) indicated a solid-like behavior. Differences on pore size dimensions (EPS I = 20 m and EPS II = 7 m) were in accordance to the differences in G (EPS I = 113 Pa and EPS II = 161 Pa), a fact likely related to variations in the cross-linking density of polymer networks. Compared to already known biopolymers, EPS I and EPS II at 0.5 g/L showed a good dispersing ability against particulate suspensions of activated charcoal, bentonite, CaCO 3 , celite and quartz powder. Emulsifying ability of both EPSs at 2 g/L was high (E = 56-60%) when tested with kerosene, moderate (∼30%) with hexadecane, and negligible in the presence of olive oil-in-water emulsions. (J.I. Fariña).

An investigation of encapsulated plasmid DNA release from degradable poly(ethylene glycol)-co-poly(gly-colic acid) hydrogels (PEG-co-PGA) is presented. We determined by varying the chemistry of the cross-linker group, significant variations in hydrogel degradation kinetics could be achieved to control the release profiles of plasmid DNA. We prepared three analogues of PEG-co-PGA hydro-gels by a photopolymerization process and measured variation in degradation rates by monitoring mechanical properties and release of plasmid DNA. 1 H 1D DOSY NMR (one-dimensional diffusion ordered nuclear magnetic resonance spectroscopy) was used to measure conversion of vinyl groups after photocross-linking. Nearly full vinyl conversion was reached after 10 min exposure under ultraviolet light. Gel electrophoresis analysis confirmed that plasmid DNA remained structurally intact after photoen-capsulation and release from the gels. This approach provides an additional strategy for controlling the release of biologically active compounds from hydrogels. Ó

Wound healing is a complex process involving an integrated response by many different cell types and growth factors in order to achieve rapid restoration of skin architecture and function. The present study evaluated the applicability of a chitosan hydrogel (CH) as a wound dressing. Scanning electron microscopy analysis was used to characterize CH morphology. Fibroblast cells isolated from rat skin were used to assess the cytotoxicity of the hydrogel. CH was able to promote cell adhesion and proliferation. Cell viability studies showed that the hydrogel and its degradation by-products are noncytotoxic. The evaluation of the applicability of CH in the treatment of dermal burns in Wistar rats was performed by induction of full-thickness transcutaneous dermal wounds. Wound healing was monitored through macroscopic and histological analysis. From macroscopic analysis, the wound beds of the animals treated with CH were considerably smaller than those of the controls. Histological analysis revealed lack of a reactive or a granulomatous inflammatory reaction in skin lesions with CH and the absence of pathological abnormalities in the organs obtained by necropsy, which supported the local and systemic histocompatibility of the biomaterial. The present results suggest that this biomaterial may aid the re-establishment of skin architecture.

A hydrogel was prepared from pullulan and evaluated as a novel biomaterial for vascular engineering. Using a crosslinking process with sodium trimetaphosphate in aqueous solution, homogeneous, transparent, and easyto-handle pullulan gels were obtained with water-content higher than 90%. A circular punch was used to cut 6-mm diameter and 2-mm thickness discs for cell culture. Environmental scanning electron microscopy analysis of hydrated gels revealed a smooth surface, on which rabbit vascular smooth muscle cells were successfully seeded. The absence of cytotoxicity was evidenced by a live/dead assay. Fluorescence-labeled cells were observed adhering and progressively spreading out on the surface of the material. Cellular proliferation was followed for up to 1 week using an MTT assay. In addition, a complete in vitro degradation of the gels was achieved in 3 h upon incubation in a pullulanase solution (44 U/mL). In conclusion, we have shown the feasibility of preparing a biocompatible pullulan-based hydrogel that could support vascular cell culture. Based on these promising results, future studies will focus on the seeding of vascular cells on tubular-shaped hydrogels and the in vivo implantation of these new biomaterials.

This research studied the characteristics of poly(acrylamide) and methylcellulose (PAAm-MC) hydrogels as a novel adsorbent material for removal of pesticide paraquat, from aqueous solution, with potential applications in curbing environmental risk from such herbicides. PAAm-MC hydrogels with different acrylamide (AAm) and MC concentrations were prepared by a free-radical polymerization method. The capability of the hydrogels in removing paraquat dichloride from aqueous solution was determined using UV-Vis analysis. The scanning electron microscopy method was used to study the morphological properties of the hydrogels, and swelling degree (Q) of the hydrogels was also measured. The entrapped MC in PAAm chains provoked significant changes in morphological, hydrophilic, and adsorption properties of the PAAm-MC hydrogels. The adsorption capacity of hydrogels was strongly influenced by AAm, MC, and paraquat concentrations with the highest adsorption capacity (q eq ¼ 14.3 mg g À1) was observed for hydrogels synthesized with 6.0% AAm with 0.75% MC swollen in 45.7 mg L À1 of paraquat solution. Freundlich model performed better than Langmuir model in describing the adsorption isotherm of PAAm-MC/paraquat system, implying a heterogeneous surface. These results suggest that PAAm-MC hydrogels are potentially viable absorbents for removal of paraquat pesticide from aqueous solution and cleaning water contaminated with dyes, heavy metals, and others pesticides. V

This report was prepared as an account of work sponsored by an agency of the United States Government. Neither the United States Government nor any agency thereof, nor any of their employees, makes any warranty, express or implied, or assumes any legal liability or responsi. bility for the accuracy, completeness, or uselulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States Government or any agency thereof. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States Government or any agency thereof.

Carrageenans are highly sulphated galactans, well-known for their thermogelation properties which have been extensively exploited in food and cosmetics industry but poorly explored in the biomedicine field. In this study, we have assessed the in vitro and in vivo biocompatibility of j-carrageenan hydrogels that have been explored for regenerative medicine and tissue engineering applications. The in vitro cytotoxicity of the materials using a L929 mouse fibroblast cell line was evaluated, and the effect of j-carrageenan hydrogels on the activation of human polymorphonuclear neutrophils cells (hPMNs) was also evaluated by the quantification of reactive oxygen species by chemiluminescence.

Glucose-selective holographic sensors were fabricated from unique tetrahedral 2-acrylamidophenylboronic acid (2-APB) incorporated with co-monomers poly(ethylene glycol) acrylate (PEG), (3-acrylamidopropyl)trimethylammonium chloride (ATMA) and [2-(acryloyloxy)ethyl]trimethylammonium chloride (AETA) into thin hydrogel films which were transformed into volume holograms using a diffusion method coupled with holographic recording using a frequency-doubled Nd:YAG laser (532 nm). The results showed that the 2-APB-based holographic sensors contracted upon addition of glucose due to the formation of a 2:1 complex between the tetrahedral 2-APB and glucose. More significantly, the 2-APB-based holographic sensors had greatly reduced lactate dependence and a hugely reduced pH effect over the physiological range of pH. These features are vital for development of contact lens-based glucose sensor, where the pH variability is greater (pH 5.8-7.8) and the lactate concentration is substantially higher than in blood. Furthermore, the 2-APB-based holographic sensors also displayed fast response to glucose. The successful union of holograms and the tetrahedral 2-APB receptor for glucose detection in artificial tear fluid is also demonstrated. This new type of holographic sensors responding to glucose with features of minor pH effect and negligible interference from lactate is applicable to the detection of glucose concentrations in tear fluid for the management of diabetes.

In this work, we investigated the design and fabrication of porous polyacrylamide hydrogels via a thermal reverse-casting technique. The porous hydrogels were prepared by the free-radical crosslinking polymerization of the monomer solution within the space of an agarose gel, which after the setting of the chemical gel, was removed to allow for the formation of an interconnected porosity pathway. Two different agarose/monomer solution ratios were selected to modulate the porosity of the hydrogels, and the as-obtained samples were characterized in terms of their chemical structure, morphology, thermal properties, and swelling behavior in different ionic strength solutions. The results of this study demonstrate that the reverse-casting process enhanced the solventretaining capability of the hydrogels and that their swelling ratio increased with increasing concentration of the agarose solution in the initial formulation. All of these results finally demonstrate that the pore structure features played a key role in defining the swelling behavior of the hydrogels.

Poly(N-vinyl-2-pyrrolidone) (PVP) is widely used in medicine due to its high biocompatibility. In this study, itaconic acid (IA) was co-polymerized with N-vinyl-2-pyrrolidone (NVP) monomer to prepare the pH sensitive hydrogels. These copolymer hydrogels were prepared using ultra-violet (UV) induced methods at ambient temperature. Monomer and cross-linking agent (N,N -methylene-bisacrylamide (MBAAm)) concentration effects on preparation of this copolymer hydrogel were investigated using swelling, FT-IR, and SEM. The prepared copolymer hydrogel is highly pH sensitive. The percentage swell of the copolymer hydrogels was found to increase from 150 to 3011% as the pH value of the swelling solution varied from 4 to 10. These pH sensitive copolymer hydrogels present a promising approach for drug delivery applications.

A novel, regenerative and biodegradable acrylic acid hydrogel having different chitosan composition (w = 0, 0.5, 1.0 and 1.5 %) was constructed using gamma radiation from the Cobalt-60 source. The prepared hydrogel was treated with alkali to enhance its dye adsorption capacity. Uptake capability of the hydrogel at different chitosan percentage, contact time, pH, and methylene blue (MB) concentrations was measured using UV Spectrometer. MB uptake ability obtained was found to escalate proportionately with escalating chitosan percentage and alkali treatment. Kinetics and isotherm of MB adsorption mechanism were analyzed. Pseudosecond- order model and Langmuir isotherm model were followed by the Hydrogel MB uptake capacity. The adsorption efficiency of monolayer saturation of the alkali-treated adsorbent was 322 mg/g as obtained from Langmuir equation. Desorption and reuses of the hydrogel were successfully carried out. The results indicated that acrylic acid-chitosan hydrogel is feasi...

Biomaterials constructed from self-assembling peptides, peptide derivatives, and peptide-polymer conjugates are receiving increasing attention as defined matrices for tissue engineering, controlled therapeutic release, and in vitro cell expansion, but many are constructed from peptide structures not typically found in the human extracellular matrix. Here we report a self-assembling biomaterial constructed from a designed peptide inspired by the coiled coil domain of human fibrin, the major protein constituent of blood clots and the provisional scaffold of wound healing. Targeted substitutions were made in the residues forming the interface between coiled coil strands for a 37amino acid peptide from human fibrinogen to stabilize the coiled coil peptide bundle, while the solvent-exposed residues were left unchanged to provide a surface similar to that of the native protein. This peptide, which self-assembled into coiled coil dimers and tetramers, was then used to produce triblock peptide-PEG-peptide bioconjugates that self-assembled into viscoelastic hydrogel biomaterials.

Alginate has been widely used in a variety of biomedical applications including drug delivery and cell transplantation. However, alginate itself has a very slow degradation rate, and its gels degrade in an uncontrollable manner, releasing high molecular weight strands that may have difficulty being cleared from the body. We hypothesized that the periodate oxidation of alginate, which cleaves the carbon-carbon bond of the cisdiol group in the uronate residue and alters the chain conformation, would result in promoting the hydrolysis of alginate in aqueous solutions. Alginate, oxidized to a low extent (∼5%), degraded with a rate depending on the pH and temperature of the solution. This polymer was still capable of being ionically cross-linked with calcium ions to form gels, which degraded within 9 days in PBS solution. Finally, the use of these degradable alginate-derived hydrogels greatly improved cartilage-like tissue formation in vivo, as compared to alginate hydrogels. *

Cyclosporine A (CyA) is an immunosuppressant drug that is used for treating a variety of ocular diseases and disorders. CyA is commonly delivered via eye drops, which is highly inefficient due to a low bioavailability of less than 5%. The bioavailability of ophthalmic drugs can be substantially improved to about 50% by delivering them via contact lenses. This paper focuses on the development of nanostructured poly (2-hydroxyethyl methacrylate) (p-HEMA) hydrogels containing microemulsions or micelles of Brij 97 (C 18 H 35 (OCH 2 CH 2 ) 10 ) for extended delivery of CyA. Release of CyA from these nanostructured hydrogels was performed in vitro to explore the mechanisms of release and the effects of surfactant concentration, processing conditions and storage on the release kinetics. Results show that the surfactant and microemulsion-laden gels can deliver CyA at therapeutic dosages for a period of about 20 days. Release of the drug is diffusion controlled with effective diffusivities decreasing with increasing surfactant loading. The release kinetics are relatively similar for both surfactant and microemulsion-laden gels with comparable surfactant loading. The results also show that these hydrogels retain their effectiveness even after exposure to all the relevant processing conditions including unreacted monomer extraction, autoclaving and packaging, and so these materials seem to be very promising for ophthalmic delivery of CyA and perhaps other drugs.

This work describes the fabrication, characterization, and biological evaluation of a thin protein-resistant poly(ethylene glycol) (PEG)-based hydrogel coating for antifouling applications. The coating was fabricated by free-radical polymerization on silanized glass and silicon and on polystyrene-covered silicon and gold. The physicochemical properties of the coating were characterized by infrared spectroscopy, ellipsometry, and contact angle measurements. In particular, the chemical stability of the coating in artificial seawater was evaluated over a six-month period. These measurements indicated that the degradation process was slow under the test conditions chosen, with the coating thickness and composition changing only marginally over the period. The settlement behavior of a broad and diverse group of marine and freshwater fouling organisms was evaluated. The tested organisms were barnacle larvae (Balanus amphitrite), algal zoospores (UlVa linza), diatoms (NaVicula perminuta), and three bacteria species (Cobetia marina, Marinobacter hydrocarbonoclasticus, and Pseudomonas fluorescens).

Cyclic acetal hydrogels are a novel group of biomaterials which may facilitate osteogenic differentiation of encapsulated bone marrow stromal cells (BMSCs) because of their neutral degradation products. Here, we have incorporated hydroxyapatite nanoparticles within cyclic acetal hydrogels to create cyclic acetal nanocomposites for craniofacial tissue engineering applications. We hypothesized that inclusion of nanosized hydroxyapatite particles within cyclic acetal hydrogels would upregulate osteogenic signal expression of encapsulated BMSCs, due to enhanced cell adhesion, and therefore promote osteodifferentiation. Experimental nanocomposite groups consisted of lower (5 ng/mL) and higher (50 ng/mL) concentrations of nanoparticles. The nanocomposites were characterized by scanning electron microscopy, transmission electron microscopy, and energy dispersive spectroscopy. Swelling parameters of hydrogels in the presence of nanoparticles was studied. Osteoblastic differentiation was characterized by alkaline phosphatase (ALP) and osteocalcin (OC) expression, whereas endogenous osteogenic sig-nal expression was characterized by morphogenetic protein-2 (BMP-2) expression. Finally, immunohistochemistry was performed to detect the presence of OC at the protein level. Results indicated that hydroxyapatite nanoparticles were uniformly distributed throughout the hydrogels and did not affect material properties of the gels. Viability of cells was not affected by nanoparticle concentration, and BMP-2 and OC mRNA expression was enhanced in the presence of nanoparticles. However, a difference in BMP-2, ALP, and OC mRNA expression was not noted between the lower and higher concentrations of nanoparticles. This work demonstrates that inclusion of hydroxyapatite nanoparticles within a cyclic acetal nanocomposite hydrogel may enhance BMSC differentiation by promoting endogenous osteogenic signal expression.

To determine the impact of incubation solution composition on protein deposition to silicone hydrogel (SH) contact lenses using a simplistic and a complex model of the tear film. Three SH materials--senofilcon A (SA), lotrafilcon B (LB), and balafilcon A (BA)--were incubated in two different solutions; Solution A was a simplistic augmented buffered saline solution containing a single protein, whereas Solution B was a complex artificial tear solution (ATS), containing the augmented buffered saline solution in addition to proteins, lipids, and mucins (pH=7.4). The proteins of interest (lysozyme, lactoferrin, albumin) were radiolabeled with Iodine-125 (2% protein of interest) and the accumulation of the conjugated protein to the lens materials was determined after 1, 7, 14, and 28 days of incubation. Protein deposition was measured using a gamma counter and the raw data were translated into absolute amounts (µg/lens) via extrapolation from standards. After 28 days, lysozyme uptake was ...

Xanthan is a well-known biopolymer. It is an anionic polysaccharide, whose primary structure depends on the bacterial strain and fermentation conditions. Xanthan was extensively studied in combination with galactomannans, and over 90 patents cover the technology of this preparation. Our aim was to investigate the relation between the physical properties of a xanthan matrix in the absence or presence of calcium ions and its influence on the release of pentoxifylline. The release of pentoxifylline from xanthan tablets in purified water was shown to be very slow and governed by the process of polymer relaxation. The presence of calcium ions significantly increased the drug release, changing the release mechanism into a more diffusion controlled one. Xanthan matrices showed substantially faster and more extensive swelling in water than in the presence of Ca 2+ ions. Surprisingly, negative correlation between drug release and degree of swelling was obtained for xanthan: the higher the swelling, the slower the drug release. Higher ionic strength led to lower erosion of xanthan tablets, and the gel layers formed were more rigid and of firmer texture, as shown by rheological experiments and textural profiling. The results indicate that the presence of Ca 2+ ions in the solution or in matrices does not cause crosslinking of xanthan polymers, but causes charge screening of ionized groups on the trisaccharide side chains of xanthan, leading to lower inter-molecular repulsion and changing water arrangement. The understanding of the parameters influencing drug release leads to the conclusion that xanthan is suitable for controlled release formulations, especially with the incorporation of certain small counterions.

The release of locally acting drugs can be targeted using mucoadhesive platform. Natural biodegradable polymers are considered as suitable contenders as mucoadhesive polymers. The aim of current research was to evaluate mucoadhesive role of agarose (AG) by preparing directly compressible tablets. AG was aided by carbopol ® (CP) for simultaneous release of benzocaine (BZN) and tibezonium iodide (TIB) from mucoadhesive tablets. In order to prepare tablets, ingredients were mixed geometrically and compressed using a ZP35 rotary tablet machine. The prepared tablets were characterized for physical, ex vivo mucoadhesive time (ET) and mucoadhesive strength (MS), swellability, erosion and in vitro drugs release. The solid state studies revealed that no unusual peak in the physical mixture of ingredients through FTIR and DSC analysis. Values of weight variation and friability tests of the tablet formulations complied with USP specifications which showed that variation in the polymers did not affect physical parameters of the tablets. The highest ET (24.3 h) and MS (22.6 g) values were associated with formulation T9. Maximum erosion was observed in T1 formulation with lowest concentration of AG (10%) used in the study. Similarly, higher SI was observed with T2 (74.02%) at 6 h. The optimized tablet formulation T2 showed complete drug release after 6 h with better swelling. In addition, when polymers were used alone, AG exhibited poor MS and ET values compared to CP whereas polymers used in combination (AG-CP) exhibited much better properties. Therefore, it was concluded that AG when combined with a mucoadhesive agent like CP have much improved potential to effectively deliver drugs. RESUMEN. RESUMEN. La liberación de fármacos de acción local puede orientarse utilizando una plataforma mucoadhesiva. Los polímeros biodegradables naturales se consideran contendientes adecuados como polímeros mucoadhesivos. El objetivo de la investigación actual fue evaluar el papel mucoadhesivo de la agarosa (AG) mediante la preparación de tabletas comprimibles directamente. AG fue asistido por carbopol® (CP) para la liberación simultánea de benzocaína (BZN) y yoduro de tibezonio (TIB) de tabletas mucoadhesivas. Para preparar las tabletas, los ingredientes se mezclaron geométricamente y se comprimieron utilizando una máquina rotatoria de tabletas ZP35. Los comprimidos preparados se caracterizaron por el tiempo mucoadhesivo (ET) físico y ex vivo y la fuerza mucoadhesiva (MS), capacidad de hinchamiento, erosión y liberación de fármacos in vitro. Los estudios de estado sóli do revelaron que no hubo un pico inusual en la mezcla física de ingredientes a través del análisis FTIR y DSC. Los valores de las pruebas de variación de peso y friabilidad de las formulaciones de las tabletas cumplieron con las especificaciones de la USP que mostraron que la variación en los polímeros no afectó los parámetros físicos de

In the present work, we attempted to design a transdermal system for delivering selegiline using a hydrogel-based drug reservoir and a rate-controlling membrane (Solupor polyethylene membranes). The appearances of these preparations were evaluated by scanning electron microscopy (SEM), and the in vitro skin permeation of selegiline across porcine skin was examined. Both the R- and S-forms of selegiline were examined in this study to elucidate the stereoselectivity of skin to selegiline. Solupor membranes and hydrogels exhibited a cross-linking structure with micropores. R-Selegiline revealed a flux of 1.13 microg/cm(2)/h across porcine skin. Solupor membranes were rate limiting for skin permeation of selegiline. Around a 2-fold reduction in the drug flux was determined after Solupor membrane incorporation. There were no significant differences in drug flux across the four Solupor membranes tested. The flux of R-selegiline from cellulose hydrogels approximated that from the aqueous solution (control). Both the membrane and hydrogel greatly reduced the inter-subject variations in skin permeation. According to the results of skin permeation and the partition coefficient between the skin and water (logP(skin/water)), the S-enantiomer may be preferable for permeation into the skin. However, the R- and S-forms demonstrated equal absorption of the drug fluxed in the presence of the membrane and/or the hydrogel. The results of this study encouraged us to further investigate hydrogel-membrane delivery systems for transdermal selegiline administration.

Ketorolac tromethamine is a non-steroidal anti-inflammatory drug that has two major problems when administered orally; it has
severe gastrointestinal side effects as bleeding, peptic ulcer, perforation. Second, it has short half-life (4hr) so require frequent
administration. The aim of this study was to overcome these two problems through preparation of this drug as topical hydrogel.
Hydroxypropyl, hydroxylpropylmethyl, and sodiumcarboxymethyl were the three cellulosic polymers used as gelling agents, the
influence of type and concentration of them on the release of ketorolac was investigated. Oleic acid, tween 80, carveol, and
isopropyl alcohol were used as penetration enhancers, and effect of these enhancers on diffusion of ketorolac across semipermeable
membrane was tested. The optimized formula was evaluated for its anti- inflammatory action on carragenan induced rat
paw edema model. Results revealed that the hydrogel formulations exhibited high drug release especially at low polymer
concentration and the release was follow diffusion controlled mechanism. All enhancers showed enhancement in ketorolac
penetration specially the optimized formula contain Ketorolac 2%, HPMC 1%, and 0.5% Tween 80, which exhibited improved antiinflammatory
activity. So it can be concluded that topical hydrogel enhanced permeation of ketorolac and given an effective antiinflammatory
activity, with avoidance of GIT adverse effect.

Hyaluronic acid (HA) has been crosslinked in solution with glutaraldehyde (GTA), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), poly(ethylene glycol) diglycidylether (EX 810), and divinyl sulfone (DVS) to form hydrogels. Flory-Rehner calculations were used to determine molecular weight between crosslinks (M c), the crosslink density (V e), and mesh size (e) of crosslinked hydrogels after 24-h swelling in distilled water. Generally, lower molecular weight films gave rise to decreased molecular weights between crosslinks as well as increased effective crosslink densities and decreased mesh size. The effects of pH and salt concentration were evaluated. Use of lower molecular weight HA gave rise to decreased molecular weights between crosslinks as well as increased effective crosslink densities and decreased mesh size. Water diffusion coefficients were measured for DVS and GTA hydrogels and were found to be 1.4 3 10 210 and 1.8 3 10 210 m 2 s 21. Autocrosslinked and HA polyethyleneimine gels were also produced but had very limited stabilities compared with the covalently crosslinked materials.

3D printed biomaterials with spatial and temporal functionality could enable interfacial manipulation of fluid flows and motile cells. However, such dynamic biomaterials are challenging to implement since they must be responsive to multiple, biocompatible stimuli. Here, we show stereolithographic printing of hydrogels using noncovalent (ionic) crosslinking, which enables reversible patterning with controlled degradation. We demonstrate this approach using sodium alginate, photoacid generators and various combinations of divalent cation salts, which can be used to tune the hydrogel degradation kinetics, pattern fidelity, and mechanical properties. This approach is first utilized to template perfusable microfluidic channels within a second encapsulating hydrogel for T-junction and gradient devices. The presence and degradation of printed alginate microstructures were further verified to have minimal toxicity on epithelial cells. Degradable alginate barriers were used to direct collect...

A simple and effective technique of improving delivery of hydrophobic drugs from swellable systems is presented. Conventional methods of drug loading in hydrogel systems are limited by the characteristics of the pharmacological agent. The approach we present uses complexants to modulate drug release. Crosslinked poly(ethylene glycol) (PEG) hydrogels were synthesized, characterized, and used for vascular applications. The release of cyclosporine (CyA) from PEG hydrogels is significantly altered by the sterilization techniques. It was hypothesized that the release of CyA from PEG hydrogels can be modulated by using complexants. A cyclodextrin–CyA complex solution was prepared and used for drug loading. The sterilized PEG hydrogels that were loaded using the cyclodextrin–CyA complex solution had favorable release characteristics compared with the release from PEG hydrogels that were loaded using the conventional technique. Hence, drug release from swellable systems can be tailored by the application of this strategy. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005

Two types of hydrophilic networks with conjugated beta-cyclodextrin (␤-CD) were developed with the aim of engineering useful platforms for the localized release of an antimicrobial 5,6-dimethoxy-1indanone N4-allyl thiosemicarbazone (TSC) in the eye and its potential application in ophthalmic diseases. Poly(2-hydroxyethyl methacrylate) soft contact lenses (SCLs) displaying ␤-CD, namely pHEMA-co-␤-CD, and super-hydrophilic hydrogels (SHHs) of directly cross-linked hydroxypropyl-␤-CD were synthesized and characterized regarding their structure (ATR/FT-IR), drug loading capacity, swelling and in vitro release in artificial lacrimal fluid. Incorporation of TSC to the networks was carried out both during polymerization (DP method) and after synthesis (PP method). The first method led to similar drug loads in all the hydrogels, with minor drug loss during the washing steps to remove unreacted monomers, while the second method evidenced the influence of structural parameters on the loading efficiency (proportion of CD units, mesh size, swelling degree). Both systems provided a controlled TSC release for at least two weeks, TSC concentrations (up to 4000 g/g dry hydrogel) being within an optimal therapeutic window for the antimicrobial ocular treatment. Microbiological tests against P. aeruginosa and S. aureus confirmed the ability of TSC-loaded pHEMA-co-␤-CD network to inhibit bacterial growth.

In order to protect implanted glucose sensors from biofouling, novel hydrogels (146-217% water by mass) were developed based on a copolymer of hydroxyethyl methacrylate (HEMA) and 2,3-dihydroxypropyl methacrylate (DHPMA). The porosity and mechanical properties of the hydrogels were improved using N-vinyl-2-pyrrolidinone (VP) and ethyleneglycol dimethacrylate (EGDMA). The results of SEM and DSC FT-IT analyses showed that the hydrogel (VP30) produced from a monomeric mixture of 34.5% HEMA, 34.5% DHPMA, 30% VP and 1% EDGMA (mol%) had an excellent pore structure, high water content at swelling equilibrium (W eq = 166% by mass) and acceptable mechanical properties. Two kinds of VP30-coated sensors, Pt/GOx/VP30 and Pt/GOx/epoxy-polyurethane (EPU)/VP30 sensors were examined in glucose solutions during a period of 4 weeks. The Pt/GOx/VP30 sensors produced large response currents but the response linearity was poor. Therefore, further studies were focused on the Pt/GOx/EPU/VP30 sensors. With a diffusion-limiting epoxy-polyurethane membrane, the linearity was improved (2-30 mM) and the response time was within 5 min. Eight Pt/GOx/EPU/VP30 sensors were subcutaneously implanted in rats and tested once per week over 4 weeks. All of the implanted sensors kept functioning for at least 21 days and 3 out of 8 sensors still functioned at day 28. Histology revealed that the fibrous capsules surrounding hydrogel-coated sensors were thinner than those surrounding Pt/GOx/EPU sensors after 28 days of implantation.

Poly(vinyl alcohol) cryogels are physically cross-linked hydrogels formed through one or more freezing
and thawing cycles with an aqueous polymer solution. As well as being highly biocompatible, the resulting
gels have attractive characteristics in terms of tissue mimicking mechanical properties. They also possess
the added benefi t that these properties can be fi ne-tuned through material parameters (such as solution
concentration) and processing properties (such as number of freeze–thaw cycles or rate of thawing). There
has been signifi cant effort to take advantage of the inherent potential of these gels for tissue replacement
applications through cryogelation process enhancements, formation of composite gels, and the development
of cell encapsulation protocols. These developments can modify pore architecture and alignment, enhance
cell attachment, and bioactivity or enable the formation of cell laden cryogels as part of the freezing and
thawing process. This entry reviews each of these areas, making particular reference to areas of application
for cardiovascular and orthopedic implant and tissue engineering therapies, and also to diabetes treatment.

Hydrogels are cross-linked polymeric networks, which have the ability to hold water within the spaces available among the polymeric chains. The hydrogels have been used extensively in various biomedical applications, e.g., drug delivery, cell carriers and/or entrapment, wound management and tissue engineering. Though far from extensive, this article has been devoted to study the common methods used for the characterization

Softens® (polymacon) contact lenses of 151
patients randomly selected by three American
practitioners were analyzed by the Bausch &
Lomb Soflens Division for possible changes in
physical and chemical properties resulting
from lens usage which averaged 11.3 months.
No significant changes in lens properties.
including the parameters, were noted. The
incidence of surface changes classified as
deposits. damage, or particles are given.