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Heparan sulfates are complex polysaccharides belonging to the family of glycosaminoglycans that participate to the regulation of cell behavior and tissue homeostasis. The biological activities conferred to heparan sulfates are largely dependent on the content and positioning of the sulfate groups along their saccharidic units. At present, identification of particular sulfation patterns in biologically relevant heparan sulfate sequences remains challenging. Although several approaches for structure analysis exist, the complexity of heparan sulfates makes new and original approaches still required. Here, we used molecular imprinting technologies to prepare a library of polyethylene glycol acrylate functionalized hydrogels with the aim to investigate their applicability as specific recognizing systems for fondaparinux, a synthetic pentasaccharide analog to the antithrombin binding site of heparin. Adequate choice of the hydrogel composition and controlling rebinding conditions were important determinants for improving the sulfated oligosaccharide recognition specificity and selectivity. Our results suggest that molecular imprinting approaches could be a possibility for the specific recognition of biologically active sequences in heparan sulfates., (Copyright © 2016 John Wiley & Sons, Ltd.)

An injectable biodegradable hydrogel was prepared for temperature-responsive pulsatile release of insulin. Triblock copolymer of poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) was prepared by ring opening bulk copolymerization and characterized using FT-IR, (1) HNMR, and gel permeation chromatography. Aqueous solution of PECE formed an injectable hydrogel, which was solution at room temperature and transformed into gel at 37°C. The temperature-responsive sol-gel transition and crystallinity of PECE hydrogel was studied and compared with pluronic, a well-studied nonbiodegradable injectable hydrogel. In vitro release study revealed that insulin release profile of PECE was similar to pluronic, and its viscosity was 1/30(th) of pluronic sol at 10,000 s(-1) shear rate. Release behavior of insulin from PECE hydrogels followed Fickian diffusion of first order. Insulin retained its secondary structure after release as confirmed by circular dichroism spectrum. A threefold increase in Fickian diffusion coefficient was evidenced when temperature was increased from 34 to 40°C because of crystalline melting of PCL part of PECE. Pulsatile release of insulin showed a correlation coefficient of 0.90 with the change of temperature., (Copyright © 2013 Wiley Periodicals, Inc.)

Acid functional hydrogels are a type of materials with many advantages. Over the last years, increasing attention for the synthesis of dendronized polymers has been drawn due to their unique properties of high multivalence in the same surface as compared with conventional polymers. In this study, we report the preparation of novel acid dendronized hydrogels using a dendritic monomer obtained from Behera's amine. The swelling and rheological performance, the non-toxicity over fibroblast cells and the drug encapsulation capacity of the novel hydrogels suggests that the new materials can achieve great potential as carrier for drug delivery and other potential biomedical applications., (Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.)

Temperature-sensitive hydrogels are attractive alternatives to porous cell-seeded scaffolds and is minimally invasive through simple injection and in situ gelling. In this study, we compared the performance of two types of temperature-sensitive hydrogels on chondrocytes encapsulation for the use of tissue engineering of cartilage. The two hydrogels are composed of methoxy poly(ethylene glycol)- poly(lactic-co-valerolactone) (mPEG-PVLA), and methoxy poly(ethylene glycol)-poly(lactic- co-glycolide) (mPEG-PLGA). Osmolarity and pH were optimized through the manipulation of polymer concentration and dispersion medium. Chondrocytes proliferation in mPEG-PVLA hydrogels was observed as well as accumulation of GAGs and collagen. On the other hand, chondrocytes encapsulated in mPEG-PLGA hydrogels showed low viability and chondrogenesis. Also, mPEG-PVLA hydrogel, which is more hydrophobic, retained physical integrity after 14 days while mPEG-PLGA hydrogel underwent full degradation due to faster hydrolysis rate and more pronounced acidic self-catalyzed degradation. The mPEG-PVLA hydrogel can be furthered tuned by manipulation of molecular weights to obtain hydrogels with different swelling and degradation characteristics, which may be useful as producing a selection of hydrogels compatible with different cell types. Taken together, these results demonstrate that mPEG-PVLA hydrogels are promising to serve as three-dimensional cell carriers for chondrocytes and potentially applicable in cartilage tissue engineering., (Copyright © 2013 Wiley Periodicals, Inc.)

Collagen hydrogels were prepared via radiation crosslinking. The simulated physiological environmental effects related to their biomedical applications on the volume phase transition of collagen hydrogel were studied, that is stimuli response to ions, temperature, and pH. The deswelling behavior of collagen hydrogel depends on the salt concentration, temperature, pH, and the hydrogel preparation procedure. Meanwhile, hydrogel structure related to the volume phase transition was investigated by FTIR, fluorescence spectrum, and HR-MAS NMR. Deswelling in salt solution caused little change on collagen conformation, and a denser network led to more significant tyrosine-derived fluorescence quenching. Hydrogen bonding between hydrated water and collagen polypeptide chain was dissociated and the activity of hydrophobic side chain increased, inducing a higher extent of contraction with the increasing of salt concentration. Moreover, salt solution treatments weakened the electrostatic interactions, side chains interactions, and hydrogen bonding of collagen hydrogel, which reduced the thermal stability of collagen hydrogel. Comparing with cell-free collagen hydrogel contraction, fibroblasts did not aggravate contraction of collagen hydrogel significantly. This study elucidated the deswelling mechanism of radiation crosslinked collagen hydrogel in simulated physiological environment and provides strategies for controlling the stimuli response of collagen hydrogel in biomedical application., (Copyright © 2012 Wiley Periodicals, Inc.)

Three-dimensional (3D) fibrous hydrogels were fabricated by blending two photoactive polymers, poly(ethylene glycol) diacrylate (PEGDA) and poly(vinyl alcohol) (PVA), and the resulting solution was electrospun. PEGDA is a commonly used hydrogel material for tissue engineering applications since its interaction with cells can be tuned by crosslinking in a variety of bioactive molecules including peptides and proteins. The PVA in these materials aids in fiber formation and stabilizes the fibrous network when hydrated. The average dry fiber diameter in the hydrogels was 1.02 μm and upon swelling, the fiber diameter increased approximately six-fold. Fibers were stable under cell culture conditions for up to 5 days. The adhesive ligand, RGDS, was readily incorporated into the fibrous network via the conjugation of RGDS to PEG-monoacrylate which was then crosslinked with the fibers. The bioactivity of the fibrous hydrogels was compared with peptide-modified PEGDA-based hydrogels. The two hydrogel materials had similar cell adhesion and viability. Cell morphology on the fibrous hydrogels was dendritic showing a more in vivo like representation, as compared to spread cell morphology on the PEGDA gels. The ability to generate 3D fibrous architectures in hydrogel systems opens up new areas of investigation in cell-material interactions and tissue formation., (Copyright © 2011 Wiley Periodicals, Inc.)

This manuscript describes the development of a new porous, flexible bilaminated film for buccal protein administration by a simple and mild casting procedure. It consists of a mucoadhesive layer (chitosan-ethylenediaminetetraacetic acid hydrogel film) containing protein drugs and an impermeable protective layer made of ethylcellose. The obtained mucoadhesive layer was characterized in terms of Fourier transform infrared spectroscopy, rheology, swelling, and mucoadhesion. Rheology results showed that chitosan-ethylenediaminetetraacetic acid hydrogel (10:2) possessed the greatest degree of viscoelasticity and was well-structured compared with other hydrogels. The in vitro mucoadhesion studies also showed that the mucoadhesive force of the hydrogel remained over 17,000 N/m2 during 4 h in the simulated oral cavity. The insulin loaded bilaminated film showed a pronounced hypoglycemic effect following buccal administration to healthy rats, achieving a 17% pharmacological availability compared with subcutaneous insulin injection. According to these results, the bilaminated film would be a promising delivery carrier for protein drugs via the buccal route., (Copyright 2008 Wiley Periodicals, Inc.)

Water-soluble chitosan having double bonds (CS-MA-LA) was synthesized by sequential grafting of methacrylic acid (MA) and lactic acid (LA) via the reaction between amino groups and carboxyl groups under the catalysis of carbodiimide. Its molecular structure was verified by FTIR and (1)H NMR characterizations. Elemental analysis measured grafting ratios of 19% and 10.33% for MA and LA, respectively. CS-MA-LA was readily soluble in pure water and did not precipitate till pH 9. Gelation of the CS-MA-LA was realized by thermal treatment at body temperature under the initiation of a redox system, ammonium persulfate (APS)/N, N,N',N'-tetramethylethylenediamine (TEMED). The gelation time could be mediated in a wide range, e.g. from 6 to 20 min, by reaction temperature and/or initiator's concentration. 3T3 fibroblast culture showed that the cytotoxicity of the hydrogel extractant was dependent on the cell seeding number and the initiator's concentration. With enough number of cells (>2.5 x 10(4)) and low initiator's concentration (5 mM), the cytotoxicity introduced by the initiator is very minimal and negligible. Although the hydrogel could cause acute inflammation and foreign body reaction, no tissue necrosis and malignant infection were evidenced in vivo, demonstrating that the material has better histocompatibility. These features have endowed the chitosan with great opportunity as injectable biomaterials, which may find wide applications in the rapidly developed fields such as tissue engineering and orthopedics.