C. García-Astrain

Biocompatible hydrogel nanocomposite with covalently embedded silver nanoparticles.

Bionanocomposite materials, combining the properties of biopolymers and nanostructured materials, are attracting interest of the wider scientific community due to their potential application in design of implants, drug delivery systems, and tissue design platforms. Herein, we report on the use of maleimide-coated silver nanoparticles (Ag NPs) as cocross-linkers for the preparation of a bionanocomposite gelatin based hydrogel. Diels-Alder cycloaddition of benzotriazole maleimide (BTM) functionalized Ag NPs and furan containing gelatin in combination with additional amide coupling resulted in stable and biocompatible hybrid nanocomposite. The storage moduli values for the hydrogel are nearly three times higher than that of control hydrogel without NPs indicating a stabilizing role of the covalently bound NPs. Finally, the swelling and drug release properties of the materials as well as the biocompatibility and toxicity tests indicate the biomedical potential of this type of material.

Cellulose nanocrystals reinforced environmentally-friendly waterborne polyurethane nanocomposites

Focusing on eco-friendly materials, cellulose nanocrystals (CNC) have gained attention as nanoreinforcement due to their exceptional properties conferred by the elevated length/diameter aspect ratio and high specific mechanical properties. Furthermore, their water dispersibility makes them suitable nanoreinforcements for their incorporation in waterborne polyurethanes (WBPU). The possibility of tailoring the properties by varying the composition and nature of the reagents, opens the opportunity for a wide range of applications. Therefore, in this work a WBPU was synthesized for the preparation of nanocomposite films with different CNC content and the properties of the films were analyzed. The effective incorporation of CNC resulted in an increase in moduli and stress at yield besides in an increased thermomechanical stability, reaching the percolation threshold at a 3wt% CNC as determined theoretically. Nevertheless, above the percolation threshold, the presence of agglomerates reduced slightly these values. The prepared nanocomposites showed increased hydrophilicity after CNC addition.

Diels-Alder "click" chemistry for the cross-linking of furfuryl-gelatin-polyetheramine hydrogels†

This paper deals with the design of biopolymeric hydrogels after the chemical cross-linking of gelatin through the Diels–Alder (DA) reaction. Furan modified gelatin (Gel-FGE) was prepared by the reaction of furfuryl glycidyl ether with the free amino groups present in the gelatin. A Jeffamine®-based bismaleimide was employed as a cross-linking agent and the influence of the amount of cross-linker used on the final hydrogel properties was studied. The DA and retro-DA reactions were followed by ultraviolet spectroscopy and the final properties of the hydrogel assessed. Scanning Electron Microscopy was used to analyze the structure of the final material and rheology studies confirmed the formation of a chemically cross-linked network. The swelling behavior in response to external stimuli such as pH and salt concentration was also studied. By virtue of the DA “click” reaction, biopolymer-based cross-linked hydrogels, with promising properties for biomedical applications, were obtained in a simple one step procedure free of catalysts, additives or coupling agents.

Effect of maleimide-functionalized gold nanoparticles on hybrid biohydrogels properties

The role of well-dispersed gold nanoparticles as cross-linking agents in nanocomposite hydrogel formation was studied. Maleimide-coated gold nanoparticles were synthesized and used for Diels–Alder cycloaddition with furan modified gelatin. Hydrogel formation was aided by additional amide coupling of the modified gelatin with chondroitin sulfate. The cross-linking ability of the functionalized nanoparticles was evaluated and the final hydrogel properties were compared to those of a hybrid hydrogel containing inert-linker coated gold nanoparticles. The storage modulus of the nanoparticle cross-linked nanocomposites was 2.5–3 times compared to the controls. The presence of nanoparticles also affected the swelling properties, resulting in lower swelling ratios due to the formation of the more cross-linked structures. Conducted drug delivery experiments and the study of the light irradiation on the drug release behavior revealed promising features for the applications of nanocomposite polymer for drug delivery.

Designing hydrogel nanocomposites using TiO2 as clickable cross-linkers

Titanium dioxide (TiO2) nanoparticles with clickable functional groups were prepared to allow for the Diels–Alder “click” reaction with a furan-modified pigskin gelatin. Bifunctional dopamine-maleimide linker was employed for TiO2 functionalization with maleimide group. The obtained nanoparticles were characterized using TEM, Zeta potential and FTIR spectroscopy. Functional nanoparticles were subsequently used, together with chondroitin sulphate, as cross-linkers for gelatin hydrogels. Hydrogel controls with bare TiO2 and without nanoparticles were prepared for comparison. The swelling and rheological properties of the nanocomposite hydrogels confirmed the formation of the covalently linked heterogeneous networks. An increase in the storage moduli values was recorded when using maleimide-coated nanoparticles. At the same time, the swelling of the network was significantly reduced indicating the formation of more cross-linked networks. The participation of the surface attached maleimide functional groups through the Diels–Alder cycloaddition was thus confirmed. In addition, hydrogels responded to electrostatic forces as observed by electrostatic force microscopy.

Synthesis and evaluation of functional alginate hydrogels based on click chemistry for drug delivery applications

Environment-sensitive alginate-based hydrogels for drug delivery applications are receiving increasing attention. However, most work in this field involves traditional cross-linking strategies which led to hydrogels with poor long-term stability. Herein, a series of chemically cross-linked alginate hydrogels was synthesized via click chemistry using Diels-Alder reaction by reacting furan-modified alginate and bifunctional cross-linkers. Alginate was successfully functionalized with furfurylamine. Then, 3D architectures were synthesized with water-soluble bismaleimides. Different substitution degrees were achieved in order to study the effect of alginate modification and the cross-linking extent over the behaviour of the hydrogels. The ensuing hydrogels were analysed in terms of microstructure, swelling, structure modification and rheological behaviour. The materials response to external stimuli such as pH was also investigated, revealing a pulsatile behaviour in a large pH range (1-13) and a clear pH-dependent swelling. Finally, vanillin release studies were conducted to demonstrate the potential of these biobased materials for drug delivery applications.

Starch/graphene hydrogels via click chemistry with relevant electrical and antibacterial properties

Starch-based hydrogels were performed by Diels-Alder cross-linking reactions between furan-modified starch and a water soluble bismaleimide, with improving conducting properties by using graphene layers as active nanofillers. The characterization results demonstrated that the Diels-Alder reaction and the corresponding conditions for the hydrogel formation were appropriate. The effect of increasing the furan/maleimide ratio on the architecture of the hydrogels and on the morphological, rheological and swelling properties were thoroughly evaluated. Effective network structure was obtained by increasing the cross-linker content leading to decreasing pore size and increasing storage modulus value of the final material. It was shown that the swelling behavior of hydrogels was mainly governed by the hydrophilic character of bismaleimide. Graphene nanosheets were added for the synthesis of nanocomposite hydrogel and it was characterized in terms of rheological properties, electrical conductivity and antimicrobial activity. The nanocomposite hydrogel presented enhanced mechanical performance, antimicrobial activity and increased conductivity values, up to a decade, indicating that conductive and active hydrogels could be satisfactory obtained, for a large range of potential applications such as biomed.

Innovative Systems from Clickable Biopolymer-Based Hydrogels for Drug Delivery

Biopolymer-based hydrogels have emerged as suitable systems for sustained and targeted drug delivery due to their excellent biocompatibility, biodegradability, hydrophilicity, and tunable microstructure. Even if the use of natural polymers as materials is not new, their use in hydrogel formulations has dramatically grown over the last 10 years. Owing to their chemical versatility, several synthetic approaches can be followed for the design of advanced functionalized materials. The high reactivity, orthogonality, regioselectivity, and mild reaction conditions of “click” reactions render them especially suitable for hydrogel cross-linking. These features are particularly advantageous for the design of drug delivery systems as they prevent interferences with encapsulated drugs or biomolecules while respecting the biocompatibility of the material. The use of click chemistry for the design of biopolymer-based drug delivery systems opens new avenues for the substitution of petroleum-derived polymers and the use of more environmentally friendly chemistries in the pharmaceutical industry.