A Degradable-Renewable Ionic Skin Based on Edible Glutinous Rice Gel.

Traditional wearable devices are commonly nonrecyclable and nondegradable, resulting in energy waste and environmental pollution. Here, a household degradable and renewable ionic skin based on edible glutinous rice gel is developed for a strain, temperature and salivary enzyme activity sensor. This gel depends on intermolecular and intramolecular H-bonds among amylopectin and amylose, and this presents excellent skin-like properties, including stretchability, self-healing property, and adhesion to various substrates. The glutinous rice gel-based skin sensor can be used to monitor vital signs and physiological parameters such as body temperature and heart rate. The sensor also achieves specific speech recognition and detects temperature and body micromovements, which provides the potential to reconstruct language or sensory/motor functions. More importantly, because of the excellent biocompatibility and degradability, the sensor can directly detect the activity of human salivary amylase, which is useful for diagnosing pancreas-, kidney-, and spleen-related diseases in the elderly. Finally, the raw material of ionic skin that originates from traditional grains is degradable and renewable as well as it can be used to prepare household wearable devices. Hence, this work not only extends the application of wearable electronics in daily life but also facilitates health monitoring in the elderly and improves their quality of life.

Long-term antibacterial composite via alginate aerogel sustained release of antibiotics and Cu used for bone tissue bacteria infection.

Bone related-bacterial diseases including wound infections and osteomyelitis (OM) remain a serious problem accompanied with amputation in most severe cases. In this work, we report an exceptional effective antibacterial alginate aerogel, which consists of tigecycline (TGC) and octahedral Cu crystal as an organo-inorganic synergy platform for antibacterial and local infection therapy applications. The alginate aerogel could greatly prolong the release of copper ions and maintain effective antibacterial concentration over 18 days. The result of in-vitro experiments demonstrated that the alginate aerogel has an exceptional effective function on antibacterial activity. Cytotoxicity tests indicated that the alginate aerogel has low biological toxicity (average cell viability >75%). These remarkable results suggested that the alginate aerogel exhibits great potential for the treatment of OM, and has a prosperous future of application in bone tissue engineering.

The effect of dental gel formulation on human primary fibroblasts - an in vitro study.

INTRODUCTION: In ordinary dental practice, the dentist often meets with patients suffering from ulcers, aphtha with edema, bleeding gums, bothersome burning, and dry mouth. These are prosthetic, orthodontic patients, after surgery, in various age ranges. Protefix® gel is a soothing and regenerating preparation aimed at patients with mucosal problems. The aim of our study was to evaluate the protective properties and the safety of Protefix® gel application after dental procedures in vitro. MATERIAL AND METHODS: Human gingival fibroblasts (HGFs) were isolated from normal gingival tissues, cultured to full monolayer and exposed to Protefix® gel in the concentration from 1 to 100%. The viability of cells was examined by MTT assays. Cell migration as a response of treated cells was assessed. The expression of collagen III was estimated by immunocytochemistry after 20 minutes or 24 hours incubation with Protefix® gel. RESULTS: The obtained results indicated that the verified gel significantly stimulated fibroblasts' proliferation, and mitochondrial activity determined by MTT assay increased almost two-fold for lower gel concentrations. The immunohistochemical detection of collagen III revealed an increased expression after incubation with 5% gel. CONCLUSIONS: The results proved that the gel is safe for cells derived from human gingiva and moreover has regenerative properties, which can be of great importance in the treatment of gingivitis after retraction and surgical procedures, or even ordinary daily injuries of oral cavity.

Prosopis juliflora as a new cosmetic ingredient: Development and clinical evaluation of a bioactive moisturizing and anti-aging innovative solid core.

Prosopis juliflora is an invasive plant distributed throughout the world and presents metabolites of interest for cosmetology. The aim of this work was to develop a new polysaccharide-based ingredient from P. juliflora and analyze its application in a solid core formulation that upon contact with water instantly forms a gel to improve moisturizing and anti-aging skin properties. Purified extracts by gel chromatography were characterized by NMR and LC-DAD-MS-MS. The in vitro and in vivo safety, antioxidant activity, formulation development and clinical evaluation were performed. The extract was characterized as containing an α-glucan and phenolics. It was non-cytotoxic, non-phototoxic and no skin reactions were observed in vivo. Antioxidant activity were present through different mechanisms. Clinical evaluation reinforced the potential of P. juliflora in skin hydration and microrelief improvement. This innovative form proved to be a prototype of a new product and the first study of an α-glucan as a cosmetic ingredient.

Soy protein hydrolysate grafted cellulose nanofibrils with bioactive signals for bone repair and regeneration.

TEMPO oxidized cellulose nanofibers (T-CNF) were prepared from cellulose pulp which is extracted from bagasse. Soy protein hydrolysate (SPH) was grafted on T-CNF via amidation of carboxylic groups. Biomineralization was, then, assessed via calcium phosphates (CaP) precipitation in twice-simulated body fluid until formation of a new bioactive material. Protein was efficiently grafted without alteration of morphology and nanofibrils packing as reported by Fourier Transform infrared analysis /X Ray Diffraction /Scanning and Transmission Electron Microscopy / Atomic Force Microscopy. Highly crystalline calcium phosphate deposits - ca. 22.1% - were detected, with a Ca/P ratio equal to 1.63, in agreement with native bone apatite composition. In vitro response of human Mesenchymal Stem Cells confirmed the biocompatibility. No significant differences in terms of cell adhesion were recognized while a significant increase in cell proliferation was detected until 7 days. The presence of calcium phosphates tends to cover the nanofibrillar pattern, inducing the inhibition of cell proliferation and promoting the ex-novo precipitation of mineral phases. All the results suggest a promising use of these biomaterials in the repair and/or the regeneration of hard tissues such as bone.

Polygemcitabine nanogels with accelerated drug activation for cancer therapy.

To overcome the slow activation of gemcitabine, we synthesized a DNA-like polygemcitabine (Ge10) strand through solid-phase synthesis, which not only undergoes rapid intracellular degradation to generate active gemcitabine derivatives, but can also self-assemble into nanogels through molecular recognition, rendering them as promising self-delivered nanodrugs for cancer therapy.

Metal-Organic Framework-Templated Biomaterials: Recent Progress in Synthesis, Functionalization, and Applications.

The integration of a porous crystalline framework with soft polymers to create novel biomaterials has tremendous potential yet remains very challenging to date. Metal-organic framework (MOF)-templated polymers (MTPs) have emerged as persistent modular materials that can be tailored for desired biofunctions. These represent a novel class of hierarchically structured assemblies that combine the advantages of MOFs (precisely controlled structure, enormous diversity in framework topology, and high porosity) with the intrinsic behaviors of polymers (soft texture, flexibility, biocompatibility, and improved stability under physiological conditions). Transformation of surface-anchored MOFs (SURMOFs) via orthogonal covalent cross-linking yields surface-anchored polymeric gels (SURGELs) that open up exciting new opportunities to create soft nanoporous materials. SURGELs overcome the main drawbacks of SURMOFs, such as their limited stability under physiological conditions and their potential to release toxic metal ions, a substantial problem for applications in life sciences. MOF (SURMOF)-templated polymerization processes control the synthesis on a molecular level. Additionally, the morphology of the original MOF crystal template is replicated in the final network polymers. The MOF-templated polymerization can be induced by light, a catalyst, or temperature using several types of reactions, including thiol-ene, metal-free alkyne-azide click reactions, and Glaser-Hay coupling. In the case of photoinduced reactions, the cross-linking process can be locally confined, allowing control of the macroscopic patterning of the resulting network polymer. The use of layer-by-layer (lbl) techniques in the SURMOF synthesis serves the purpose of precise, layer-selective incorporation of functionalities via the combination of the postsynthetic modification and heteroepitaxy strategies. Transforming the functionalized SURMOF into a SURGEL allows the fabrication of polymers with desired bioactive functions at the internal or external surfaces. This Account highlights our ongoing research and inspiring progress in transforming SURMOFs into persistent, modular nanoporous materials tailored with biofunctions. Using cell culture studies, we present various aspects of SURGEL materials, such as the ability to deliver bioactive molecules to adhering cells on SURGEL surfaces, applications to advanced drug delivery systems, the ability to tune cell adhesion via surface modification, and the development of porphyrin-based SURGEL thin films with antimicrobial properties. Then we critically examine the challenges and limitations of current systems and discuss future research directions and new approaches for advancing MOF-templated biocompatible materials, emphasizing the need to include responsive and adaptive functionalities into the system. We emphasize that the hierarchical structure, ranging from the molecular to the macroscopic scale, allows for optimization of the material properties across all length scales relevant for cell-material interactions.

A novel injectable in situ forming gel based on carboxymethyl hexanoyl chitosan/hyaluronic acid polymer blending for sustained release of berberine.

An in situ forming gel based on simply blending carboxymethyl hexanoyl chitosan (CHC) with low molecular weight hyaluronic acid (LMW HA) was developed, without needing cross-linking, photopolymerization or thermal treatments. The CHC/LMW HA blends formed nanoparticles and then rapidly transformed into supermolecular hydrogels under stirring. The gel formation mechanism was examined by Förster resonance energy transfer (FRET). The gels were injectable, cytocompatible and biodegradable, and showed shape-persistent behavior and adhesive property. Berberine, an anti-apoptotic and anti-arthritis naturally occurring compound, was encapsulated within the CHC/LMW HA gels. The gels demonstrated a pH-responsive characteristic which were able to release berberine in a sustained manner at pH 6.0 (simulating inflamed arthritic articular cartilage) and the degradation rates were accelerated at pH 7.4 (simulating healed normal tissue). The berberine-loaded gels effectively protected chondrocytes against sodium nitroprusside-induced apoptosis. The gels may be potentially useful as an injectable system for intra-articular drug delivery and cartilage tissue engineering.

Cell-Membrane-Inspired Silicone Interfaces that Mitigate Proinflammatory Macrophage Activation and Bacterial Adhesion.

Biofouling on silicone implants causes serious complications such as fibrotic encapsulation, bacterial infection, and implant failure. Here we report the development of antifouling, antibacterial silicones through covalent grafting with a cell-membrane-inspired zwitterionic gel layer composed of 2-methacryolyl phosphorylcholine (MPC). To investigate how substrate properties influence cell adhesion, we cultured human-blood-derived macrophages and Escherichia coli on poly(dimethylsiloxane) (PDMS) and MPC gel surfaces with a range of 0.5-50 kPa in stiffness. Cells attach to glass, tissue culture polystyrene, and PDMS surfaces, but they fail to form stable adhesions on MPC gel surfaces due to their superhydrophilicity and resistance to biofouling. Cytokine secretion assays confirm that MPC gels have a much lower potential to trigger proinflammatory macrophage activation than PDMS. Finally, modification of the PDMS surface with a long-term stable hydrogel layer was achieved by the surface-initiated atom-transfer radical polymerization (SI-ATRP) of MPC and confirmed by the decrease in contact angle from 110 to 20° and the >70% decrease in the attachment of macrophages and bacteria. This study provides new insights into the design of antifouling and antibacterial interfaces to improve the long-term biocompatibility of medical implants.

Proteomic analysis of silica hybrid sol-gel coatings: a potential tool for predicting the biocompatibility of implants in vivo.

The interactions of implanted biomaterials with the host organism determine the success or failure of an implantation. Normally, their biocompatibility is assessed using in vitro tests. Unfortunately, in vitro and in vivo results are not always concordant; new, effective methods of biomaterial characterisation are urgently needed to predict the in vivo outcome. As the first layer of proteins adsorbed onto the biomaterial surfaces might condition the host response, mass spectrometry analysis was performed to characterise these proteins. Four distinct hybrid sol-gel biomaterials were tested. The in vitro results were similar for all the materials examined here. However, in vivo, the materials behaved differently. Six of the 171 adsorbed proteins were significantly more abundant on the materials with weak biocompatibility; these proteins are associated with the complement pathway. Thus, protein analysis might be a suitable tool to predict the in vivo outcomes of implantations using newly formulated biomaterials.

Manganese-Based Nanogels as pH Switches for Magnetic Resonance Imaging.

pH-responsive nanogels (NGs) were used to prepare high-efficiency magnetic resonance imaging dual T1/T2 contrast agents for pH imaging. The polymeric NG matrix acts as a strong polydentate ligand that chelates the Mn cations in its inner cavity generating a hybrid NG structure. The Mn chelate NG is sensitive to pH changes, such that protonation induces a change of the polymer hydration state and consequent swelling. The swollen nanogel allows water molecules to enter and interact with the Mn chelate, shortening the relaxation time (switch ON) and giving rise to positive or negative contrast on T1- or T2-weighted magnetic resonance images.

General Toxicity and Antifungal Activity of a New Dental Gel with Essential Oil from Abies Sibirica L.

BACKGROUND The aim of this study was to analyze the antifungal activity and the general toxicity of a new dental gel containing essential oil from the tree Abies sibirica L., which grows in the Republic of Kazakhstan. MATERIAL AND METHODS The essential oil from Abies sibirica L. was obtained by microwave heating method using the STARTE Microwave Extraction System. Adjutants used to prepare the oil were carbomer 974P, glycerin, polysorbate 80, xylitol, triethanolamine, and purified water, all allowed for medical usage. The antifungal activity of the essential oil was assessed by monitoring the optical density of Candida albicans in a microplate reader. The safety was determined by analyzing the acute and subacute toxicity. RESULTS The essential oil obtained by the microwave heating method revealed a higher antifungal activity in comparison with the essential oil obtained by the steam distillation method. No obvious changes were detected in guinea pigs following cutaneous application of the gel. Enteral administration of the essential oil caused minimal functional and histological changes in mice after 4 weeks. The new harmless dental gel containing pine oil from Abies sibirica L. was provided for the purposes of this particular clinical research. CONCLUSIONS The high antifungal activity of the gel is the basis for more in-depth studies on its safety and pharmacological activity.

Liposomal butamben gel formulations: toxicity assays and topical anesthesia in an animal model.

The aim of this study was to evaluate the in vitro cytotoxicity and the in vivo analgesic effect and local toxicity of the local anesthetic butamben (BTB) encapsulated in conventional or elastic liposomes incorporated in gel formulations. The results showed that both gel formulations of liposomal BTB reduced the cytotoxicity (p < 0.001; one-way ANOVA/Tukey's test) and increased the topical analgesic effect (p < 0.05; one-way ANOVA/Tukey's test) of butamben, compared to plain BTB gel. The gel formulations presented good rheological properties, and stability assays detected no differences in physicochemical stability up to 30 d after preparation. Moreover, histological assessment revealed no morphological changes in rat skin after application of any of the gel formulations tested.

Supramolecular Gels by Design: Towards the Development of Topical Gels for Self-Delivery Application.

Following a supramolecular synthon approach, simple salt formation has been employed to gain access to a series of supramolecular gelators derived from the well-known non-steroidal anti-inflammatory drug (NSAID) ibuprofen. A well-studied gel-inducing supramolecular synthon, namely primary ammonium monocarboxylate (PAM), has been exploited to generate a series of PAM salts by reacting ibuprofen with various primary amines. Remarkably, all of the salts (S1-S7) thus synthesized proved to be good to moderate gelators of various polar and nonpolar solvents. Single-crystal and powder X-ray diffraction studies established the existence of the PAM synthons in the gel network, confirming the efficacy of the supramolecular synthon approach employed. Most importantly, the majority of the salts (S2, S3, S6, and S7) were capable of gelling methyl salicylate (MS), an important ingredient found in many commercial topical gels. In vitro experiments (MTT and PGE2 assays) revealed that all of the salts (except S3 and S7) were biocompatible (up to 0.5 mm concentration), and the most suited one, S6, displayed anti-inflammatory ability as good as that of the parent drug ibuprofen. A topical gel of S6 with methyl salicylate and menthol was found to be suitable for delivering the gelator drug in a self-delivery fashion in treating skin inflammation in mice. Histological studies, including immunohistology, were performed to further probe the role of the gelator drug S6 in treating inflammation. Cell imaging studies supported cellular uptake of the gelator drug in such biomedical application.

Ocular biocompatibility of polyquaternium 10 gel: functional and morphological results.

This paper deals with the characterization study of topical and intraocular biocompatibility and toxicity of cationic hydroxyethylcellulose Polyquaternium 10 (PQ10). It also evaluates the rheological properties of gels. The cytotoxicity assays were done in two cell lines: HEp-2 and VERO (human larynx epidermoid carcinoma cell and African green monkey kidney cells respectively). For the in vivo study, New Zealand albino rabbits were used. The in vitro cytotoxic activity of PQ10 shows no statistically significant differences in relation to the control of hydroxypropylmethylcellulose (HPMC) in any of the cell lines used in this study. Similarly, the signs of inflammation observed after treatment showed no significant difference between the groups of animals treated with the polymer compared to the control group. Normal histological characteristics were seen in both groups with no histological inflammatory reaction. After 1 month of the intracameral application of 2% PQ10 (treatment group) or 0.3% HPMC (control group), electroretinograms showed similar levels of a- and b-waves latencies and amplitude. In summary, PQ10 gel was well tolerated in these experiments, with proper monitoring, it could stand as a new alternative in the development of ophthalmic viscosurgical devices.

Dual action antimicrobial surfaces via combined nitric oxide and silver release.

Recent research has demonstrated that silver sulfadiazine and small molecule nitric oxide (NO) donors kill a number of bacterial species synergistically in solution-based assays. Herein, we report on multilayered silica-based xerogels that release both NO and silver. Release of each agent was achieved by exposing amine-modified xerogels to high pressures of NO, and doping silver nitrate (AgNO3) into an alkyl-silane xerogel. Total achievable releases were 3.5 µmol cm(-2) and 1.7 ppm for NO and Ag+, respectively, with release of each agent controlled independent of the other. The NO/Ag+-releasing coating reduced bacterial adhesion and exhibited greater-than-additive killing against both Pseudomonas aeruginosa and Staphylococcus aureus. In contrast, cytotoxicity assays against L929 fibroblasts suggest that the combination does not cause greater-than-additive killing to mammalian cells. Such materials may prove useful in the design of biomedical devices prone to infection such as bone and surgical screws.

Injectable and photocross-linkable gels based on gellan gum methacrylate: a new tool for biomedical application.

In this work, a natural polysaccharide gellan gum (GG) has been modified with methacrylic groups (GG-MA) and combined with polyethylene glycol dimethacrylate (PEG-DMA) in order to create novel injectable hydrogels that can be easily delivered through a needle and photocross-linked in the injection site. A novel synthetic procedure for methacrylation of GG has been proposed to better control its derivatization. Different degrees of functionalization have been achieved and their effects on the solubility and mechanical properties of GG-MA were investigated. A good balance in terms of hydrophilicity and elasticity of the corresponding hydrogels was identified, although not suitable enough as injectable material for the treatment of damaged soft tissues. For this reason, several concentrations and different molecular weights of PEG-DMA were investigated to modulate the composition of GG-MA hydrogels and overcome their extreme fragility. Swelling abilities of the hydrogels in different media were studied as a key parameter able to affect the release profile of loaded therapeutic agents. Model molecules having different spherical hindrance (sulindac and vitamin B12) were then chosen to study how the hydrogels were able to modulate their diffusion profiles over time. Finally, the hydrogel's safety was evaluated trough an MTT cytotoxicity test on human fibroblasts.

Synthesis of an organic conductive porous material using starch aerogels as template for chronic invasive electrodes.

We report the development of an organic conducting mesoporous material, as coat for invasive electrodes, by a novel methodology based on the use of starch aerogel as template. The poly(3,4-ethylenedioxythiophene) (PEDOT) aerogel was synthesized by polymerization of 3,4-ethylenedioxythiophene within a saturated starch aerogel with iron (III) p-toluenesulfonate (oxidizing agent) and subsequent removal of the polysaccharide template, followed by supercritical CO2 drying. The chemical structure and oxidation state of the resulting material were studied by Raman spectroscopy. The morphology and surface properties of the obtained nanoporous material were investigated by scanning electron microscopy (SEM), micro computed tomography (µCT) and nitrogen adsorption-desorption techniques. The composition and thermal behaviour were evaluated by energy dispersive spectroscopy (EDS) and thermogravimetric analysis (TGA) respectively. A preliminary biocompatibility test verified the non-cytotoxic effects of the PEDOT aerogel. The large surface area and wide pore size distribution of the PEDOT conductive aerogel, along with its electrical properties, enable it to be used as extracellular matrix scaffold for biomedical applications.

Thermo-responsive hollow silica microgels with controlled drug release properties.

Thermo-responsive hollow silica microgels (THSMGs) consisting of a hollow core, an intermediate silica supporting layer and a smart polymer gel corona were fabricated via organic-inorganic hybridization. Hollow silica particles and PNIPAAm microgels were successfully combined by utilizing the cross-linking reaction between 3-(trimethoxysilyl) propyl methacrylate (TMSPMA) and silanol groups on the silica surface, and then the copolymerization of TMSPMA and N-isopropylacrylamide (NIPAAm). The morphology and chemical composition were systematically examined by field emission scanning electron microscope (FESEM), transmission electron microscope (TEM), energy dispersive X-ray spectroscopy (EDS) and the Brunauer-Emmett-Teller (BET) measurement. The thermo-responsive phase transition behavior was investigated by the determination of the lower critical solution temperature (LCST), and particle size measurement using dynamic light scattering. THSMGs remain porous even after the coverage of PNIPAAm gels, and also have obvious hydrophilic/hydrophobic transition property and good swelling/collapse capability in spite of the rigid silica layer. The results of in vitro cytotoxicity evaluation and Rhodamine B (RHB) release study demonstrated that THSMGs have good biocompatibility, and achieve a thermo-responsive controlled-release behavior. The prepared THSMGs show considerable potential for applications as targeted and ambient temperature responsive drug delivery system.

Nitric oxide-releasing xerogels synthesized from N-diazeniumdiolate-modified silane precursors.

Nitric oxide (NO)-releasing xerogel materials were synthesized using N-diazeniumdiolate-modified silane monomers that were subsequently co-condensed with an alkoxysilane. The NO-release characteristics were tuned by varying the aminosilane structure and concentration. The resulting materials exhibited maximum NO release totals and durations ranging from 0.45-3.2 µmol cm(-2) and 20-90 h, respectively. The stability of the xerogel networks was optimized by varying the alkoxysilane backbone identity, water to silane ratio, base catalyst concentration, reaction time, and drying conditions. The response of glucose biosensors prepared using the NO-releasing xerogel (15 mol % N-diazeniumdiolate-modified N-2-(aminoethyl)-aminopropyltrimethoxysilane) as an outer sensor membrane was linear (R(2) = 0.979) up to 24 mM glucose. The sensitivity (3.4 nA mM(-1)) of the device to glucose was maintained for 7 days in phosphate buffered saline. The facile sol-gel synthetic route, along with the NO release and glucose biosensor characteristics, demonstrates the versatility of this method for biosensor membrane applications.