Novel and effective hemostats based on graphene oxide-polymer aerogels: In vitro and in vivo evaluation.

In this study, graphene oxide (GO)-based aerogels cross-linked with chitosan (CS), gelatin (GEL), and polyvinyl alcohol (PVA) were characterized and their hemostatic efficiencies both in vitro and in vivo were investigated and compared to commercial materials (ChitoGauze®XR and Spongostan™). All aerogels exhibited highly porous structures and a negative surface charge density favorable to their interaction with blood cells. The in vitro studies showed that all aerogels coagulated >60 % of the blood contained in their structures after 240 s of the whole-blood clotting assay, the GO-CS aerogel being the one with the highest blood clotting. All aerogels showed high hemocompatibility, with hemolytic rates <5 %, indicating their use as biomaterials. Among them, the GO-GEL aerogel exhibited the lowest hemolytic activity, due possibly to its high GEL content compared to the GO amount. According to their blood clotting activity, aerogels did not promote coagulation through extrinsic and intrinsic pathways. However, their surfaces are suitable for accelerating hemostasis by promoting alternative routes. All aerogels adhered platelets and gathered RBCs on their surfaces, and in addition the GO-CS aerogel surface also promoted the formation of filamentous fibrin networks adhered on its structure. Furthermore, in vivo evaluations revealed that all aerogels significantly shortened the hemostatic times and reduced the blood loss amounts compared both to the Spongostan™ and ChitoGauze®XR commercial materials and to the gauze sponge (control group). The hemostatic performance in vitro and in vivo of these aerogels suggests that they could be used as hemostats for controlling profuse bleedings.

Improved hemocompatibility for gelatin-graphene oxide composite aerogels reinforced with proanthocyanidins for wound dressing applications.

Aerogels based on gelatin and graphene oxide (GO) were synthesized by microwave-assisted reactions, incorporating grape skin extracts -high in proanthocyanidins (PAs)- to develop a hemostatic device with improved properties. The effects of incorporating PAs into the aerogels were investigated in relation to their physicochemical properties, absorption ability, clotting activity and cytotoxicity in human dermal fibroblast (HDF) cells. The aerogels presented highly resistant porous structures, capable of absorbing more than 50 times their weight when in contact with a phosphate saline solution (PBS) and fresh human blood. Interestingly, the addition of PAs increased the negative surface charges and the blood absorption ability of the aerogels, which may make them suitable for hemostasis. The incorporation of 5% and 10% (w/w) of extracts into the aerogels increased the total coagulated blood content by 36.6% and 24.5% compared with gelatin-GO aerogel, respectively. These improvements in the hemostatic properties of the aerogels were greater with the inclusion of 5% (w/w) of grape skin extracts into the aerogels. The aerogels were also able to adhere red blood cells onto their surfaces, which could favor the formation of stable fibrin networks to promote hemostasis. Their clotting activity suggested the activation of alternative routes based on complement coagulation systems. Finally, the aerogels were non-toxic for HDF cells and the PAs were successfully released from their matrices. Thus, gelatin-GO aerogels reinforced with PAs are promising as topical phytodrug delivery systems, with great potential for wound healing processes.

Synthesis and characterization of graphene oxide chitosan aerogels reinforced with flavan-3-ols as hemostatic agents.

The natural mechanisms of the body cannot control massive hemorrhaging, resulting in a requirement for hemostatic intervention. In this study, Graphene oxide and Chitosan aerogels reinforced with grape seed (SD) and skin (SK) extracts were developed for use as hemostatic agents by evaluating the influence of pH on their synthesis, and the amount of grape extract added on the physical and chemical properties of the aerogels. The material was evaluated by FTIR, XRD, Raman spectroscopy, DLS, uniaxial compression tests and SEM. The capacity of the aerogels to absorb water, PBS and blood, as well as their coagulation capacity, were determined. In addition, the release profile for grape extracts in PBS and the material's cytotoxicity were determined. The aerogels that were synthesized under basic conditions and loaded with grape extracts were more rigid and negatively charged, and they presented smaller pores than the un-loaded acidic aerogels. For all aerogels, the hemoglobin absorption was greater than 90 % in the first 30 s. A higher density of adsorbed blood cells was observed on aerogels loaded with a higher amount of grape extract. The maximum release of extract from the aerogels occurred for those loaded with SK extracts at a basic pH; the aerogels that were prepared under acidic conditions dissolved in the media. Aerogels loaded with SK extracts under alkaline conditions were not cytotoxic toward human dermal fibroblasts and exhibited cell viabilities above 90 %. These findings suggest that these aerogels have the potential for use as hemostatic agents in wound management.

Design and Characterization of Chitosan-Graphene Oxide Nanocomposites for the Delivery of Proanthocyanidins.

INTRODUCTION: In the last years, the utilization of phytomedicines has increased given their good therapeutic activity and fewer side effects compared to allopathic medicines. However, concerns associated with the biocompatibility and toxicity of natural compounds, limit the phytochemical therapeutic action, opening the opportunity to develop new systems that will be able to effectively deliver these substances. This study has developed a nanocomposite of chitosan (CS) functionalized with graphene oxide (GO) for the delivery of proanthocyanidins (PAs), obtained from a grape seed extract (Ext.). METHODS: The GO-CS nanocomposite was covalently bonded and was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), atomic force microscopy (AFM) and by dynamic light scattering (DLS). The loading and release of Ext. from the GO-CS nanocomposite were performed in simulated physiological, and the cytotoxicity of the raw materials (GO and Ext.) and nanocomposites (GO-CS and GO-CS-Ext.) was determined using a human kidney cell line (HEK 293). RESULTS: The chemical characterization indicated that the covalent union was successfully achieved between the GO and CS, with 44 wt. % CS in the nanocomposite. The GO-CS nanocomposite was thermostable and presented an average diameter of 480 nm (by DLS). The Ext. loading capacity was approximately 20 wt. %, and under simulated physiological conditions, 28.4 wt.% Ext. (g) was released per g of the nanocomposite. GO-CS-Ext. was noncytotoxic, presenting a 97% survival rate compared with 11% for the raw extract and 48% for the GO-CS nanocomposite at a concentration of 500 µg mL-1 after 24 hrs. CONCLUSION: Due to π-π stacking and hydrophilic interactions, GO-CS was reasonably efficient in binding Ext., with high loading capacity and Ext. release from the nanocomposite. The GO-CS nanocomposite also increased the biocompatibility of PAs-rich Ext., representing a new platform for the sustained release of phytodrugs.

Development of Graphene Oxide Composite Aerogel with Proanthocyanidins with Hemostatic Properties As a Delivery System.

The graphene aerogels' potential for use as both a hemostatic agent and dermal delivery system has scarcely been investigated. In this study, we used a sol-gel process for generating dry and stable composite aerogels based on graphene oxide (GO) and poly(vinyl alcohol) (PVA). Furthermore, we incorporated natural extract of País grape seed (SD) and skin (SK), rich in proanthocyanidins (PAs or condensed tannins). The effect of the incorporation of the grape extracts was investigated in relation to the aerogels' structure, coagulation performance and the release of the extracts. The results demonstrated that they have a porous structure and low density, capable of absorbing water and blood. The incorporation of 12% (w/w) of PA extracts into the aerogel increased the negative zeta potential of the material by 33% (-18.3 ± 1.3 mV), and the coagulation time was reduced by 37% and 28% during the first 30 and 60 s of contact between the aerogel and whole blood, respectively. The release of extracts from the GO-PVA-SD and GO-PVA-SK aerogels was prolonged to 3 h with 20%, probably due to the existence of strong binding between PAs andGO-PVA, both characterized by the presence of aromatic and hydroxyl groups that can form noncovalent bonds but are strong and stable enough to avoid a greater release into the medium. This study provides a new GO-based aerogel, which has a great potential use in the field of dermal delivery, wound healing and/or the treatment of trauma bleeding.

Causas de consultas e internamientos de niños en el Hospital Infantil Dr. Robert Reid Cabral / Causer of consult and admission at the \"Dr. Robert Reid Cabral\" Children's Hospital

Con el propósito de conocer las causas, tanto de consultas como de internacmientos, de las que demandan atención médica en el hospital Infantil Dr. Robert Read Cabral, se realizó un estudio que abarcó 360 niños escogidos al azar durante el período comprendido entre julio de 1989 y junio de 1990. La mayoría de los niños estudiados, tanto en el área externa como hospitalizados, correspondió a menores del año (59.4//), al sexo masculino (62.2//) y procedían de las zonas urbanas (73.6//). Las infecciones respiratorias agudas (22.5//), la enfermedad diarreica aguda (15.0//) y las parasitosis (8.3//) fueron las causas mas comunes de demandas de atención en el área externa. En cambio, la EDA (5.0//), las neumonías (2.8//), los traumatismos (2.8//) y los estados mórbidos secundarios, muchos de ellos a la EDA e IRA, conocidos como sepsis (2.5//), las causas más importante de admisiones hospitalarias

Causas de consultas e internamiento de niños: Hospital Infantil Robert Reid Cabral (1989-1990) / Consults and admission of children : Hospital Infantil Robert Reid Cabral (1989-1990)

Con el propósito de conocer las causas, tanto de consultas como de internamientos de quienes demandadn atención médica en el hospital infantil Robert Reid Cabral, Santo Domingo, República Dominicana, se realizó un estudio que abarcó 360 niños escogidos al azar durante el período comprendido entre julio de 1989 y junio de 1990. La mayoría de los niños estudiados, tanto en el área externa como hospitalizados, correpondió a menores de un año (59.4 por ciento ), al sexo masculino (62.2 por ciento ) y procedían de las zonas urbanas (73.6 por ciento ). Las infecciones respiratorias agudas (22.5 por ciento ), la enfermedad diarréica aguda (25.0 por ciento ) y las parasitoris (8.3 por ciento ) fueron las causas más comunes de demanda de atención en el área externa. En cambio, la EDA (5.0 por ciento ), las neumonías (2.8 por ciento ), los traumatismos (2.8 por ciento ) y los estados mórbidos secundarios, muchos de ellos a la EDA e IRA, conocidos como sepsis (2.5 por ciento ), fueron las causas más importantes de admisiones hospitalarias