Self-expanding cellulose sponge with enhanced hemostatic ability by tannic acid/metal ion composite coating for highly effective hemostasis of difficult-to-control bleeding wounds.

Refractory bleeding presents a critical, life-threatening challenge, and the goal of medical professionals and researchers has always been to achieve safe and effective hemostasis for bleeding wounds. In this study, we utilized the benefits of a self-expanding cellulose sponge to control incompressible bleeding, which is achieved this by creating a tannic acid/metal ion coating on the surface and within the pores of the sponge to improve its hemostatic effectiveness. The effects of various types and concentrations of metal ions (calcium, magnesium, iron, and zinc) on hemostatic efficiency and biosafety is systematically investigated. The results from bacteriostasis and in vitro coagulation experiments identified 0.3 wt% Fe3+ as the optimal metal ion coating. Scanning electron microscope energy spectrum analysis confirmed the uniform distribution of Fe3+ within the cellulose sponge. Furthermore, the in vivo and in vitro results demonstrated that the prepared tannic acid/Fe3+ coated composite hemostatic sponge exhibits excellent coagulation ability and biocompatibility. Both the bleeding time and theblood loss in two bleeding models are significantly reduced, showing promising potential for treating extensive surface bleeding and deep penetrating wounds. Furthermore, the straightforward preparation method for this composite hemostatic sponge facilitates additional research towards market application.

Study on chitosan/gelatin hydrogels containing ceria nanoparticles for promoting the healing of diabetic wound.

Chronic inflammation at diabetic wound sites results in the uncontrolled accumulation of pro-inflammatory factors and reactive oxygen species (ROS), which impedes cell proliferation and delays wound healing. To promote the healing of diabetic wounds, chitosan/gelatin hydrogels containing ceria nanoparticles (CNPs) of various sizes were created in the current study. CNPs' efficacy in removing O 2 • - , •OH, and H2O2 was demonstrated, and the scavenging ability of CNPs of varying sizes was compared. The in vitro experiments demonstrated that hydrogels containing CNPs could effectively protect cells from ROS-induced damage and facilitate mouse fibroblast migration. Furthermore, during the treatment of diabetic wounds in vivo, hydrogels containing CNPs exhibited anti-inflammatory activity and could reduce the expression of the pro-inflammatory factors TNF-α (above 30%), IL-6 (above 90%), and IL-1ß (above 80%), and effectively promote wound closure (above 80%) by inducing re-epithelialization, collagen deposition, and angiogenesis. In addition, the biological properties and therapeutic effects of hydrogels containing CNPs of various sizes were compared and discussed. The finding revealed that hydrogels with 4 nm CNPs exhibited more significant biological properties and had implications for diabetic wound treatment.

Protective effect of ethyl ferulate against hypoxic injury in retinal cells and retinal neovascularization in an oxygen-induced retinopathy model.

BACKGROUND: Pathological neovascularization is a major cause of visual impairment in hypoxia-induced retinopathy. Ethyl ferulate (EF), the natural ester derivative of ferulic acid commonly found in Ferula and Angelica Sinensis, has been shown to exert antioxidant, neuroprotective, and anti-inflammatory properties. However, whether EF exerts a protective effect on retinal neovascularization and the underlying mechanisms are not well known. PURPOSE: The aim of the study was to investigate the effect of EF on retinal neovascularization and explore its underlying molecular mechanisms. STUDY-DESIGN/METHODS: We constructed hypoxia models induced by cobalt chloride (CoCl2) in ARPE-19 cells and Rhesus choroid-retinal vascular endothelial (RF/6A) cells in vitro, as well as a retinal neovascularization model in oxygen-induced retinopathy (OIR) mice in vivo. RESULTS: In this work, we demonstrated that EF treatment inhibited hypoxia-induced vascular endothelial growth factor A (VEGFA) expression in ARPE-19 cells and abrogated hypoxia-induced tube formation in RF/6A cells. As expected, intravitreal injection of EF significantly suppressed retinal neovascularization in a dose-dependent manner in OIR retinas. We also found that hypoxia increased VEGFA expression by blocking autophagic flux, whereas EF treatment enhanced autophagic flux, thereby reducing VEGFA expression. Furthermore, EF activated the sequestosome 1 (p62) / nuclear factor E2-related factor 2 (Nrf-2) pathway via upregulating oxidative stress-induced growth inhibitor 1 (OSGIN1) expression, thus alleviating oxidative stress and reducing VEGFA expression. CONCLUSION: As a result of our findings, EF has an inhibitory effect on retinal neovascularization, implying a potential therapeutic strategy for hypoxia-induced retinopathy.

Morphology-controllable cellulose/chitosan sponge for deep wound hemostasis with surfactant and pore-foaming agent.

Developing a facile and scalable synthetic route is important to explore the potential application of functional cellulose sponges. Here, a simple and efficient strategy to produce porous and hydrophilic cellulose sponges using surfactant and pore-foaming agent is demonstrated. The obtained cellulose sponges exhibit high water absorption capacity and rapid shape recoverability. The introduction of chitosan endows the chitosan/cellulose composite sponge with good mechanical properties. Inhibitory effects on Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa are particularly proved. Besides, the result of the dynamic whole blood clotting time indicated that the chitosan/cellulose composite sponge has better coagulation ability than those of traditional gauze and gelatin sponge. Animal experiment further showed that rapid hemostasis within 105 s could be reached with the composite sponge. Good biocompatibility of the composite sponge is proved by the results of hemocompatibility and cytotoxicity, indicating an excellent candidate as a rapid hemostatic material.

Rapid hemostatic chitosan/cellulose composite sponge by alkali/urea method for massive haemorrhage.

Here, a simple and efficient strategy to produce porous and hydrophilic chitosan/cellulose sponge using surfactant and pore-forming agent is demonstrated. The preparation of composite sponge by LiOH/KOH/urea solvent system effectively solve the problems of uneven distribution of chitosan, poor softness and acid residue caused by soaking in chitosan acid solution. The obtained chitosan/cellulose sponges exhibit high water absorption capacity and rapid shape recoverability, as well as good mechanical properties. Effective inhibitory on Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa are particularly proved. Besides, the result of the dynamic whole blood clotting time indicated that the chitosan/cellulose composite sponge has better coagulation ability than those of traditional gauze and gelatin sponge. Animal experiment further showed that rapid hemostasis within 34 s can be reached with the composite sponge. Better biocompatibility of the composite sponge is proved by the results of hemocompatibility and cytotoxicity, indicating an excellent candidate for rapid hemostasis in massive haemorrhage.

One-step fabrication of chitosan sponge and its potential for rapid hemostasis in deep trauma.

In this paper, a facile and efficient preparation strategy for a porous and hydrophilic chitosan sponge is demonstrated, combining a surfactant and a pore-foaming agent. The resulting chitosan sponge possesses an interconnected pore structure and soft texture, exhibits fast water absorption rate and capacity, and the compressed sponge can achieve full shape recovery 5 s after absorbing water. Moreover, our process removes the residual acid commonly found in chitosan sponges prepared by the acid method. In addition, the results demonstrate the useful characteristics of our chitosan sponge, in terms of its contribution to improved blood coagulation, together with its compression strength and biocompatibility. It also demonstrates effective antibacterial properties in relation to both Escherichia coli and Staphylococcus aureus. Further testing via animal experimentation reveals that rapid hemostasis can be achieved within 50 s using our chitosan sponge.

Injectable antibacterial cellulose nanofiber/chitosan aerogel with rapid shape recovery for noncompressible hemorrhage.

Here an injectable antibacterial aerogel was fabricated with oxidized cellulose nanofiber and chitosan for rapid hemostasis of noncompressible hemorrhage application. Especially, cellulose nanofiber was modified with carboxyl groups by pre-oxidizing in 2,2,6,6-tetramethylpiperidine-1-oxyl combined with high pressure homogenization. Whereafter, the realized carboxyl group of cellulose nanofiber was reacted with the amidogen of chitosan to yield a strong composite aerogel with a nanofiber/nanosheet interlaced structure, which increased the compressive mechanical strength up to 75.4 kPa. In addition, the nanocellulose/chitosan composite aerogel exhibits high water absorption capacity, rapid shape recovery and good antibacterial ability (via Escherichia coli and Staphylococcus aureus). Once absorbing water, the nanocellulose5/chitosan5 compressed aerogel could rapidly recover its shape within 30 s. The in vitro coagulation ability measurement showed that the composite aerogel has a good adhesion and aggregation effect to red blood cells and platelets. Hemolysis and cytotoxicity analysis results indicated a good biocompatibility for the composite aerogel.

Incorporation of microfibrillated cellulose into collagen-hydroxyapatite scaffold for bone tissue engineering.

In this study, the composite of Collagen-Hydroxyapitite (COL-HA) with microfibrillated cellulose (MFC) was developed as a new bone substitute material. COL-HA was prepared by in-situ method and modified by dehydrothermal treatment. Microfibrillated cellulose (MFC), a nature polysaccharide with plenty of hydroxyl groups, was incorporated into COL-HA composites to improve the properties. The novel COL-HA-MFC scaffold with different ratios of COL-HA and MFC were fabricated by cold isostatic pressing technique and freeze-drying technology. During the forming process, a three-dimensional bone-like structure was shaped in hybrid scaffolds. The microstructural transitions of COL-HA-MFC composites were examined by Fourier transform infrared spectroscope (FTIR), Ultraviolet-visible spectrophotometer (UV), and X-ray diffraction (XRD), which indicated that HA deposited on collagen molecules and MFC bonded with COL-HA. Hydrophilicity, swelling property, mechanical property, and degradability of COL-HA-MFC composites were investigated. Biological properties, such as cytotoxicity and hemolysis, were also studied. The results showed a good swelling capacity for the scaffolds, keeping their original shapes after swelling. The compression strength and degradability of the scaffold materials could be regulated by the MFC content. The compression strength of COL-HA-MFC composite scaffords increased to 20-40 MPa, closing to that of the nature bone (1-200 MPa). The obtained scaffolds are good in biocompatibility with high level of cell growth rate (>70%) and suitable hemolysis rate (≦5%). The work might provide an efficient and alternative approach for collagen-based biomaterials with necessary properties. The COL-HA-MFC composite scaffold showed a potential application in bone tissue engineering.

Morphology-Controllable Collagen/Poly(2-hydroxyethyl methacrylate) Porous Hydrogel with a Paraffin Microsphere as a Template.

In this study, a porous poly(2-hydroxyethyl methacrylate) (PHEMA) matrix was fabricated by a paraffin template method, which was used as a substrate to adhere collagen fibers to form an interconnective porous collagen/PHEMA (Col-PHEMA) composite hydrogel. A microscope and scanning electron microscope (SEM) were employed to characterize the morphology of paraffin microspheres and Col-PHEMA composite hydrogels. The paraffin microspheres with the diameter in the range from 100 to 200 µm were collected by a preset sieve. Then, the interface of uniform paraffin microspheres were thermally bonded to form a contacted template, and the derived Col-PHEMA composite hydrogels had an interconnective porous microstructure. Fourier transform infrared spectroscopy (FTIR) indicated that new hydrogen bonds were formed between collagen fibers and the PHEMA hydrogel. Besides, the Col-PHEMA composite hydrogels revealed a high hydrophilicity, good mechanical properties, and good water uptake capacity. The porous Col-PHEMA composite hydrogels showed a good biocompatibility, and the collagen layer may promote the proliferation of fibroblast cells. The Col-PHEMA composite hydrogel is expected to find an application in corneal repairing.

Nano-TiO2/collagen-chitosan porous scaffold for wound repairing.

Collagen-Chitosan (COL-CS) porous scaffolds have been widely used as a dermal equivalent to induce fibroblasts infiltration and dermal regeneration. To improve the anti-bacterial properties, nano-TiO2 hydrosol was introduced into COL-CS scaffolds. TiO2/COL-CS porous scaffolds were fabricated through a freeze-drying process, and scanning electron microscopy (SEM) was employed to study the micro-structure of the scaffolds. Fourier transform infrared spectroscopy (FT-IR) was used to study the intermolecular interactions in the scaffolds. The swelling property, porosity, degradation, antibacterial behavior, red blood cell aggregation, and cytotoxicity of the composite were investigated. The results showed that the scaffold is good in permeability and it may provide a humid environment for wound repairing. The degradation in lysozyme solution for 4 weeks showed that porous scaffolds are good in stability, which may satisfy the wound coverage protection in the repairing period. An obvious inhibitory effect on Staphylococcus aureus of the porous scaffolds was found, and the red blood cells were easy to form clusters aggregation to stop bleeding. It was suggested that the TiO2/COL-CS composite scaffolds could be a promising candidate for wound repairing dressing.

Nanocomposite scaffold with enhanced stability by hydrogen bonds between collagen, polyvinyl pyrrolidone and titanium dioxide.

In this study, three-dimensional (3D) nanocomposite scaffolds, as potential substrates for skin tissue engineering, were fabricated by freeze drying the mixture of type I collagen extracted from porcine skin and polyvinyl pyrrolidone (PVP)-coated titanium dioxide (TiO2) nanoparticles. This procedure was performed without any cross-linker or toxic reagents to generate porosity in the scaffold. Both morphology and thermal stability of the nanocomposite scaffold were examined. The swelling behavior, mechanical properties and hydrolytic degradation of the composite scaffolds were carefully investigated. Our results revealed that collagen, PVP and TiO2 are bonded together by four main hydrogen bonds, which is an essential action for the formation of nanocomposite scaffold. Using Coasts-Redfern model, we were able to calculate the thermal degradation apparent activation energy and demonstrated that the thermal stability of nanocomposites is dependent on amount of PVP incorporated. Furthermore, SEM images showed that the collagen fibers are wrapped and stabilized on scaffolds by PVP molecules, which improve the ultimate tensile strength (UTS). The UTS of PVP-contained scaffold is four times higher than that of scaffold without PVP, whereas ultimate percentage of elongation (UPE) is decreased, and PVP can enhance the degradation resistance.