Multifunctional Casein-Based Wound Dressing Capable of Monitoring and Moderating the Proteolytic Activity of Chronic Wounds.

Every 1.2 s, a diabetic foot ulcer is developed, and every 20 s, one amputation is carried out in diabetic patients. Monitoring and controlling protease activity have been considered as a strategy for more efficient management of diabetic and other chronic wounds. This study aimed to develop a casein-based dressing that, by its disappearance, provides information about the activity of proteases and simultaneously harnesses proteolytic activity. Casein films were fabricated by using an aqueous solution, and heat treatment was successfully deployed as a green and clean approach to confer hydrolytic stability. Our results showed that casein-based films' mechanical characteristics, water absorption, and proteolytic stability could be controlled by the length of the heat treatment, which proved to be a useful tool. An increase in the treatment duration from 30 min to 3 h led to toleration of 2.4 times higher stress, 2 times lower water uptake, and 3.4 times higher proteolytic stability at examined conditions. Selected casein-based structures responded to Bacillus sp. bacteria's protease (BSP) and human neutrophil elastase (HNE) as representatives of bacterial and nonbacterial proteases found in the wounds at 10 and 200 ng mL-1 levels, respectively. The hydrolysis was accompanied by a 36% reduction in proteolytic activity measured by using a casein-based universal protease activity assay. The released casein fragments could scavenge 90% of the examined radicals. In-vitro cell culture studies showed that the hydrolysates were not cytotoxic, and the casein-based film had a favorable interaction with fibroblast cells, indicating its potential as a scaffold in the case that proteolytic activity would not be to the extent that causes its rapid disintegration. In general, these findings hold promise for applying the developed casein-based structure for detecting proteolytic activity without the need for any equipment, kits, or expertise and, more importantly, in a highly economical manner. In the case that the proteolytic activity would not be severe, it could also serve as a substrate for cell adhesion and growth; this would aid in the healing process.

Insight into the nanostructure of anisotropic cellulose aerogels upon compression.

Cellulose II aerogels are a highly porous class of biobased ultra-light-weight materials. They consist of interlinked networks of loosely aggregated cellulose fibrils. The latter typically have random orientation due to spontaneous phase separation triggered by addition of antisolvent to moleculardisperse cellulose solutions. Deceleration of phase separation has been recently proposed as a novel approach towards aerogels featuring preferred cellulose orientation. Here, we investigate the mechanical response of such oriented cellulose aerogels towards load up to 80% compression. Stress-strain curves were recorded and in situ small angle X-ray scattering (SAXS) was performed during compression test to obtain information about the structural alterations of the aerogel fibril networks on the nano-scale related to deformation. Using SAXS in addition, structural changes can be followed in much more detail than by recording stress-strain curves alone. Buckling and coalescence of fibers and a change in fibril orientation can be related to certain regimes in the stress-strain curve. If the loading axis is oriented parallel to the network orientation the aerogels show higher resilience towards the compression.

Anisotropic nanocellulose gel-membranes for drug delivery: Tailoring structure and interface by sequential periodate-chlorite oxidation.

This study investigates periodate-chlorite oxidation as a pretreatment to tailor the surface charge density of cellulose nanofibers employed in open-porous anisotropic hydrogel membranes for transdermal drug delivery. The obtained materials feature high specific surface (≤500 m2 g-1, BET), small average pore size (ca. 40 nm) and tunable surface charge, which are key properties for adsorption and slow release of charged drug molecules. Loading of the non-steroidal anti-inflammatory drug (NSAID) piroxicam (PRX) into the membranes confirmed that the extent of loading is governed by surface charge density and carboxylate group content, respectively, which can be controlled by the oxidation procedure within the range of 0.74-2.00 mmol g-1. Prolonged release of PRX over several hours was observed upon exposure of the loaded membranes to simulated human skin fluid demonstrating the applicability as drug delivery patches.

Self-Assembly of Cellulose in Super-Cooled Ionic Liquid under the Impact of Decelerated Antisolvent Infusion: An Approach toward Anisotropic Gels and Aerogels.

Assembly of (bio)polymers into long-range anisotropic nanostructured gels and aerogels is of great interest in advanced material engineering since it enables directional tuning of properties, such as diffusivity, light, heat, and sound propagation, cell proliferation, and mechanical properties. Here we present an approach toward anisotropic cellulose II gels and aerogels that employs specific diffusion and phase separation phenomena occurring during decelerated infusion of an antisolvent into isotropic supercooled solutions of cellulose in an ionic liquid to effectuate supramolecular assembly of cellulose in anisotropic colloidal network structures. At the example of the distillable ionic liquid 1,1,3,3-tetramethylguanidinium acetate, the antisolvent ethanol, and spherocylindrical porous molds, we demonstrate that the proposed facile, environmental-benign and versatile route affords gels and aerogels whose specific anisotropic nanomorphology and properties reflect the preferred supramolecular cellulose orientation during phase separation, which is perpendicular to the direction of antisolvent diffusion. Comprehensive X-ray scattering experiments revealed that the (aero)gels are composed of an interconnected, fibrous, highly crystalline (CrI ≈ 72%), cellulose II with a cross-sectional Guinier radius of the struts of about 2.5 nm, and an order parameter gradient from about 0.1 to 0.2. The obtained gels and aerogels feature high specific surface areas (350-630 m2 g-1) and excellent mechanical properties like high toughness (up to 471 kJ m-3 for a 60% compression, ρB = 80 mg cm-3) and resilience (up to 13.4 kJ m-3, ρB = 65 mg cm-3).

Transparent, Flexible, and Strong 2,3-Dialdehyde Cellulose Films with High Oxygen Barrier Properties.

2,3-Dialdehyde cellulose (DAC) of a high degree of oxidation (92% relative to AGU units) prepared by oxidation of microcrystalline cellulose with sodium periodate (48 °C, 19 h) is soluble in hot water. Solution casting, slow air drying, hot pressing, and reinforcement by cellulose nanocrystals afforded films (∼100 µm thickness) that feature intriguing properties: they have very smooth surfaces (SEM), are highly flexible, and have good light transmittance for both the visible and near-infrared range (89-91%), high tensile strength (81-122 MPa), and modulus of elasticity (3.4-4.0 GPa) depending on hydration state and respective water content. The extraordinarily low oxygen permeation of <0.005 cm3 µm m-2 day-1 kPa-1 (50% RH) and <0.03 cm3 µm m-2 day-1 kPa-1 (80% RH) can be regarded as a particularly interesting feature of DAC films. The unusually high initial contact angle of about 67° revealed a rather low hydrophilicity compared to other oxidatively modified or unmodified cellulosic materials which is most likely the result of inter- and intramolecular hemiacetal and hemialdal formation during drying and pressing.