Drug-impregnated, pressurized gas expanded liquid-processed alginate hydrogel scaffolds for accelerated burn wound healing.

While the benefits of both hydrogels and drug delivery to enhance wound healing have been demonstrated, the highly hydrophilic nature of hydrogels creates challenges with respect to the effective loading and delivery of hydrophobic drugs beneficial to wound healing. Herein, we utilize pressurized gas expanded liquid (PGX) technology to produce very high surface area (~200 m2/g) alginate scaffolds and describe a method for loading the scaffolds with ibuprofen (via adsorptive precipitation) and crosslinking them (via calcium chelation) to create a hydrogel suitable for wound treatment and hydrophobic drug delivery. The high surface area of the PGX-processed alginate scaffold facilitates >8 wt% loading of ibuprofen into the scaffold and controlled in vitro ibuprofen release over 12-24 h. In vivo burn wound healing assays demonstrate significantly accelerated healing with ibuprofen-loaded PGX-alginate/calcium scaffolds relative to both hydrogel-only and untreated controls, demonstrating the combined benefits of ibuprofen delivery to suppress inflammation as well as the capacity of the PGX-alginate/calcium hydrogel to maintain wound hydration and facilitate continuous calcium release to the wound. The use of PGX technology to produce highly porous scaffolds with increased surface areas, followed by adsorptive precipitation of a hydrophobic drug onto the scaffolds, offers a highly scalable method of creating medicated wound dressings with high drug loadings. STATEMENT OF SIGNIFICANCE: While medicated hydrogel-based wound dressings offer clear advantages in accelerating wound healing, the inherent incompatibility between conventional hydrogels and many poorly water-soluble drugs of relevance in wound healing remains a challenge. Herein, we leveraged supercritical fluids-based strategies to both process and subsequently impregnate alginate, followed by post-crosslinking to form a hydrogel, to create a very high surface area alginate hydrogel scaffold loaded with high hydrophobic drug contents (here, >8 wt% ibuprofen) without the need for any pore-forming additives. The impregnated scaffolds significantly accelerated burn wound healing while also promoting regeneration of the native skin morphology. We anticipate this approach can be leveraged to load clinically-relevant and highly bioavailable dosages of hydrophobic drugs in hydrogels for a broad range of potential applications.

Characterization of oat beta-glucan and coenzyme Q10-loaded beta-glucan powders generated by the pressurized gas-expanded liquid (PGX) technology.

The physicochemical properties of the oat beta-glucan powder (BG) and coenzyme Q10 (CoQ10)-loaded BG powder (L-BG) produced by the pressurized gas-expanded liquid (PGX) technology were studied. Helium ion microscope, differential scanning calorimeter, X-ray diffractometer, AutoSorb iQ and rheometer were used to determine the particle morphology, thermal properties, crystallinity, surface area and viscosity, respectively. Both BG (7.7µm) and L-BG (6.1µm) were produced as micrometer-scale particles, while CoQ10 nanoparticles (92nm) were adsorbed on the porous structure of L-BG. CoQ10 was successfully loaded onto BG using the PGX process via adsorptive precipitation mainly in its amorphous form. Viscosity of BG and L-BG solutions (0.15%, 0.2%, 0.3% w/v) displayed Newtonian behavior with increasing shear rate but decreased with temperature. Detailed characterization of the physicochemical properties of combination ingredients like L-BG will lead to the development of novel functional food and natural health product applications.

Design of a high-pressure circulating pump for viscous liquids.

The design of a reciprocating dual action piston pump capable of circulating viscous fluids at pressures of up to 34 MPa (5000 psi) and temperatures up to 80 degrees C is described. The piston of this pump is driven by a pair of solenoids energized alternatively by a 12 V direct current power supply controlled by an electronic controller facilitating continuously adjustable flow rates. The body of this seal-less pump is constructed using off-the-shelf parts eliminating the need for custom made parts. Both the electronic controller and the pump can be assembled relatively easily. Pump performance has been evaluated at room temperature (22 degrees C) and atmospheric pressure using liquids with low and moderately high viscosities, such as ethanol and corn oil, respectively. At ambient conditions, the pump delivered continuous flow of ethanol and corn oil at a flow rate of up to 170 and 17 cm3/min, respectively. For pumping viscous fluids comparable to corn oil, an optimum reciprocation frequency was ascertained to maximize flow rate. For low viscosity liquids such as ethanol, a linear relationship between the flow rate and reciprocation frequency was determined up to the maximum reciprocation frequency of the pump. Since its fabrication, the pump has been used in our laboratory for circulating triglycerides in contact with supercritical carbon dioxide at pressures of up to 25 MPa (3600 psi) and temperatures up to 70 degrees C on a daily basis for a total of more than 1500 h of operation functioning trouble free.