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. 2020 Aug:112:101-111.
doi: 10.1016/j.actbio.2020.06.006. Epub 2020 Jun 6.

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

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

Kelli-Anne Johnson et al. Acta Biomater. 2020 Aug.

Abstract

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.

Keywords: Alginate; Drug delivery; Hydrogels; Ibuprofen; Supercritical fluids; Wound healing.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Moquin and Seifried (co-authors) are employees of Ceapro Inc., which holds the patent for pressurized gas expanded liquids (PGX) process used to produce the highly porous alginate scaffold for this work. In addition, while the grant sponsoring this work is fully funded financially by the Natural Sciences and Engineering Research Council of Canada (NSERC), Ceapro (through Moquin, VP Research) has provided substantial in-kind support to this research in terms of access to equipment as well as staff time. Aside from this grant, however, there is no other financial relationship between the PI and Ceapro. In addition, while the company did review the paper prior to submission to ensure acceptable disclosure of details around the PGX process, there was no other influence by the company on the results or conclusions presented.

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