An alginate-Based tube gel delivering 2-deoxy-D-ribose for stimulation of wound healing

Abstract

Developing multifunctional wound dressings capable of inducing rapid angiogenesis and with antibacterial activity would be attractive for diabetic and superficial wound healing. Hydrogels delivered from tubes have several desirable features -they are easy to apply, keep the wound moist, reduce the entry of microorganisms and avoid the need for painful dressing removal. Previously we reported that 2 deoxy-D-ribose (2dDR) delivered from a variety of dressings is capable of promoting wound healing by stimulating angiogenesis. Alginate hydrogels are an ideal vehicle to deliver a bioactive agent capable of promoting wound healing. In this study we developed and evaluated a tube hydrogel capable of delivering 2dDR with the aim of achieving a stable, convenient to administer and biologically effective wound treatment. Further, we included the stabilizer 2-phenoxy ethanol which provided antimicrobial activity. We synthesized hydrogels by the Green method, using simple mixing of sodium alginate, propylene glycol, 2-phenoxy ethanol and 2dDR in water. FTIR (Fourier transformation infrared spectroscopy) analysis confirmed an absence of undesirable chemical changes in the gel components, and SEM images of the freeze-dried gels showed porous structures. When 2dDR alginate gel (2dDR-SA hydrogel) was placed in PBS at 37°C, almost 92% of 2dDR was released within 7 days. When tested on cultured cells, 2dDR-SA hydrogels did not inhibit metabolic activity or proliferation, achieving up to 90 and 98% of control respectively over 7 days. 2dDR-SA hydrogel also showed anti-bacterial activity against E. coli, Pseudomonas aeruginosa, Staphylococcus aureus, and MRSA which was attributable to the stabilizer 2-phenoxy ethanol in the hydrogel. Stimulation of angiogenesis in the chorioallantoic membrane assay by 2dDR-SA hydrogel was found to be significant compared to the blank-SA. Wound healing potential was studied in full-thickness wounds in rats where acceleration of wound healing was seen. H&E staining of the wound tissue showed an enhanced number of blood vessels and re-epithelization, and a reduced number of inflammatory cells in 2dDR-SA treated animals compared to blank-hydrogels while Masson’s trichrome staining showed increased collagen deposition. In summary we describe a convenient to apply hydrogel which has promise for use in a range of superficial skin wounds including applications in chronic wound care.

Graphical Abstract

Keywords

2dDR-SA hydrogel chorio-allantoic membrane assay Cell metabolic activity proliferation re-epithelization inflammatory cells collagen deposition

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