Addition of 2-deoxy-d-ribose to clinically used alginate dressings stimulates angiogenesis and accelerates wound healing in diabetic rats

Abstract

Following recent work from our group on a small ribose-derived sugar 2-deoxy-d-ribose which stimulates angiogenesis in a chick chorionic allantoic membrane bioassay and in skin wounds in healthy rats, we tested the effect of this sugar when added to a common alginate wound dressing in a well-accepted diabetic skin wound model in rats. Dressings were simply loaded with filter-sterilized sugar solutions that were proved stable at room temperature for at least two weeks. Prior to undertaking the animal study, we assessed in vitro release of sugar loaded from alginate dressings loaded with either 5 or 10% 2-deoxy-d-ribose. Both showed more than 90% release of sugar over three days followed by a lesser and sustained release for up to eight days. Diabetes was induced in rats by streptozotocin injection followed by confirmation through measuring elevated blood glucose levels all over the period of the study. Full thickness skin wounds of 20 mm diameter showed slow healing and were still unhealed at 20th day in the control animals. The addition of alginate hydrogel did significantly stimulate wound healing compared to the untreated animals, but the addition of 2-deoxy-d-ribose at either 5 or 10% further and significantly improved the rate of wound healing. The most striking result was seen in the effect of sugar on angiogenesis in the wound beds where alginate alone did not improve the extent of CD34 identified blood vessels in the wound beds but the addition of sugar significantly increased these – this could be seen as early as seven days post addition of the sugar-loaded alginate dressing and was still evident at day 20. Thus, these results suggest that the controlled use of 2-deoxy-d-ribose could be a novel and cost-effective therapy for the management of impaired wound healing in diabetic patients.

Assessment of the Angiogenic Potential of 2-Deoxy-D-Ribose Using a Novel in vitro 3D Dynamic Model in Comparison With Established in vitro Assays

“…2dDR is a promising pro-angiogenic alternative which has been reported to have chemotactic and angiogenic activity by our group and other researchers using a range of current angiogenic assays: Boyden chamber assay (Uchimiya et al, 2002), tube formation assay (Uchimiya et al, 2002), CAM assay (Haraguchi et al, 1994;Dikici et al, 2019b), and rat wound healing models (Yar et al, 2017;Azam et al, 2019). However, the dose-dependent response to 2dDR still remains to be investigated in vitro to determine what is the effective concentration range to drive angiogenesis at the cellular level.…”

“…2dDR has previously demonstrated to have chemotactic and angiogenic activity in vivo (Haraguchi et al, 1994;Matsushita et al, 1999). Similarly, our group recently demonstrated the angiogenic potential of 2-deoxy-D-ribose (2dDR) using an ex-ovo CAM assay (Dikici et al, 2019b) and a diabetic rat model (Azam et al, 2019). Several groups evaluated the angiogenic activity of 2dDR in vitro but only using a narrow range of concentrations.…”

<p>Oxygen Generating Polymeric Nano Fibers That Stimulate Angiogenesis and Show Efficient Wound Healing in a Diabetic Wound Model</p>

“…Wound closure (%) was calculated on days 3, 7, 14, 21, and 27 after implantation of the mats, using a given formula 23 by using image J software (Image J version 1.52a). For this purpose, high resolution images of wounds of all rats were captured at a uniform magnification.…”

Use of hypertonic glucose (10%) in the prevention of postoperative adhesions in rats

“…These materials increase the cost of surgery and have unreliable effects in the prevention of adhesions 2 , 6 . Several other substances with different mechanisms of action, such as cow peritoneum, amniotic membranes or liquids, oxidized celluloses, olive oil, soybean oil, starch, glycerol, honey, diluted glucose, corticosteroids, and many others have been tried to prevent the formation of postoperative peritoneal adhesion 2 , 6 – 8 , 12 , 13 , 22 , 25 .…”