Nano-formulated curcumin accelerates acute wound healing through Dkk-1-mediated fibroblast mobilization and MCP-1-mediated anti-inflammation

Xinyi Dai,Juan Liu,Arndt F Schilling,Carina Prein,Ursula Hopfner,Hans-Günther Machens,Johannes Wichmann,Huaiyuan Zheng,Yi Shen,Stefanie Sudhop

doi:10.1038/am.2017.31

Abstract

Turmeric, a product of Curcuma longa, has a very long history of being used for the treatment of wounds in many Asian countries. Curcumin, the principal curcuminoid of turmeric, has recently been identified as a main mediator of turmeric’s medicinal properties. However, the inherent limitations of the compound itself, such as hydrophobicity, instability, poor absorption and rapid systemic elimination, pose big hurdles for translation to wider clinical application. We present here an approach for engineering curcumin/gelatin-blended nanofibrous mats (NMs) by electrospinning to adequately enhance the bioavailability of the hydrophobic curcumin for wound repair. Curcumin was successfully formulated as an amorphous nanosolid dispersion and favorably released from gelatin-based biomimetic NMs that could be easily applied topically to experimental wounds. We show synergistic signaling by the released curcumin during the healing process: (i) mobilization of wound site fibroblasts by activating the Wnt signaling pathway, partly mediated through Dickkopf-related protein-1, and (ii) persistent inhibition of the inflammatory response through decreased expression of monocyte chemoattractant protein-1 by fibroblasts. With a combination of these effects, the curcumin/gelatin-blended NMs enhanced the regenerative process in a rat model of acute wounds, providing a method for translating this ancient medicine for use in modern wound therapy.

Highlights

Severe acute wounds, as a result of trauma or surgery, are estimated to affect 300 million people around the world every year and the number is still on the rise
We show synergistic signaling by the released curcumin during the healing process: (i) mobilization of wound site fibroblasts by activating the Wnt signaling pathway, partly mediated through Dickkopf-related protein-1, and (ii) persistent inhibition of the inflammatory response through decreased expression of monocyte chemoattractant protein-1 by fibroblasts
On the contrary, is an amorphous polymer having no crystalline structure marked by the absence of any diffraction peak in the range tested for electrospun gelatin nanofibrous mats (NMs) (Figures 1c(b))

Summary

Introduction

As a result of trauma or surgery, are estimated to affect 300 million people around the world every year and the number is still on the rise This makes wound management a significant and continuous challenge to our healthcare systems.[1] Noninvasive wound therapy, especially the utilization of plants and their products, has a long history and is still being widely practiced in many cultures.[2] One example from Asia is the use of turmeric. This plant has been used empirically for nearly 4000 years to cleanse wounds and stimulate their recovery.[3] The constant search for novel compounds in western medicine has drawn the attention of the scientific community to this ancient remedy.

Methods

Results

Conclusion