Abstract

Impaired angiogenesis contributes to delayed wound healing in aging. Hyaluronan (HA) has a close relationship with angiogenesis and wound healing. However, HA content decreases with age. In this study, we used high molecular weight HA (HMW-HA) (1650 kDa), and investigated its effects on wound healing in old rats by local injection. We found that HMW-HA significantly increases proliferation, migration and tube formation in endothelial cells, and protects endothelial cells against apoptosis. Local injection of HMW-HA promotes wound healing by increasing angiogenesis in old rats. HMW-HA increases the phosphorylation of Src, ERK and AKT, leading to increased angiogenesis, suggesting that local injection of HMW-HA promotes wound healing in elderly patients.

Highlights

  • With aging population increasing worldwide, delayed wound healing in the elderly is a clinical challenge [1]

  • The results showed the endotoxin amount for all hyaluronan powders was less than 0.01 EU/mg

  • This data proved that LPS and/or endotoxin are below a guard level and cellular phenomenon should be driven by hyaluronan rather than impurities on the tested sample alone

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Summary

Introduction

With aging population increasing worldwide, delayed wound healing in the elderly is a clinical challenge [1]. Wound repair is a multistep process consisting of hemostasis, inflammatory cell infiltration, tissue regrowth and remodeling [2]. In elderly population, this progression of events is altered, resulting in wounds that heal more slowly compared with wounds in young adults [3]. HA is a polysaccharide belonging to the glycosaminoglycan family of macromolecules This biopolymer consists of repeated disaccharides of (β,1– 4)-D-glucuronic acid-(β,1–3)-N-acetyl-D-glucosamine [6]. It has been reported that native high molecular-weight HA (HMW-HA) is anti-angiogenic [7], whereas degradation products that are of specific size (e.g., 3–10 disaccharide units; o-HA) exhibit pro-angiogenic activity [8, 9]. The HA content decreases in aging, and plays a significant role in wound healing

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