Page 5 - manuscript_ijb05596

1. Introduction

Diabetes mellitus (DM), as a typical metabolic disorder, was characterized by

persistently abnormally elevated blood glucose levels. Its pathological basis was closely
related to insufficient insulin secretion or functional defects, which caused multiple organ

damage and a series of serious complications, such as renal impairment, visual impairment,

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neuropathy, and cardiovascular disease. Epidemiological data and the Diabetes Atlas
from the International Diabetes Federation (IDF) showed that the global prevalence of

diabetes had increased dramatically by 2021, and the number of patients reached 536

million, which was expected to increase to 783 million by 2025. 3-5 It was noteworthy

that China held the top position globally in terms of the diabetic patient population,

with the number of adult diabetics reaching a staggering 148 million in 2022,

representing approximately 18% of the worldwide total. This situation significantly

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impacted patients' lives and imposed a considerable strain on the healthcare system.
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During normal wound healing, superoxide anion (O ) and hydrogen peroxide (H2O2)
are essential to prevent infection. And small amounts of reactive oxygen species (ROS)

could promote collagen and fibronectin production, neovascularization, fibroblast
proliferation and migration, and epithelial tissue regeneration. However, in diabetic

patients, hyperglycemia not only provided a favorable environment for bacterial

proliferation but also led to a significant increase in reactive oxygen species (ROS) levels

in the body by activating polyol pathways and accumulating advanced glycation end

products (AGEs), thereby causing major changes in skin structure and function,

damaging the mechanical integrity of the skin, and weakening its self-repair ability.

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Eventually, chronic wounds form. From the molecular mechanism perspective,
hyperglycemia actively exerted negative impacts on cell function, vascular endothelial

growth factor (VEGF) expression and inflammatory response. For example, it inhibited

the proliferation and migration of fibroblasts, down-regulated the expression of VEGF,

induced neovascularization dysfunction, led to insufficient blood supply of local tissues

and excessive expression of pro-inflammatory factors, and further aggravated the

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complexity of wound healing.

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