Influence of Reactive Oxygen Species on Wound Healing and Tissue Regeneration in Periodontal and Peri-Implant Tissues in Diabetic Patients

Abstract

Diabetes mellitus (DM) is associated with periodontal disease. Clinically, periodontal treatment is less effective for patients with DM. Oxidative stress is one of the mechanisms that link DM to periodontitis. The production of reactive oxygen species (ROS) is increased in the periodontal tissues of patients with DM and is involved in the development of insulin resistance in periodontal tissues. Insulin resistance decreases Akt activation and inhibits cell proliferation and angiogenesis. This results in the deterioration of wound healing and tissue repair in periodontal tissues. Antioxidants and insulin resistance ameliorants may inhibit ROS production and improve wound healing, which is worsened by DM. This manuscript provides a comprehensive review of the most recent basic and clinical evidence regarding the generation of ROS in periodontal tissues resulting from microbial challenge and DM. This study also delves into the impact of oxidative stress on wound healing in the context of periodontal and dental implant therapies. Furthermore, it discusses the potential benefits of administering antioxidants and anti-insulin resistance medications, which have been shown to counteract ROS production and inflammation. This approach may potentially enhance wound healing, especially in cases exacerbated by hyperglycemic conditions.

Keywords: diabetes; oxidative stress; periodontitis; reactive oxygen species; wound healing.

Figure 1

Upregulated reactive oxygen species (ROS) in the periodontal tissues of patients with DM. In a microbial invasion, fragments of periodontal pathogens such as P. gingivalis and lipopolysaccharides (LPS) invade gingival tissues, activating the inflammatory response. Polymorphonuclear neutrophils (PMNs) gather in the gingiva sulcus and periodontal tissues, release inflammatory mediators, and cause the overproduction of ROS, resulting in oxidative stress within the tissues. ROS can trigger cytotoxic effects on periodontal-resident cells through fibroblast migration and proliferation, induce osteoblast apoptosis, and activate osteoclasts. Furthermore, ROS can damage proteoglycan, hyaluronan, and collagen, leading to connective tissue breakdown and impairing wound healing in periodontal disease. Similarly, in DM conditions, hyperglycemia-induced oxidative stress in periodontal tissue results in delayed gingival wound healing in patients with periodontitis and DM.