Far-Infrared Therapy Accelerates Diabetic Wound Healing via Recruitment of Tissue Angiogenesis in a Full-Thickness Wound Healing Model in Rats

Rong-Fu Chen,Yur-Ren Kuo,Su-Shin Lee,Yun-Nan Lin,Chun-Ting Wang,Shu-Hung Huang,Keng-Fan Liu,Yi-Chia Wu

doi:10.3390/biomedicines9121922

Abstract

Far-infrared ray (FIR) therapy has been applied in the tissue regeneration field. Studies have revealed that FIR could enhance wound healing. However, the biological effects of FIR on diabetic wounds remain unclear. Our study aims to investigate whether FIR could accelerate diabetic wound healing and analyze the biomechanisms. A dorsal skin defect (area, 6 × 5 cm2) in a streptozotocin (STZ)-induced diabetes rodent model was designed. Thirty-two male Wistar rats were divided into 4 groups (n = 8 each subgroup). Group 1 consisted of sham, non-diabetic control; group 2, diabetic control without treatment; group 3, diabetic rats received 20 min FIR (FIR-20, 20 min per session, triplicate/weekly for 4 weeks) and group 4, diabetic rats received 40 min FIR (FIR-40, 40 min per session, triplicate in one week for 4 weeks). The wound healing was assessed clinically. Skin blood flow was measured by laser Doppler. The vascular endothelial growth factor (VEGF), 8-hydroxy-2-deoxyguanosine (8-OHdG), eNOS, and Ki-67, were analyzed with immunohistochemical (IHC) staining. Laser Doppler flowmetry analysis of the blood flow of wounding area revealed the blood flow was higher in diabetic rats who received 40 min FIR (FIR-40) as compared to that in FIR-20 group. The wounding area was significantly reduced in the FIR-40 group than in the diabetic control groups. Histological findings of peri-wounding tissue revealed a significant increase in the neo-vessels in the FIR-treated groups as compared to the controls. IHC staining of periwounding biopsy tissue showed significant increases in angiogenesis expressions (VEGF, eNOS, and EGF), cell proliferation (Ki-67), and suppressed inflammatory response and oxygen radicles (CD45, 8-OHdG) expressions in the FIR-treated groups as compared to that in controls. Treatment with the optimal dosage of FIR significantly facilitated diabetic wound healing and associated with suppressed pro-inflammatory response and increased neovascularization and tissue regeneration.

Highlights

Chronic wounds occur commonly and reduce the quality of life of those affected, posing a relevant clinical and socioeconomic burden
A previous study showed that far-infrared radiation (FIR), independent of its thermal effects, enhances blood perfusion indicating that FIR irradiation could regulate angiogenesis
The blood perfusion in the wound area revealed no significant difference between FIR-20 and FIR-40 groups on day 4 after

Summary

Introduction

Chronic wounds occur commonly and reduce the quality of life of those affected, posing a relevant clinical and socioeconomic burden. Skin wound healing is a complex multistep process involving the coordination of activities of multiple tissue and cell types [1]. Diabetic foot ulcers are a significant intricacy of diabetes mellitus and are probably the Biomedicines 2021, 9, 1922. Biomedicines 2021, 9, 1922 major component of the diabetic foot [2,3]. Multiple main signaling transduction is enacted during the process of wound healing; these pathways incorporate the mitogen-activated protein kinase-related pathway, Wnt/β-catenin, and vascular endothelial growth factor (VEGF) pathways [1,4,5]. PBM can bring beneficial therapeutic effects, including relief of pain or inflammation, immunomodulation, and promotion of tissue regeneration and wound healing [1,8]. Much attention has been paid to that far-infrared radiation (FIR)

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