Dose–Response Relationship of Photobiomodulation Therapy on Matrix Metalloproteinase in Healing Dynamics of Diabetic Neuropathic Ulcers—An in vivo Study

Abstract

Individuals with diabetic foot ulcers have overlapped the inflammatory, proliferative and remodeling phase, making the tissue vulnerable to delayed healing responses. We aimed to establish the dose–response relationship of photobiomodulation therapy of different doses and matrix metalloproteinases in the healing dynamics of diabetic neuropathic ulcers. Diabetes was induced in 126 Albino Wistar rats, and neuropathy was induced to the hind paw by a sciatic nerve injury method. An excisional wound was created on the neuropathy‐induced leg. Photobiomodulation therapy of dosages 4, 6, 8, 10, 12 and 15 J cm−2 and wavelength 655 nm and 808 nm was irradiated. Photobiomodulation therapy of dosages 4, 6 and 8 J cm−2 showed better wound healing properties with optimized levels of matrix metalloproteinases‐1 and 8. We observed a strong dose response in the experimental group treated with 6 and 8 J cm−2. The findings from the present study conclude that photobiomodulation therapy of dosages 4, 6 and 8 J cm−2 is suggestive of usefulness in diabetic neuropathic ulcer healing. Markers like matrix metalloproteinases may give a clear direction on response to the therapy. Based on the findings from the present study, we recommend to validate the findings for safety and efficacy in future through human prospective randomized controlled clinical trials.

Advanced multifunctional hydrogels for diabetic foot ulcer healing: Active substances and biological functions

“…Peripheral sensory neuropathy, the primary cause of DFU, can make patients unaware of trauma 19,20 . Among them, motor neuropathy can cause the anterior tibial muscle atrophy and foot deformity, resulting in abnormally high plantar pressure, following by the occurrence and development of foot ulcers 21–23 .…”

“…Peripheral sensory neuropathy, the primary cause of DFU, can make patients unaware of trauma. 19 , 20 Among them, motor neuropathy can cause the anterior tibial muscle atrophy and foot deformity, resulting in abnormally high plantar pressure, following by the occurrence and development of foot ulcers. 21 , 22 , 23 Besides, autonomic neuropathy often leads to anhidrosis of lower limbs and makes the foot skin dry and chapped, thus providing a channel for bacterial invasion.…”