The integration of several cellular responses initiates the process of wound healing. Matrix Metalloproteinases (MMPs) play an integral role in wound healing. Their main function is degradation, by removal of damaged extracellular matrix (ECM) during the inflammatory phase, breakdown of the capillary basement membrane for angiogenesis and cell migration during the proliferation phase, and contraction and remodelling of tissue in the remodelling phase. For effective healing to occur, all wounds require a certain amount of these enzymes, which on the contrary could be very damaging at high concentrations causing excessive degradation and impaired wound healing. The imbalance in MMPs may increase the chronicity of a wound, a familiar problem seen in diabetic patients. The association of diabetes with impaired wound healing and other vascular complications is a serious public health issue. These may eventually lead to chronic foot ulcers and amputation. Low intensity laser irradiation (LILI) or photobiomodulation (PBM) is known to stimulate several wound healing processes; however, its role in matrix proteins and diabetic wound healing has not been fully investigated. This review focuses on the role of MMPs in diabetic wound healing and their interaction in PBM.

Background: Collagen type I (Col-I) is a major component of the extracellular matrix and is important in wound healing processes. Several studies have shown that low-intensity laser irradiation (LILI) biostimulates Col-I synthesis both in vitro and in vivo. This study aimed to determine if LILI affects collagen production and related cellular responses in an in vitro diabetic wounded fibroblast model. Materials and Methods: This study was performed on isolated human skin fibroblasts. Different cell models (normal and diabetic wounded) were used. Cells were irradiated with 5 J/cm ² at a wavelength of 660 nm and incubated for 48 or 72 h. Nonirradiated cells (0 J/cm ² ) were used as controls. Cellular viability (Trypan blue exclusion test), morphology (bright-field microscopy), proliferation [VisionBlue™ quick cell proliferation assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay], and Col-I (enzyme-linked immunoabsorbent assay) were assessed. Results: Diabetic wounded cells irradiated with 5 J/cm ² at 660 nm showed a significant increase in cell migration, viability, proliferation, and collagen content. Conclusions: This study shows that LILI stimulates Col-I synthesis in diabetic wound healing in vitro at 660 nm.

Diabetes affects extracellular matrix (ECM) metabolism, contributing to delayed wound healing and lower limb amputation. Application of light (photobiomodulation, PBM) has been shown to improve wound healing. This study aimed to evaluate the influence of PBM on cell adhesion molecules (CAMs) in diabetic wound healing. Isolated human skin fibroblasts were grouped into a diabetic wounded model. A diode laser at 660 nm with a fluence of 5 J/cm² was used for irradiation and cells were analysed 48 h post-irradiation. Controls consisted of sham-irradiated (0 J/cm²) cells. Real-time reverse transcription (RT) quantitative polymerase chain reaction (qPCR) was used to determine the expression of CAM-related genes. Ten genes were up-regulated in diabetic wounded cells, while 25 genes were down-regulated. Genes were related to transmembrane molecules, cell–cell adhesion, and cell–matrix adhesion, and also included genes related to other CAM molecules. PBM at 660 nm modulated gene expression of various CAMs contributing to the increased healing seen in clinical practice. There is a need for new therapies to improve diabetic wound healing. The application of PBM alongside other clinical therapies may be very beneficial in treatment.