Based on Clinical Research Matrix Metalloprotease (MMP) Inhibitors to Promote Diabetic Wound Healing

Abstract

Chronic inflammation is a common factor in obesity, diabetes mellitus, and the complications of diabetes, including diabetic wounds. These ulcers are characterized by persistent lesions that are challenging to heal, significantly decreasing patients’ quality of life and imposing a substantial financial burden on society. MMP are zinc endopeptidases that play a role in wound healing in response to various stimuli, including diabetes mellitus. MMP levels fluctuate throughout the wound healing process in diabetic patients' serum, skin tissues, and wound fluid, indicating their potential as biomarkers for diabetic foot ulcers. Targeting MMP has emerged as a promising strategy for treating diabetic wounds, as these enzymes are involved in critical biological processes related to wound healing, including extracellular matrix secretion, angiogenesis, granulation tissue formation, collagen growth, re-epithelization, inflammatory response, and oxidative stress.

Nanozymes for the Therapeutic Treatment of Diabetic Foot Ulcers

“…However, when the body requires tissue remodeling (e.g., wound healing), the expression of MMPs is upregulated in a variety of cells within the wound (keratinocytes, fibroblasts, endothelial cells, and inflammatory cells), and is also induced in response to signals such as ROS, proinflammatory cytokines, and ECM . Tissue inhibitors of MMPs (TIMPs) can inhibit the overexpression of MMPs, and the two play an important synergetic role in wound healing . DFU exhibits significantly elevated levels of MMPs (mainly collagenase (MMP-1 and MMP-8), gelatinase (MMP-2 and MMP-9), and matrix lysin (MMP-10)) and low-level expression of TIMPs. − At this point, the balance between the activity of MMPs and the inhibitory effect of TIMPs is disrupted, and growth factors and ECM are excessively degraded, ultimately leading to delayed or arrested wound closure.…”

“…59 Tissue inhibitors of MMPs (TIMPs) can inhibit the overexpression of MMPs, and the two play an important synergetic role in wound healing. 60 DFU exhibits significantly elevated levels of MMPs (mainly collagenase (MMP-1 and MMP-8), gelatinase (MMP-2 and MMP-9), and matrix lysin (MMP-10)) and low-level expression of TIMPs. 61−64 At this point, the balance between the activity of MMPs and the inhibitory effect of TIMPs is disrupted, and growth factors and ECM are excessively degraded, ultimately leading to delayed or arrested wound closure.…”