MMPs in Wound Healing

MMPs play a critical role in the process of wound healing, excessive MMP activity can lead to chronic wounds that fail to heal. Chronic wounds are wounds that fail to heal within 3 months and are often associated with underlying medical conditions such as diabetes, vascular disease, and immunosuppression. In chronic wounds, MMPs are produced by inflammatory cells, fibroblasts, and keratinocytes in the wound bed. These enzymes break down extracellular matrix proteins, such as collagen and fibronectin, that are necessary for the formation of new tissue and blood vessels. Chronic wounds are often characterized by an imbalance between MMPs activity and the activity of tissue inhibitors of metalloproteinases (TIMPs), which are natural inhibitors of MMPs . 

Several types of MMPs have been implicated in chronic wound healing: MMP-1, MMP-2, MMP-3, MMP-8, and MMP-9. These MMPs have been shown to be elevated in chronic wounds compared to acute wounds, indicating their potential role in delaying wound healing.

MMP inhibitors have been studied as a potential treatment for chronic wounds to block the activity of these enzymes and promote wound healing.

There are several types of MMP inhibitors that have been studied as potential treatments for chronic wounds:

1. Synthetic MMP inhibitors: These are small molecule drugs that are designed to specifically inhibit MMP activity. Examples of synthetic MMP inhibitors include batimastat, marimastat, and prinomastat.
2. Natural MMP inhibitors: These are compounds found in natural products that have been shown to inhibit MMP activity. Examples of natural MMP inhibitors include green tea polyphenols, curcumin, and resveratrol.
3. Antibodies: These are protein molecules that can be designed to specifically bind and inhibit MMP activity. Examples of MMP-inhibiting antibodies include DX-2400 and GS-5745.
4. Endogenous inhibitors: These are natural proteins that are produced by the body to inhibit MMP activity. Examples of endogenous MMP inhibitors include tissue inhibitors of metalloproteinases (TIMPs), alpha-2-macroglobulin, and RECK (reversion-inducing cysteine-rich protein with kazal motifs).

REFERENCES
Gutierrez-Fernandez A., Inada M., Balbin M., Fueyo A., Pitiot A.S., Astudillo A., Hirose K., Hirata M., Shapiro S.D., Noel A., et al. Increased inflammation delays wound healing in mice deficient in collagenase-2 (MMP-8) FASEB J. 2007;21:2580–2591.
Rohani M.G., Parks W.C. Matrix remodeling by MMPs during wound repair. Matrix Biol. 2015;44–46:113–121.
Muller M., Trocme C., Morel F., Halimi S., Benhamou P.Y. Increased matrix metalloproteinase-9 predicts poor wound healing in diabetic foot ulcers: Response to Liu et al. Diabetes Care. 2009;32:e138.