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Published on: March 3, 2023
Swift Downregulation of Gelatinases (MMP-2, MMP-9) in Neuropathic Diabetic Foot Ulcers Treated With Total Contact
Oscar M Alvarez1, Lee Markowitz2, Neh Onumah2
1Center for Curative and Palliative Wound Care, Calvary Hospital, Bronx NY; Vascular and Wound Care Center, University Hospital, Newark, NJ.
Objective:
The aim of this study is to evaluate how treatment with total contact cast (TCC) affects the balance of proteases in diabetic foot ulcers (DFUs) as they heal.
Materials And Methods:
This was a prospective observational study of 22 eligible patients with neuropathic plantar DFUs in a hospital-based wound care center. All patients treated with TCC had adequate arterial circulation (ankle-brachial index > 0.75), no sign of infection, and all DFUs were grade 1A according to the University of Texas Diabetic Wound Classification System. Patients had weekly follow-up visits for wound evaluation and reapplication of the TCC. Wound tissues were obtained at baseline (week 0 prior to initial treatment), week 3, week 6, and week 12. Tissue homogenates were analyzed for matrix metalloprotease (MMP) 2, MMP-9, tissue inhibitor matrix metalloproteinase (TIMP) 1, and TIMP-2. Wound measurements were obtained at weekly follow-up visits, and healing rates were calculated by photodigital planimetry.
Results:
Treatment with TCC for 3 weeks resulted in a 20% decrease in MMP-2 (P = .031) and 44% decrease in MMP-9 (P = .018). By week 6, MMP-2 and MMP-9 levels were reduced by 37% and 55%, respectively. Tissue inhibitor matrix metalloproteinase 1 increased by 42% (P = .033) and TIMP-2 by 44% (P = .04) after 6 weeks of therapy with TCC.
Conclusions:
This significant and rapid drop of both MMP-2 and MMP-9 strongly suggests a decline of the inflammatory phase and initiation of the proliferation phase.
Insights
Total contact cast (TCC) therapy rapidly reduces matrix metalloproteinases (MMPs) in diabetic foot ulcers (DFUs), indicating a shift from inflammation to healing. This protease balance change supports TCC
Area of Science:
- Wound healing research
- Diabetic complications
- Biochemistry of tissue repair
Background:
- Diabetic foot ulcers (DFUs) present a significant clinical challenge.
- Protease imbalance, particularly elevated matrix metalloproteinases (MMPs), is implicated in non-healing DFUs.
- Total contact cast (TCC) is a standard treatment for DFUs, but its biochemical effects on protease activity are not fully understood.
Purpose of the Study:
- To investigate the impact of TCC treatment on protease and protease inhibitor levels in neuropathic plantar DFUs.
- To correlate changes in MMPs and tissue inhibitors of metalloproteinases (TIMPs) with wound healing progression.
- To assess the temporal dynamics of protease activity during TCC therapy.
Main Methods:
- Prospective observational study of 22 patients with neuropathic plantar DFUs treated with TCC.
- Weekly wound evaluations and TCC reapplication.
- Wound tissue sampling at baseline, 3, 6, and 12 weeks for analysis of MMP-2, MMP-9, TIMP-1, and TIMP-2.
- Wound healing rates calculated by photodigital planimetry.
Main Results:
- TCC treatment led to a significant decrease in MMP-2 (20% at 3 weeks, 37% at 6 weeks) and MMP-9 (44% at 3 weeks, 55% at 6 weeks).
- Levels of tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) increased by 42% and TIMP-2 by 44% after 6 weeks of TCC therapy.
- These biochemical changes correlated with observed wound healing rates.
Conclusions:
- The rapid reduction in MMPs and increase in TIMPs suggest that TCC therapy effectively modulates the protease balance in DFUs.
- This modulation indicates a transition from the inflammatory phase to the proliferative phase of wound healing.
- TCC therapy promotes a favorable biochemical environment for DFU healing.
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