Protease sink vs. direct inhibition: mechanistic insights and clinical evidence for MMP-targeted dressings in hard-to-heal wounds

Authors

  • Navneet O. Soni Department of Pharmacology, TMC, Navi, Mumbai, Maharashtra, India

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20253383

Keywords:

Collagen dressings, Diabetic foot ulcer, Matrix metalloproteinases, Protease inhibition, Translational wound care, TLC-NOSF, Venous leg ulcer, Wound healing

Abstract

Chronic wounds are characterised by excessive matrix metalloproteinase (MMP) activity and impaired remodelling of the extracellular matrix (ECM). Dressing marketed as MMP inhibitors aims to restore protease balance, but their mechanism and clinical efficacy differ.

This review bridges the mechanistic and clinical perspectives by comparing collagen and oxidized recombinant cellulose (ORC) matrixes (protease inhibitors) with TLC-NOSF (technology lipids with nano-oligosaccharide factor). Collagen-based creams act passively as a protease sink, as a binding medium for MMPs and as an inflammatory mediator, but their clinical effectiveness is inconsistent, with most randomised studies not showing any significant improvement in complete healing. In contrast, TLC-NOSF directly inhibits MMP-2 and MMP-9, stabilises growth factors and consistently improves wound sealing and area reduction in high-quality blinded clinical trials. Mechanism of action predicts clinical outcome: passive binding to protease (collagen) provides modest, variable benefits, while active, specific inhibition (TLC-NOSF) is correlated with reproducible efficacy and support from guidelines. Mechanistic-clinical integration underlines the importance of selection of dressings based on biological plausibility as well as experimental evidence.

 

Metrics

Metrics Loading ...

References

Veves A, Sheehan P, Pham HT. A randomized, controlled trial of Promogran (a collagen/oxidized regenerated cellulose dressing) vs standard treatment in the management of diabetic foot ulcers. Arch Surg. 2002;137(7):822–7. DOI: https://doi.org/10.1001/archsurg.137.7.822

Donaghue VM, Chrzan JS, Rosenblum BI, Giurini JM, Habershaw GM, Veves A. Evaluation of a collagen–alginate wound dressing in the management of diabetic foot ulcers. Adv Wound Care. 1998;11(3):114–9.

Gottrup F, Apelqvist J, Price P, Holstein PE, Jørgensen B, Friis GJ, et al. Randomized controlled open-label multicentre study on collagen/oxidized regenerated cellulose/silver treatment. Wound Repair Regen. 2013;21(2):216–25. DOI: https://doi.org/10.1111/wrr.12020

Cullen B, Ivins N, Gibson MC, Harding KG. Randomized controlled trial of collagen/oxidized regenerated cellulose dressing for venous leg ulcers. Int Wound J. 2017;14(5):1040–7.

Romanelli M, Dini V, Bertone M, Barbanera S, Brandi C. Randomized controlled trial of collagen/oxidized regenerated cellulose dressing in the treatment of venous leg ulcers. Wounds. 2015;27(6):141–6.

Nisi G, Brandi C, Grimaldi L, Calabrò M, D’Aniello C. Use of a collagen–oxidized regenerated cellulose dressing in pressure ulcer treatment: a randomized study. J Wound Care. 2005;14(6):290–s2.

Kloeters O, Unglaub F, de Laat E, van Zuijlen PP, Ulrich D. Prospective randomized controlled pilot trial of collagen dressing in pressure ulcers. Adv Skin Wound Care. 2016;29(7):318–23.

Vin F, Teot L, Meaume S. The healing properties of Promogran in venous leg ulcers. J Wound Care. 2002;11(9):335–41. DOI: https://doi.org/10.12968/jowc.2002.11.9.26438

Margolis DJ, Kantor J, Santanna J, Strom BL, Berlin JA. Effectiveness of a collagen-based dressing for the treatment of chronic pressure ulcers. Wound Repair Regen. 2003;11(5):327–32.

Lobmann R, Schultz G, Lehnert H. Protease-modulating matrix dressing in the treatment of diabetic foot ulcers: results of a randomized controlled trial. ExpClinEndocrinol Diabetes. 2002;110(8):440–5.

Motta G, De Caridi G, Massara M, Spinelli F, Stilo F, Serra R. Collagen-based dressing in the management of chronic venous leg ulcers: a randomized controlled trial. Int Wound J. 2015;12(2):153–8.

Kravitz SR, McGuire J, Zinszer KM. Randomized controlled trial on the efficacy of Promogran versus control dressing in diabetic foot ulcers. Diabetes Care. 2003;26(11):3026–31.

Vincent JR, Dalal M, Brandt K, Randall K. Randomized trial of collagen/ORC dressing versus standard care in diabetic foot ulcer patients. J Am Podiatr Med Assoc. 2009;99(4):301–5.

Schmutz JL, Meaume S, Fays S, Ourabah Z, Guillot B, Vin F, et al. Evaluation of TLC-NOSF dressing versus Promogran in venous leg ulcers: a multicentre randomized controlled trial. Int Wound J. 2008;5(2):172–82. DOI: https://doi.org/10.1111/j.1742-481X.2008.00453.x

Meaume S, Truchetet F, Cambazard F, Lok C, Debure C, Dalac S, et al. A randomized, double-blind trial of a TLC-NOSF wound dressing in venous leg ulcers. Wound Repair Regen. 2012;20(4):500–11. DOI: https://doi.org/10.1111/j.1524-475X.2012.00797.x

Edmonds M, Lázaro-Martínez JL, Alfayate-García JM, Martini J, Petit JM, Rayman G, et al. Sucrose octasulfate dressing versus control dressing in neuroischaemic diabetic foot ulcers (Explorer study): a randomized, double-blind clinical trial. Lancet Diabetes Endocrinol. 2018;6(3):186–96. DOI: https://doi.org/10.1016/S2213-8587(17)30438-2

Dissemond J, Augustin M, Dietlein M, Faust U, Keuthage W, Lobmann R, Münter K-C, Strohal R, Stücker M, Traber J, Vanscheidt W, Läuchli S. Efficacy of MMP-inhibiting wound dressings in the treatment of hard-to-heal wounds: a systematic review. J Wound Care. 2020;29(2):103-18. DOI: https://doi.org/10.12968/jowc.2020.29.2.102

Downloads

Published

2025-10-24

How to Cite

Soni, N. O. (2025). Protease sink vs. direct inhibition: mechanistic insights and clinical evidence for MMP-targeted dressings in hard-to-heal wounds. International Journal of Basic & Clinical Pharmacology, 14(6), 1054–1059. https://doi.org/10.18203/2319-2003.ijbcp20253383