ArticleProceedings of the National Academy of Sciences of the United States of America2015
Acceleration of diabetic wound healing using a novel protease-anti-protease combination therapy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.
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Who cites it
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 173 citations in OpenAlex.
- Natural Bioactive-Based Advanced Wound Dressings for Diabetic Wound Healing: A Systematic Review of Emerging Biomaterial Platforms.International journal of nanomedicine · 2026Pooled it
- Systematic engineering of Layer-by-Layer anti-miR coated wound dressings with tunable release kinetics.Biomaterials advances · 2026Article
- In Situ Genetic Engineering Facilitates MMP-9-Responsive TIMP1 Release Through Proteolytic Cleavage to Boost Diabetic Wound Healing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Research progress of responsive electrospun dressings for precise monitoring and treatment of diabetic wounds.Burns & trauma · 2026Review
- Immunomodulatory Mechanisms of Chronic Wound Healing: Translational and Clinical Relevance.MedComm · 2025Review
- Comparison of Serum Matrix Metalloproteinase-9 Levels in Diabetic and Non-diabetic Chronic Wounds.Cureus · 2025Article
- Cell migration in diabetic wound healing: Molecular mechanisms and therapeutic strategies (Review).International journal of molecular medicine · 2025Review
- Targeting Cathepsin K to Accelerate Diabetic Wound Healing.ACS pharmacology & translational science · 2025Article
- Role of MMP-2, MMP-9, TIMP-1, and TIMP-2 in children with ventricular septal defect.Biomolecules & biomedicine · 2025Article
- CDK1-loaded extracellular vesicles promote cell cycle to reverse impaired wound healing in diabetic obese mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Mitochondrial dysfunction in diabetic ulcers: pathophysiological mechanisms and targeted therapeutic strategies.Frontiers in cell and developmental biology · 2025Review
- Inflammation, diabetic foot and related treatments.Frontiers in endocrinology · 2025Review
- Application and development of stimulus-responsive hydrogel biomaterials for diabetic wound healing: a literature review.Frontiers in medicine · 2025Review
- Matrix Metalloproteinases on Skin Photoaging.Journal of cosmetic dermatology · 2024Review
- Article
- Targeting Matrix Metalloproteinase-9 for Therapeutic Intervention in Diabetic Foot Ulcers.ACS pharmacology & translational science · 2024Review
- Expression of matrix metalloproteinase-9 (MMP-9) in human skin within 1 hour after injury through immunohistochemical staining: a pilot study.International journal of legal medicine · 2024Article
- Article
- Tissue Regeneration and Remodeling in Rat Models after Application ofGels (Basel, Switzerland) · 2024Article
- Signaling Pathways Triggering Therapeutic Hydrogels in Promoting Chronic Wound Healing.Macromolecular bioscience · 2024Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Nonhealing chronic wounds are major complications of diabetes resulting in >70,000 annual lower-limb amputations in the United States alone. The reasons the diabetic wound is recalcitrant to healing are not fully understood, and there are limited therapeutic agents that could accelerate or facilitate its repair. We previously identified two active forms of matrix metalloproteinases (MMPs), MMP-8 and MMP-9, in the wounds of db/db mice. We argued that the former might play a role in the body's response to wound healing and that the latter is the pathological consequence of the disease with detrimental effects. Here we demonstrate that the use of compound ND-336, a novel highly selective inhibitor of gelatinases (MMP-2 and MMP-9) and MMP-14, accelerates diabetic wound healing by lowering inflammation and by enhancing angiogenesis and re-epithelialization of the wound, thereby reversing the pathological condition. The detrimental role of MMP-9 in the pathology of diabetic wounds was confirmed further by the study of diabetic MMP-9-knockout mice, which exhibited wounds more prone to healing. Furthermore, topical administration of active recombinant MMP-8 also accelerated diabetic wound healing as a consequence of complete re-epithelialization, diminished inflammation, and enhanced angiogenesis. The combined topical application of ND-336 (a small molecule) and the active recombinant MMP-8 (an enzyme) enhanced healing even more, in a strategy that holds considerable promise in healing of diabetic wounds.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.