Tissue-engineered provisional matrix as a novel approach to enhance diabetic wound healing

Authors

  • Swathi Balaji PhD,

    1. Biomedical Engineering at School of Energy, Environmental, Biological and Medical Engineering, College of Engineering and Applied Sciences, University of Cincinnati, Cincinnati, Ohio
    2. Center for Molecular Fetal Therapy, Division of Pediatric, General, Thoracic and Fetal Surgery, Cincinnati Children's Hospital, College of Medicine, University of Cincinnati, Cincinnati, Ohio
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  • Sachin S. Vaikunth MD,

    1. Center for Molecular Fetal Therapy, Division of Pediatric, General, Thoracic and Fetal Surgery, Cincinnati Children's Hospital, College of Medicine, University of Cincinnati, Cincinnati, Ohio
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  • Stephanie A. Lang BS,

    1. Center for Molecular Fetal Therapy, Division of Pediatric, General, Thoracic and Fetal Surgery, Cincinnati Children's Hospital, College of Medicine, University of Cincinnati, Cincinnati, Ohio
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  • Abdul Q. Sheikh BS,

    1. Biomedical Engineering at School of Energy, Environmental, Biological and Medical Engineering, College of Engineering and Applied Sciences, University of Cincinnati, Cincinnati, Ohio
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  • Foong Y. Lim MD,

    1. Center for Molecular Fetal Therapy, Division of Pediatric, General, Thoracic and Fetal Surgery, Cincinnati Children's Hospital, College of Medicine, University of Cincinnati, Cincinnati, Ohio
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  • Timothy M. Crombleholme MD,

    1. Center for Molecular Fetal Therapy, Division of Pediatric, General, Thoracic and Fetal Surgery, Cincinnati Children's Hospital, College of Medicine, University of Cincinnati, Cincinnati, Ohio
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  • Daria A. Narmoneva PhD

    Corresponding author
    1. Center for Molecular Fetal Therapy, Division of Pediatric, General, Thoracic and Fetal Surgery, Cincinnati Children's Hospital, College of Medicine, University of Cincinnati, Cincinnati, Ohio
    • Biomedical Engineering at School of Energy, Environmental, Biological and Medical Engineering, College of Engineering and Applied Sciences, University of Cincinnati, Cincinnati, Ohio
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Reprint requests:

Dr. D. A. Narmoneva, 848 ERC, BME at UC, 2901 Campus Drive, ML-0012, Cincinnati, OH 45221-0012, USA.

Tel: 513 556 3997;

Fax: 513 566 4612;

Email: daria.narmoneva@uc.edu

Abstract

Inherent pathologies associated with diabetic wound microenvironment including increased proteolysis, inflammatory dysregulation, and impaired neovascularization prevent timely resolution of chronic diabetic ulcers. It is hypothesized that augmentation of local wound microenvironment with a stable provisional matrix formed by proteolysis-resistant angiogenic peptide nanofibers (NFs) will create permissive environment for attenuated inflammation, enhanced neovascularization, and improved diabetic wound healing. Using murine excisional wound healing models, full-thickness dorsal skin wounds were treated with either NFs or control solutions (phosphate buffered saline; hyaluronic acid) and analyzed for morphology, inflammatory response, neovascularization, and biomechanical properties. NF treatment of diabetic wounds stimulated formation of a robust pro-angiogenic in situ tissue-engineered provisional matrix leading to a significant decrease in wound inflammatory cell infiltration and proinflammatory interleukin-6 levels, a significant increase in endothelial and endothelial progenitor cell infiltration, vascular endothelial growth factor levels, and neovascularization (day 7), as well as improved wound morphology, accelerated wound closure, and significantly stronger repair tissue (day 28). These results suggest that appropriate design of provisional matrix may compensate for some of the complex disruptions in diabetic wound microenvironment and provide missing cues to cells and direct in situ responses toward improved healing, which is promising for future development of new therapies for diabetic ulcers.

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