Nanofiber-based therapy for diabetic wound healing: a mechanistic study

Chronic diabetic wounds are a serious complication of diabetes mellitus, representing more than 27% of total annual diabetic health care costs which exceed $116 billion annually in the US alone. Diminished infiltration of new blood vessels (neovascularization) into the wound is a major factor contributing to the impaired healing of diabetic ulcers. A previous study has shown that the wounds treated with RAD16-II peptide nanofibers resulted in increased infiltration of both endothelial cells (ECs) and endothelial progenitor cells (EPCs) into the wounds in diabetic mouse model, resulting in enhanced neovascularization and accelerated wound healing. However, in order to utilize the full potential of the peptide nanofibers for treatment of diabetic ulcers, it is necessary to understand the mechanisms by which it works. The long-term goal of this research is to develop a therapy to create a wound microenvironment which enhances neovascularization and overall healing in diabetic wounds by utilizing peptide nanofibers. The studies in this dissertation contribute to this goal by investigating the nature of interactions between ECs and nanofibers, as well as the role of bone marrow-derived EPCs during nanofiber-mediated neovascularization. The central hypothesis of this research is that the RAD16-II peptide nanofibers enhance wound neovascularization and improve diabetic wound healing by regulating both angiogenesis (by ECs) and vasculogenesis (by EPCs). The results from this dissertation research help identify the roles of ECs and EPCs during nanofiber-mediated neovascularization. The results from this study demonstrate that the nanofibers promote wound neovascularization mostly by increasing EC recruitment via an integrin dependent mechanism, with a limited contribution from bone marrow-derived EPCs. The findings of this study will contribute towards developing an optimal microenvironment to enhance diabetic wound neovascularization and for vascular tissue engineering applications.

Name thesis:degree_name

PhD

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Engineering and Applied Science: Biomedical Engineering

Grantor dc:publisher

University of Cincinnati

Year dc:date

2012

Author dc:creator

• Cho, Hongkwan

Contributors dc:contributor

• Narmoneva, Daria

• Biomedical Research
• Angiogenesis
• vasculogenesis
• diabetic wound
• self-assembling peptide nanofibers
• endothelial progenitor cells

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=ucin1352402217

OAI identifier oai:identifier

oai:etd.ohiolink.edu:ucin1352402217