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FLUORINATED METHACRYLAMIDE CHITOSAN FOR OXYGEN DELIVERY IN WOUND HEALING AND TISSUE ENGINEERING

Patil, Pritam Suhas, Patil
http://rave.ohiolink.edu/etdc/view?acc_num=akron1532775888013965

Abstract Details

2018, Doctor of Philosophy, University of Akron, Chemical Engineering.
Worldwide, approximately 30.3 million people (9.4% population) in US had diabetes in 2015. Every year, 1.3 million new diabetes cases are identified. 3-4 million of diabetic patients develop wounds, and 1 in 5 patients in severe cases of diabetic wounds require amputation. Chronic wounds, including diabetic wounds, show oxygen tensions as low as 5 mm Hg partial pressure of oxygen, (Po2), compared to healthy tissue which is maintained at 40 mm Hg. Further complicating this, reactive oxygen species (ROS) are elevated during inflammation leading to oxidative stress. Oxygen therapy has shown benefits in healing chronic wounds while managing inflammation. Current oxygenating treatments are expensive and difficult to use. The primary objective of my project was to evaluate fluorinated methacrylamide chitosan (MACF) hydrogels to deliver beneficial levels of oxygen to acute and diabetic wounds to enhance wound healing responses. All the studies in this thesis focus on testing MACF hydrogel dressings in vitro and in vivo to establish safety and efficacy of the treatment in acute and diabetic wound models. Finally, microspheres were formulated and studied from PFC modified chitosan for oxygenation in 3D cultured spheroids and organoids, presenting a future potential extension of the MACF technology. The overall hypothesis of these studies was that MACF hydrogel dressings can provide biological levels of oxygen in wound healing thereby improving wound healing responses in both acute and chronic wound models. I also hypothesized that fluorinated chitosan-based microparticles could help reduce tissue hypoxia in tissue spheroids limiting the size of the necrotic core. To test these hypotheses following specific aims were performed: (1) Characterization of fluorinated methacrylamide chitosan hydrogels (2) Safety and efficacy testing in vivo of MACF hydrogel in acute and chronic animal wound models (3) Development of fluorinated chitosan microspheres for enhancing oxygen transport for sustained spheroid growth. From these studies, first in Aim 1, I validated the antioxidant capacity of MACF while simultaneously delivering oxygen. Secondly, expanding on the lab’s earlier work, I confirmed methacrylation and fluorination in MACF material with FTIR and NMR. Then, as a next step, I successfully demonstrated ability of MACF hydrogel dressing to sustain above atmospheric levels of oxygen for up to two days in vitro. Next, in Aim 2, I evaluated MACF hydrogel dressing in the acute rat, establishing metabolomics workflow to study treatment response, and in porcine full thickness model expanding this work to the transgenic diabetic mouse model. From all these studies I found that MACF hydrogel enhances wound healing by improving collagen synthesis, neovascularization, and maturation by keratinocyte differentiation and collagen fiber alignment. During rat study, I developed a global untargeted metabolomics workflow for pathway analysis in wound healing in order to evaluate effect of treatments on wound healing pathways. Finally, I developed chitosan-PFC microspheres for modulating local oxygen microenvironments in spheroids and organoids and demonstrated a reduction in hypoxia upon increasing % loading of microspheres in spheroids.
Nic Leipzig (Committee Chair)
George Chase (Committee Member)
Michael Cheung (Committee Co-Chair)
Matthew Becker (Committee Member)
Hossein Tavana (Committee Member)
246 p.
Bioinformatics; Biomedical Engineering; Biomedical Research; Chemical Engineering; Experiments; Immunology; Molecular Biology
Wound healing, oxygen, hydrogel, spheroids, perfluorocarbon, oxygenating biomaterial

Recommended Citations

Citations

  • Patil, Patil, P. S. (2018). FLUORINATED METHACRYLAMIDE CHITOSAN FOR OXYGEN DELIVERY IN WOUND HEALING AND TISSUE ENGINEERING [Doctoral dissertation, University of Akron]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=akron1532775888013965

    APA Style (7th edition)

  • Patil, Patil, Pritam. FLUORINATED METHACRYLAMIDE CHITOSAN FOR OXYGEN DELIVERY IN WOUND HEALING AND TISSUE ENGINEERING. 2018. University of Akron, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=akron1532775888013965.

    MLA Style (8th edition)

  • Patil, Patil, Pritam. "FLUORINATED METHACRYLAMIDE CHITOSAN FOR OXYGEN DELIVERY IN WOUND HEALING AND TISSUE ENGINEERING." Doctoral dissertation, University of Akron, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=akron1532775888013965

    Chicago Manual of Style (17th edition)

akron1532775888013965
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© 2018, all rights reserved.
This open access ETD is published by University of Akron and OhioLINK.