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Investigation Physicochemical, Mechanical and Biological Properties of Chitosan-Graphene Oxide Electrospun Nanocomposite with Drug Release Capability as a Temporary Skin Graft

Mahmoudi, Nafiseh | 2016

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 49109 (07)
  4. University: Sharif University of Technology
  5. Department: Materials Science and Engineering
  6. Advisor(s): Simchi, Abdolreza
  7. Abstract:
  8. In recent years, temporary skin grafts based on natural biopolymers modified with carbon nanostructures has received considerable for wound healing applications. In this study, Nanofibrous structures that mimic the native extracellular matrix and promote cell adhesion have attracted considerable interest for biomedical applications. Chitosan-polyvinylpyrrolidone (CS/PVP) films containing graphene oxide (GO) nanosheets (~1 nm thickness and micrometer length) were prepared by solvent casting methods. Experimental results showed that PVP concentration had a critical role on the water vapor permeability, transparency, hydrophilicity and thermal stability of the nanocomposite films. Antibacterial assay showed an improved bactericidal capacity of the composite films against gram-positive Staphylococcus aureus and gram-negative Escherichia coli bacteria. Then, GO-modified Nano-fibrous chitosan-based biopolymers skin graft crosslinked by genipin with physico-mechanical properties close to natural skin were prepared by electrospinning of highly concentrated chitosan(80 vol%)- polyvinylpyrrolidone(20 vol%) solutions containing graphene oxide (GO) nanosheets(0-2 wt%). It is shown that GO nanosheets significantly change the conductivity and viscosity of highly-concentrated chitosan solutions, so that ultrafine and uniform fibers with an average diameter of 60 nm are spinnable. The GO-reinforced nanofibers with controlled pore structure exhibit enhanced elastic modulus and tensile strength (150-300%) with a controllable water permeability to meet the required properties of natural skins. Major challenges still remain considering physico-mechanical properties, which should be close to natural skin, as well as in-deep pre-clinical testing of the developed materials to ensure biological performance and toxicity effect in-vivo. we show superior acute-wound healing effect of graphene oxide nanosheets embedded in ultrafine biopolymer fibers (60 nm) on adult male rats. No surfactants and organic solvents were utilized to ensure high biocompatibility of the fibrous structure. In-vitro evaluations by human skin fibroblast cells including live and dead and MTT results show that GO promote cell viability of porous nanofibrous membrane while providing enhanced bactericidal capacity. In-vivo studies on rat’s skin determine accelerated healing effect, i.e. a large open wound (5/1×5/1 cm2) is fully regenerated with 14-day of post operation compared to partial healing of shrill gauze sponge (as the control). Pathological studies supports thick dermis formation and complete Epithelialization in the presence of 5/1wt%GO nanosheets. Over 99% wound healing occurred after 21 days in specimen with skin graft containing 5/1wt% GO while this would takes weeks for the control. Therefore, the developed materials have a high potential to be used as temporary skin grafts as pre-clinical testing has shown
  9. Keywords:
  10. Chitosan ; Polyvinylpyrolidon ; Graphene Oxide ; Biocompatibility ; Electrospinning ; Wound Dressing

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