Engineering medical device surfaces with zwitterionic polymer and chitosan/dexamethasone to improve anti-adhesion and anti-bacterial/anti-inflammatory properties

Author(s)
권호준
Alternative Author(s)
Kwon, Ho Joon
Advisor
박기동
Department
일반대학원 분자과학기술학과
Publisher
The Graduate School, Ajou University
Publication Year
2022-02
Language
eng
Keyword
anti-fouling propertiesanti-inflammation properties.antibacterial propertieschitosandexamethasonepolydopaminesurface modificationtyrosinase-catalyzed reactionzwitterion
Alternative Abstract
With the gradual development of medical technology, various biomaterials capable of supporting or replacing the damaged tissue have been developed and utilized. However, implantation of biomaterials into the body cannot always be free from side effects such as thrombosis, infection, and foreign body reaction, which may cause discomfort and even threaten the patient’s life. Since all of these side effects occur due to the interaction between the surface of the implantation material and the host's internal environment, the need for surface modification technology to ensure safer implantation of the biomaterial is emerging. The main purpose of this dissertation is to introduce various bio-functionalities to biomaterial surface via dopamine-derived surface grafting methods that can modify the material surface regardless of the type of biomaterial. In chapter 2, poly(sulfobetaine-co-tyramine), a tyramine-conjugated sulfobetaine polymer, was synthesized and simply grafted onto the surface of polyurethane via a tyrosinase-mediated reaction. Surface characterization by water contact angle measurements, X-ray photoelectron spectroscopy and atomic force microscopy demonstrated that the zwitterionic polymer was successfully introduced onto the surface of polyurethane and remained stable for 7 days. In vitro studies revealed that poly(sulfobetaine-co-tyramine)-coated surfaces dramatically reduced the adhesion of fibrinogen, platelets, fibroblasts, and S. aureus by over 90% in comparison with bare surfaces. These results proved that polyurethane surfaces grafted with poly(sulfobetaine-co-tyramine) via a tyrosinase-catalyzed reaction could be promising candidates for an implantable medical device with excellent bioinert abilities. In chapter 3, Chitosan immobilized and dexamethasone loaded surface that can solve both inflammation and infection problems was developed. Also, when it used in proper concentrations, dexamethasone can promote osseointegration by differentiating stem cells into osteoblasts. To fabricate funtional surface, phenylboronic acid-modified chitosan was immobilized through polydopamine assisted reaction. Then, dexamethasone-loaded β-cyclodextrin was treated to generate the phenylboronic ester bond between chitosan-phenylboronic acid and cyclodextrin. Scanning electron microscope and energy dispersive X-ray spectroscopy confirmed the successful conjugation of chitosan derivative and β-cyclodextrin onto surface. The anti-inflammatory effect of surface was evaluated by macrophage polarization test. Immunofluorescent staining of CD 163 and increased amount of TGF-β which are the markers of M2 macrophage, indicating anti-inflammatory effect of dexamethasone-loaded surface. Antibacterial assay also showed the significant bactericidal effect of chitosan immobilized surface against gram negative and gram positive strain, E. coli and S. aureus. Also, assays using ARS and ALP demonstrated the osteogenic effect of modified surface. The results indicated that chitosan/dexamethasone surface modification could serve as potential antibacterial/anti-inflammatory implant surface modification methods.
URI
https://dspace.ajou.ac.kr/handle/2018.oak/20577
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Graduate School of Ajou University > Department of Molecular Science and Technology > 4. Theses(Ph.D)
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