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Multi-functionalization of Biomaterials Surfaces through Tyrosinase-mediated Reaction for Cardiovascular Therapy
- Author(s)
- TRAN DIEU LINH
- Advisor
- Ki Dong Park
- Department
- 일반대학원 분자과학기술학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2021-02
- Language
- eng
- Keyword
- anti-inflammation properties.; anti-thrombogenic properties; antibacterial properties; cardiovascular diseases; implantable cardiovascular devices; surface modification; tyrosinase-mediated reaction
- Alternative Abstract
- Nowadays, the important role of implantable cardiovascular devices in the treatment of cardiovascular disease is undeniable. The functions of the implantable cardiovascular devices are not only about replacing or supporting the damaged part of the heart, but they also improve the heart functions. However, the implantation of the foreign biomaterials into human body always lead to series of damage and provoke a series of host responses at the implant-tissue interface such as infection, thrombus formation, and inflammation. These responses can cause the failure of implants, increased medical costs, and even life-threatening effect. Regulating the implant-associated tissue responses is one of the biggest challenges for the clinical application of the implantable devices. Therefore, the development of simple, safe and highly effective surface modifications to eliminate these responses is required. The objectives of this dissertation are to develop the multifunctional surfaces with enhanced anti-infection, anti-thrombosis, and anti-inflammation to improve the clinical performance of blood contacting devices, especially in treatment of CDVs, through tyrosinase-catalysed reaction. In chapter 2, graphene oxide (GO-)-immobilized titanium dioxide (TiO₂) was developed to efficiently carry and release antimicrobial drugs. Firstly, phenol-containing GO (GOTA) was immobilized onto the surfaces of TiO₂ through tyrosinase (Tyr)-catalyzed reaction (GOTA/TiO₂). Doxycycline hyclate (Dox) was then loaded onto GOTA/TiO₂ via non-covalent interactions between GO and Dox (Dox/GOTA/TiO₂), including electrostatic interaction, π-π stacking, hydrophobic interaction, and hydrogen bonds. The amount of loaded drug was able to be controlled, reaching a maximum of 36 µg/cm2. In vitro experiments revealed that the sustained release of Dox from the TiO₂ surfaces continued for over 30 days. Dox/GOTA/TiO₂ exhibited superior antibacterial activity against both gram-negative Escherichia coli and gram-positive Staphylococcus aureus bacteria, without affecting the viability of human dermal fibroblasts. The obtained results indicated that GO-immobilized TiO₂ is an effective carrier for antimicrobial drug delivery to reduce implant-associated infection through the synergistic antimicrobial effect of GO and the prescribed drugs. Chapter 3 described the development of the multifunctional surface with enhanced hemocompatibility and anti-inflammatory effects by combining the anticoagulant activity of heparin with the vasodilatory and anti-inflammatory properties of nitric oxide (NO). The co-immobilization of these two key molecules with distinct therapeutic effects is achieved by simultaneous conjugation of heparin (HT) and copper nanoparticles (Cu NPs), an NO-generating catalyst, via a simple tyrosinase (Tyr)-mediated reaction. The resulting immobilized surface showed long-term, stable and adjustable NO release. Importantly, the makeup of the material endows the surface with the ability to promote endothelialization and to inhibit coagulation, platelet activation, and smooth muscle cell proliferation. In addition, the HT/Cu NP co-immobilized surface-enhanced macrophage polarization towards the M2 phenotype in vitro, which can reduce the inflammatory response and improve the adaptation of implants in vivo. This study demonstrated a simple but efficient method of developing a multifunctional surface for blood-contacting devices. The obtained results demonstrated that tyrosinase-catalyzed reaction is an effective and facile method to functionalize the surface of various implantable devices. Besides, the synergistic effect of bioactive agents can significantly improve the achievement of the implantable medical devices
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Molecular Science and Technology > 4. Theses(Ph.D)
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