S-Space College of Engineering/Engineering Practice School (공과대학/대학원) Program in Bioengineering (협동과정-바이오엔지니어링전공) Theses (Ph.D. / Sc.D._협동과정-바이오엔지니어링전공)
SURFACE COATING OF IMPLANTABLE MEDICAL DEVICES ADDING THERAPEUTIC FUNCTIONALITY
치료 기능 부가를 위한 이식형 의료기기의 표면 코팅 연구
- 공과대학 협동과정 바이오엔지니어링전공
- Issue Date
- 서울대학교 대학원
- 학위논문 (박사)-- 서울대학교 대학원 : 협동과정 바이오엔지니어링전공, 2015. 2. 최영빈.
- This dissertation is described with material, design, fabrication and analysis/evaluation for surface coating of implantable medical devices, i.e., bone fixation systems and silicone implants, in order to add the therapeutic functionality. Even though the implantable medical devices have been widely developed and used in the clinical field, these still have drawbacks associated with lack of therapeutic functionality. To solve these, we suggest a promising multifunctional medical device adding therapeutic functionality, maintaining intact functionality of the implantable medical device.
Firstly, in order to control the corrosion rate of magnesium (Mg), we coated the surface of magnesium (Mg) with a biodegradable polymer, polycaprolactone (PCL) and varied coating thickness in a reproducible manner using an automated apparatus designed to follow the widely-accepted dip-coating method. Herein, PCL served as a good permeation barrier owing to its hydrophobicity and slower degradation in biological fluid than Mg. As we increased the coating thickness from 0 to 13.31 ± 0.36 µm, the volume of hydrogen gas and amount of Mg ions, the indicators of Mg corrosion, decreased by almost half from 0.57 ml/cm2/day and 0.55 mg/day to 0.20 ml/cm2/day and 0.26 mg/day, respectively. Therefore, we demonstrated that the thicker coating could better hinder the water permeation to the Mg surface and thus, a corrosion rate could be reduced in this work.
Secondly, we prepared a bone plate enabled with local, sustained release of alendronate, which is a drug known to inhibit osteoclast-mediated bone resorption and also expedite bone-remodeling activity of osteoblasts. For this, we coated a bone plate already in clinical use (PLT-1031, Inion, Finland) with a blend of alendronate and a biocompatible polymer, azidobenzoic acid-modified chitosan (i.e., Az-CH) photo-crosslinked by UV irradiation. As we performed the in vitro drug release study, the drug was released from the coating at a rate of 4.03 μg/day for 63 days in a sustained manner. To examine the effect on bone regeneration, the plate was fixed on an 8 mm cranial critical size defect in living rats and a newly formed bone volume was quantitatively evaluated by micro-computed tomography (micro-CT) at schedule times for 8 weeks. At 8 week, the group implanted with the plate enabled with sustained delivery of alendronate showed a significantly higher volume of newly formed bone (52.78 ± 6.84 %) than the groups implanted with the plates without drug (23.6 ± 3.81 %) (p < 0.05). The plate enabled with alendronate delivery also exhibited good biocompatibility on H&E staining, which was comparable to the Inion plate already in clinical use. Therefore, we suggest that a bone plate enabled with local, sustained delivery of alendronate can be a promising system of a combined functionality of bone fixation and its expedited repair.
Lastly, we proposed the acute, local suppression of transforming growth factor beta (TGF-ß), a major profibrotic cytokine, to reduce fibrosis around silicone implants. To this end, we prepared silicone implants that were able to release tranilast, a TGF-ß inhibitor, in a sustained manner for 5 days or 15 days. We performed histologic and immunohistochemical analyses for 12 weeks after the implantation of the implants in living rats. The capsule thicknesses and collagen densities significantly decreased compared with those around the non-treated silicone implants. Notably, early suppression of TGF-ß affected the fibrogenesis that actually occurs at the late stage of wound healing. This change may be ascribed to the decrease in monocyte recruitment mediated by early TGF-ß during the acute inflammatory reaction. Thus, a significant decrease in differentiated macrophages was observed along with a decrease in the quantity of TGF-ß and fibroblasts during the subsequent inflammation stage
these changes led to a diminished fibrotic capsule formation.