S-Space College of Engineering/Engineering Practice School (공과대학/대학원) Dept. of Material Science and Engineering (재료공학부) Theses (Ph.D. / Sc.D._재료공학부)
Biomedical Titanium Implants Eluting Growth Factors
성장인자 장기방출형 의료용 티타늄 임플란트
- 공과대학 재료공학부
- Issue Date
- 서울대학교 대학원
- 학위논문 (박사)-- 서울대학교 대학원 : 재료공학부, 2013. 2. 김현이.
- Titanium (Ti) is one of the most frequently used biomaterial in the orthopedic and dental field due to their outstanding mechanical properties, chemical stability, and good biocompatibility. Despite these excellent properties and extensive usage in the medical field, titanium has limited bone integrative properties prolonged when exposed in physiological environment. As attempts to overcome this problem, researchers in the past decade have utilized biomolecules such as growth factors to coat the implant to enhance the bone and implant integration. One of the most commonly researched biomolecule is bone Morphogenetic Protein-2 (BMP-2). BMP-2 is an osteogenic protein that plays an important role in physiological functions such as embryonic development, generation of the central nervous system, and tissue repair. However, BMP-2 coated on Ti surfaces often results in rapid diffusion, denaturation and degradation. Therefore a novel BMP-2 carrier is needed to release BMP-2 for an extended period.
In the first study, Ti scaffolds were fabricated through a novel freeze casting method for use as Ti-based BMP-2 carriers. Dynamic freeze casting was used to produce porous Ti scaffolds with a uniform porous structure and good ductility. Ti/camphene slurries with various initial Ti contents (15, 20, and 25 vol%) were frozen at 44 °C in rotation, in which camphene crystal growth occurred extensively and uniform Ti walls were constructed. All fabricated samples showed spherical pores surrounded by dense Ti walls that were uniformly formed. The porosity decreased from 71 to 52 % with an increase in Ti content from 15 to 25 vol%, whereas the pore size decreased from 362 to 95 m. The compressive strength and stiffness increased considerably from 57 to 183 MPa and from 1.3 to 5.0 GPa, respectively. These results indicate that dynamic freeze casting is quite useful for producing porous Ti scaffolds with a uniform pore structure which has a potential for use as bone scaffold materials.
In the second study, Ti scaffolds fabricated by dynamic freeze casting were studied for their abilities to load and deliver growth factor such as BMP-2. Porous Ti scaffold was soaked in a solution containing BMP-2 in a vacuum state and was densified to control the release rate of BMP-2. By SEM observation, porosity and pore size of the densified Ti decreased with an increase in pressure. The tensile strengths of the densified scaffolds range from 44 to 164 MPa, which are similar to the mechanical properties of the human cortical bone. GFP was used to analyze the growth factor loading capability of the densified Ti samples. Through CLSM imaging, the densified titanium samples showed prolonged release of the loaded GFP which were slowly released from the internal pores up to 16 weeks. The release of BMP-2 from the BMP-2-embedded densified Ti was relatively steady in which considerable amounts of BMP-2 were released even after 20 weeks. The in vitro cellular responses of the MC3T3-E1 pre-osteoblasts were examined using a cell attachment, a cell proliferation assay and an alkaline phosphatase (ALP) assay, and these results demonstrated that the BMP-2 embedded densified Ti also enhanced cell adhesion, proliferation and differentiation levels. Additional cell tests were performed to verify the functionality of BMP-2 after 8 weeks of release. To examine the potential of BMP-2-embedded densified Ti as a growth factor carrier, in vivo animal test was conducted using a rabbit calvarial defect model. The micro-CT images of BMP-2-embedded densified Ti ring implant that was implanted for 6 weeks showed better integration with the calvaria on the surface compared to the as-received Ti implant. Moreover, better cell ingrowth was observed on the densified sample compared to that of the control sample. The new bone volume of the densified samples was approximately 1.5 times greater than that of the as-received control sample. These results suggest that that BMP-2 embedded densified Ti could be used as a potential candidate for the growth factor delivery systems in the dental and orthopedic field.