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CHAPTER 5: GENERAL CONCLUSION
Study 1:
The present study demonstrated that 1.167 and 0.117 mg/ml of rhBMP-2 with ACS as
the carrier induced ectopic bone formation in 4 weeks. The in vivo findings, on the other
hand, confirmed the ability of ACS to retain rhBMP-2, support the newly formed bone,
and show a good biodegradation rate. However, bone formation was not observed with
0.039 mg/ml of rhBMP-2. Moreover, rhBMP-2 was found to be osteogenic even at onetenth of recommended concentration, indicating the potential for clinical use at lower
concentrations. Future research might focus on the development of release control
delivery vehicles. Combining rhBMP-2 with various bone grafting materials improves
mechanical strength and osteogenic potential while using lower rhBMP-2 concentrations.
Study 2:
This study represents a further development in the method used for Study 1. This
demonstrated the same concentration of rhBMP-2 used in Study 1(1.167 mg/ml), which
combined with phosphorylated pullulan and β-tricalcium phosphate. These composite
scaffolds were implanted in the ectopic sites of rat model with 2 weeks of observation.
We found that the mixture of 20101B (PPL1) (600,000 MW of PPL) and 20101D (PPL2)
(combined 600,000 MW and 1,000,000 MW of PPL) with a ratio of 1-5 is the optimum
molecular weight of PPL, which can induce greater bone formation as well as a higher
biological degradability of PPL. We concluded that this composite can be considered a
potentially promising material in the field of bone regeneration. In the future experiment,
the optimum doses of BMP-2 and the optimum amount of β-tricalcium that induce greater
bone formation with no side effects might be determined.
Study 3:
This study also reflects an advancement in the approach utilized in Study 1 and 2, in
which four different rhBMP-2 doses combined with phosphorylated pullulan and βtricalcium phosphate. However, we synthesized BMP/PPL/β-TCP composite scaffolds of
low BMP-2 doses to find a composite of higher osteogenic properties with lower BMP-2
55
dose. Our conclusion is that BPT2 scaffolds induced greater bone formation than BC1
implant material with only one-tenth of recommended doses. These newly developed
scaffolds can be regarded as a very promising material in bone regeneration. Further
studies are required to examine the adhesive behavior of this recently developed
composite scaffold.
Acknowledgments
The completion of this work would not have been possible without the god all mighty
support and guidance. I would like to express my sincere gratitude to my Ph.D. thesis
advisor Prof. Tsutomu SUGAYA for his continuous support and guidance in my Ph.D.
study, research, and clinical training for his patience, motivation, enthusiasm, and
knowledge. A debt of gratitude is also owed to Prof. Norio Amitsuka, Prof.Yasuhiro
Yoshida, and Dr. Kumiko Yoshihara for helping us in materials and technical works.
I wish to extend my sincere appreciation to Dr. Yasuhiro Morimoto and Dr. Hirofumi
MIYAJI and all the members of the department for their assistance and support.
My gratitude extends to the Embassy of Saudi Arabia - Cultural Office in Tokyo and Jouf
University for sponsoring my education and training, as well as for their endless support
over the last four years. Finally, I thank my parents, my wife, and my whole family
members, for their patience, guidance, and support during my Ph.D. journey.
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