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Title: Engineered biomolecules with improved functionalities for bone tissue engineering
Author: Tian, Pinyuan
ISNI:       0000 0005 0732 5577
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2014
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Biomolecules such as bone growth factors, extracellular matrix proteins, bioactive factor-derived peptides, and other mineralisation-promoting proteins are gaining increasing attention in bone tissue engineering due to the fact that they can play an important role in cell attachment, growth, differentiation, and migration, and therefore be used to enhance bone formation and develop bone substitutes. This study is focused on the development of engineered biomolecules with improved functionality, and their combination with supporting matrix materials for bone tissue engineering applications. Two types of biomolecules are studied: The first are short peptides derived from the growth factor bone morphogenetic protein 7 (BMP-7), which induces bone regeneration, and regulates bone formation. The second is an engineered recombinant metalloenzyme E. coli alkaline phosphatase (E. coli ALP), which hydrolyses organic phosphate and generates the inorganic phosphate required for the mineralisation of hard tissue. Titanium (Ti) implants and polycaprolactone (PCL) scaffolds were used to incorporate these engineered biomolecules to verify the improvement of their functionality and biological efficiency. Results indicate that the BMP-7-derived peptides have a limited function and are not promising candidates for bone tissue engineering applications; while the mutant E. coli ALP shows superior activity compare to the wild-type ALP (nearly 25 times) and bovine ALP (more than 9 times), and is shown to be a promising factor to enhance bone formation. The activity of E. coli ALP can be affected by many factors including NaCl, lyophilisation, histidine, and imidazole. When the ALP is combined with either a Ti implant or an ALP/PCL scaffold, it demonstrates outstanding mineral-promoting ability, making it a potential candidate for bone tissue engineering applications. In conclusion, this study demonstrates the potential of engineering biomolecules with improved functionalities for bone tissue engineering applications.
Supervisor: Stevens, Molly Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral