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BIOMATERIAL SYSTEMS WITH PERSISTENT GROWTH FACTOR GRADIENTS IN VIVO FOR TISSUE ENGINEERING APPLICATIONS
Title
BIOMATERIAL SYSTEMS WITH PERSISTENT GROWTH FACTOR GRADIENTS IN VIVO FOR TISSUE ENGINEERING APPLICATIONS
Creator
Akar, Banu
Date
2016, 2016-12
Description
Tissue engineering aims to develop strategies for the replacement of damaged, injured or missing tissues with biologically compatible...
Show moreTissue engineering aims to develop strategies for the replacement of damaged, injured or missing tissues with biologically compatible substitutes such as bioengineered tissues. However, generating tissues of su cient volume for clinical application requires the formation of stable and extensive vasculature within the tissue constructs. The overall goal of this work is to enhance vascularization using a gradient biomaterial system and apply this research to engineering vascularized bone of clinical size. First, a method was developed to create persistent growth factor gradients with an adjustable gradient magnitude in vivo. This method generated persistent gradients of platelet-derived growth factor (PDGF-BB) within brin/poly (ethylene glycol) (PEG) sca olds. The presence of a growth factor gradient within the system was veri ed in vivo using near-infrared imaging. Also, a computational model was developed to investigate gradient characteristics within the system. Gradient properties can be controlled by varying the degradation rate of the gradient layer components or dose of PDGF-BB delivered. The angiogenic potential of gradient sca olds was tested in rodents using a subcutaneous implantation model. The depth of tissue invasion and density of blood vessels formed in response to the biomaterial increased with dose of the growth factor. The gradient biomaterial system allows formation of persistent gradients that can be in uenced by biomaterial characteristics, and enhances vascularization. Therefore, this biomaterial system can be used for tissue engineering applications. Second, the brin/PEG-based sca olds were modi ed to be degradable via hydrolysis and to include bioactive ceramic particles (hydroxyapatite and -tri-calcium phosphate). Characteristics of the hydrogel ceramic composites were investigated in vitro and in vivo. The presence of ceramic particles extended degradation time of thehydrogels in vitro and in vivo. Hydrogel ceramic composites were tested in a rodent cranial defect model and enhanced bone tissue regeneration. Third, strategies developed from the previous studies were combined to prepare ceramic supplemented gradient sca olds for bone tissue engineering applications. A gradient layer was applied to the hydrogel-ceramic composites and bone tissue response was evaluated in a periosteum guided large animal model. Ceramic supplemented gradient sca olds augmented vascularization and bone regeneration in vivo. In conclusion, a biomaterial system with persistent growth factor gradients was developed and enhanced vascularization and bone regeneration in vivo. This system holds a great potential for tissue engineering applications.
Ph.D. in Biomedical Engineering, December 2016
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