Date of Award

10-2017

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biomedical and Chemical Engineering and Sciences

First Advisor

Vipuil Kishore

Second Advisor

James Brenner

Third Advisor

Michael Fenn

Fourth Advisor

Manolis Tomadakis

Abstract

Bone related diseases and disorders are a significant socioeconomic burden in the United States. Autografts and allografts are most commonly used for the treatment of bone defects and non-unions; however, they are associated with limitations such as donor site morbidity and immune rejection, respectively. Over the past few decades, bone tissue engineering (BTE) using scaffold and cells has garnered significant interest as an alternative method for the repair and regeneration of bone defects. Recreation of the tissue microenvironment via the development of biomimetic scaffolds that resemble the physicochemical aspects (i.e., composition, topography, stiffness) of native bone is a promising approach that has been previously shown to improve scaffold properties and augment cellular response. In this realm, collagen type I and bioactive glass (Bioglass 45S5 (BG); an osteostimulative glass-ceramic) have been combined in numerous studies to generate hybrid scaffolds that mimic the organic and inorganic matrix composition of native bone. However, most existing collagen – BG scaffolds are comprised of randomly oriented collagen fibers that do not mimic the anisotropic orientation of collagen fibers found in native bone. Development of a collagen-BG scaffold that recapitulates the highly aligned arrangement of collagen fibers can improve scaffold mechanical properties and provide topographical cues to direct cellular response via contact guidance. In this study, an isolelectric focusing based method was employed to synthesize BG-incorporated electrochemically aligned collagen (BG-ELAC) threads and the effect of BG incorporation on collagen aligment, mechanical properties, bone bioactivity, and cell-mediated mineralization was investigated. It was hypothesized that tissue level BG (~ 60 wt. %) can be incorporated within ELAC threads. Further, it was hypothesized that BG incorporation into ELAC threads will improve mechanical properties of ELAC, enhance bone bioactivity, and accelerate Saos-2 cell mediated mineralization. The results of this study indicated that tissue-level BG can be efficiently incorporated within ELAC threads without disturbing the alignment of collagen fibrils. BG incorporation significantly improved the ultimate tensile stress and tensile modulus of ELAC threads (p < 0.05). BG-ELAC threads showed strong evidence of in vitro bone bioactivity when conditioned with simulated body fluid. Finally, BG incorporation significantly enhanced Saos-2 cell mediated mineralization on ELAC threads. In conclusion, BG incorporation into ELAC threads is a viable strategy for the development of a functional scaffold for BTE applications.

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