Graduation Semester and Year

2012

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Materials Science and Engineering

Department

Materials Science and Engineering

First Advisor

Jian Yang

Abstract

Tissue adhesives are increasingly gaining more popularity in various areas of biomedical applications. They are utilized as surgical adhesives, as a replacement or adjunct to conventional wound closure and bleeding control techniques such as suturing, as well as in other applications such as tissue engineering and drug delivery.Unfortunately, the existing surgical adhesives are not ideal for wet tissue adhesion required in many surgeries such as those for internal organs. Developing surgical adhesives with strong wet tissue adhesion, controlled degradability and mechanical properties, and excellent biocompatibility has been a significant challenge. Herein, learning from nature, we report a one-step synthesis of a novel family of injectable citrate-based mussel-inspired bioadhesives (iCMBAs) for surgical use. Within the formulations investigated, iCMBAs showed 2.5-8.0 folds stronger wet tissue adhesion strength over the clinically used fibrin glue (39 to 123 kPa for iCMBAs vs. 15 kPa for fibrin glue), demonstrated controlled degradability and tissue-like elastomeric mechanical properties, and exhibited excellent cyto/tissue-compatibility both in vitro and in vivo. iCMBAs were able to stop bleeding instantly and suturelessly, and close wounds (2 cm long × 0.5 cm deep) created on the back of Sprague-Dawley rats. Equally important, the new bioadhesives facilitated wound healing, and were completely degraded and absorbed without eliciting significant inflammatory response. Our results support that iCMBA technology is highly translational and could have broad impact on surgeries where surgical tissue adhesives, sealants, and hemostatic agents are used. In the second part of this work, iCMBAs application in tissue engineering was also investigated by developing a new injectable in-situ crosslinkable bone composite based on iCMBA-hydroxyapatite (HA) with tunable set time, biodegradability, and excellent in vitro cyto-compatibility. The iCMBA-HA composites induced in vitro mineralization and differentiation of preosteoblast cells to osteobalsts. In vivo test showed that iCMBA-HA composite accelerated the bone repair and new bone tissue formation when injected to the region of a comminuted fracture in a New Zealand rabbit model.iCMBAs were also found to be pH sensitive polymers, from which we developed a new pH-responsive hydrogel for application in stimuli-responsive controlled drug delivery systems (CDDS). The controllable swelling ratio and degradation of pH-sensitive iCMBA hydrogels render them suitable for applications such as delivery of drugs and biological molecules to lower gastrointestinal tract through oral administration. In addition, iCMBA can be used to not only close wounds, but also prepare drug-eluting hydrogels, which can sense and release drugs, e.g. anti-infectives, upon an increase in local pH due to worsening wound condition. iCMBA's tunable swelling and degradation, and cyto/tissue-compatibility make them a suitable candidate for this type of applications. In addition, we successfully fabricated iCMBA nanoparticles through a facile and safe technique, which can earn additional advantage for iCMBA nanogels as a novel pH-responsive drug delivery system.

Disciplines

Engineering | Materials Science and Engineering

Comments

Degree granted by The University of Texas at Arlington

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