Date of Completion

4-28-2017

Embargo Period

4-28-2017

Keywords

alginate, hydrogel, bone tissue regeneration, 3D printing

Major Advisor

Mei Wei

Associate Advisor

Anson Ma

Associate Advisor

Kelly Burke

Associate Advisor

Wendy Vanden Berg-Foels

Associate Advisor

Harold Brody

Field of Study

Materials Science

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Bone tissue engineering is employed to help enhance regeneration of bone tissue that may have difficulty of achieving sufficient healing on its own. As bones tend to break in irregular manners, methods to produce engineered scaffolds more closely fitting the geometry of the defective tissue are desirable. Current techniques to produce engineered bone tissue constructs result in stiff, rigid scaffolds with limited plasticity and ability to form irregular architectures. Additionally, processing methods limit the feasibility to uniformly incorporate live cells into the scaffolds for enhanced uniform healing. The use of hydrogel materials for bone tissue engineering has gained interest due to their high water content and interwoven structure mimicking that of the natural extracellular matrix, rendering them favorable for live cell incorporation. Alginate is a hydrogel with materials properties allowing manipulation in a variety of ways for numerous applications, including injectable fillers, 3D printing, drug and growth factor delivery, cell encapsulation and many more.

In this work, the gelation properties of a series of alginate hydrogel formulations were thoroughly studied and control of the gelation rate was established by varying component concentrations. An optimal hydrogel system was developed with a gelation time appropriate in a surgical setting and composition capable of aiding in new bone formation, confirmed through various characterization techniques. A systematic investigation was then conducted using the knowledge gained to determine the feasibility of their use in 3D printing. As a result, an alginate-polyvinyl alcohol-hydroxyapatite formulation was developed with optimal rheological properties allowing encapsulation of MC3T3 cells and 3D bioprinting of scaffolds with high shape fidelity and cell viability. Degradation studies showed the scaffolds maintained sufficient mechanical stability to support cell life in culture. In vitro evaluations were then conducted to determine the capacity of the formulations to support cell viability and promote cell proliferation. A synergistic effect was discovered, highlighting the need for both sufficient cell adhesion modalities in the matrix and appropriate scaffold mechanical rigidity.

Thus, the development of these alginate hydrogel systems can provide more personalized treatment options for bone repair with potential to enhance bone tissue regeneration.

Download
COinS