ORCID Identifier(s)

0000-0001-9775-3612

Graduation Semester and Year

2017

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering

Department

Bioengineering

First Advisor

Pranesh B. Aswath

Abstract

The advances in bone tissue engineering search for a biomaterial that could efficiently and gradually replace the bone while the new tissue grows through the implanted structure. However, due to limitations mainly related to mechanical properties and challenges, such as the balance between tissue regeneration and material degradation, the coating of well-known inert materials still has been used in orthopedics and dental clinical practices. Bone defects are commonly related to deleterious oxidative stress induced by low oxygen levels and inflammation. Toxic oxidative stress can impair damaged tissue healing due to inhibiting new blood vessels and new bone formation. The interaction between this hostile environment and implanted materials have been neglected, and the use of materials that can reduce oxidative stress to a physiological levels could enhance new tissue formation, reducing healing time and preventing material’s loosening and failure. Based on findings from our group’s previous study, we identified that ionic silicon plays a significant role on reduction of reactive oxygen species by upregulating superoxidase dismutase1 (SOD1), which is an important antioxidant enzyme. Another study demonstrated that mesoporous silica could enhance angiogenesis by upregulating hypoxic inducible growth factor (HIF-1α). For present research, we hypothesized that implants coated with amorphous silica by plasma enhanced chemical vapor deposition (PECVD) method could enhance endothelial cells angiogenesis under toxic oxidative stress condition. Moreover, we tested the hypothesis that the PECVD coating implants could enhance angiogenesis and reduce oxidative stress in an adult rat’s critical size calvarial defects. In order to test our hypothesis, we investigated (in vitro), and under normal condition, the effect of the ionic silicon and/or the amorphous silica PECVD coating materials on the endothelial cells viability, proliferation, migration, capillary tubule formation, matrix deposition, angiogenic markers and antioxidant enzymes. An In vivo experiment was also conducted in a rat’s critical size calvarial defect. And angiogenic and oxidative markers were measured in histological sections and serum. Firstly, we demonstrated that ionic silicon can recover the HUVECs’ viability under toxic oxidative stress conditions by reducing cell death and upregulating HIF-1α, VEGFA, and vascular endothelial growth factor receptor 2 (VEGFR-2). Secondly, we showed that PECVD coating amorphous silica based implants incorporated with nitrogen and phosphorus enhanced endothelial cells angiogenesis, increasing matrix deposition, cell migration, capillary tube formation, and gene expression of angiogenic markers and antioxidant enzymes. Third, we verified angiogenesis improvement on HUVECs under oxidative stress by preventing cell death, enhancing matrix deposition and upregulating the expression of angiopoietin-1 and antioxidant enzymes. Lastly, in vivo experiment corroborated with these findings and demonstrated enhancement in angiogenesis and reduction of oxidative stress. In conclusion, our findings support the use of PECVD coating amorphous silica-based implants applied in large bone defects due to its antioxidant and proangiogenic effect.

Keywords

Amorphous silica, Angiogenesis, Antioxidant

Disciplines

Biomedical Engineering and Bioengineering | Engineering

Comments

Degree granted by The University of Texas at Arlington

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