Publication Date

2016-04-13

Availability

Open access

Embargo Period

2016-04-13

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Biomedical Engineering (Engineering)

Date of Defense

2016-03-25

First Committee Member

Weiyong Gu

Second Committee Member

Chun-Yuh Huang

Third Committee Member

Alicia R. Jackson

Fourth Committee Member

Fotios Andreopoulos

Fifth Committee Member

Mark D. Brown

Abstract

Intervertebral disc (IVD) is the largest avascular structure in the human body and its main function is to support mechanical loading and to provide the flexibility for the spine system. Degenerative disc disease (DDD) is related to low back pain which affects more than 600 million people worldwide. One of the challenges in modeling DDD is that the biological, mechanical, chemical, and electrical events in IVD are coupled at different levels. It is important to develop a numerical model to understand the biophysics and pathophysiology in IVD (a biological system). A multiscale and multi-physics model was developed based on a cell-activity-coupled mechano-electrochemical continuum mixture theory. In this model, the phenomena at the solute (or solvent) level (e.g., diffusion and/or reaction of ions, nutrients, growth factors, and interstitial fluid), cellular level (e.g., cell metabolism and viability), and tissue level (e.g., disc volume and shape) are accounted for. The model also includes the interactions among biological (cell activity), chemical [osmolarity, pH, extracellular matrix (ECM) synthesis and degradation], electrical (charges on ECM and solutes), and mechanical (loading and tissue swelling) events in the IVD. Numerical results were obtained by solving a dozen of partial differential equations using a finite element method. This model has been successfully used to simulate the degenerative progression of the IVD (up to 55 years) due to poor nutrition supply. The predicted distributions of water content in the IVD were consistent with those from direct measurements published in the literature. This result was also consistent with those observed in MRI images of IVDs in human patients. The model was also used to study kinetics of charged antibiotics (for treating disc infections) and effects of dynamic loading on cell viability (for preventing degeneration) in the IVD. The model has also been used to investigate the long-term efficacy (up to 10 years) of cell therapies for disc repair (i.e., in silico clinical trials). This model can be used not only to provide insights into the mechanisms of disc degeneration, but also to develop new diagnostic tools and to optimize new therapeutic strategies for degenerated discs.

Keywords

Biomechanics; Mechanobiology; Continuum Mixture Theory; Finite Element Model; Intervertebral Disc Degeneration; Disc Repair

Share

COinS