Overall, our laboratory performs research to elucidate the role of mechanobiologic factors in degenerative disc disease and repair. Currently active research projects fall under four main categories:
1. Intervertebral disc mechanics
To understand how mechanical stress impacts disc health, the complex time-dependent mechanical function of disc subregions must be better understood. Using a combination of innovative methods to experimentally measure, test, and analyze the disc, we have been able to characterize transient changes in intradiscal pressure and stress distributions among subregions in our animal model. These can then be linked to outcome measures of degeneration in vivo. Part of these efforts have been facilitated through the development and use of a fiber optic pressure sensor with Dr. Miao Yu in Mechanical Engineering.
2. Intervertebral disc cell-ECM interactions
A synergistic component in cellular response to mechanical stress is the manner by which cells interact with the ECM. During degeneration, marked structural and biochemical changes occur in the disc matrix. Using collagen thin film technology developed by Anne Plant's group at NIST, we are exploring how cell behavior is altered by changes in the collagen substrate. Such understanding of the parallel evolution of tissue properties and cellular function will significantly impact treatment of degeneration and potentially tissue engineering efforts in the disc.
3. Intervertebral disc cellular engineering
Although bioengineering has traditionally dealt with engineering questions surrounding biological systems, the biotech industry has had much success in engineering metabolic processes using recombinant DNA techniques. Along that vein, we are utilizing RNA interference to knock down expression of specific genes that we believe play a critical role in the degenerative process. This allows us to address the functional significance of certain proteins in the degenerative cascade, as well as test hypotheses on potential therpeutic targets. While purely research-oriented, the findings could have possible translational impact in the future.
4. Mesenchymal stem cell mechanotransduction
While many groups are exploring the potential for using stem cells in tissue engineered constructs, the fundamental issues on how they will respond to a particular biochemical and biomechanical environment have not yet been fully explored. We are particularly interested in how mechanical signals are transduced to cells that have undergone chondrogenic differentiation, since these are the phenotypes of cells relevant to nucleus pulposus engineering. Using a combination of cell deformation, engineering analysis, and RNAi, we hope to gain a better understanding of how the pericellular matrix and its components contribute to mechanotransduction.
5. Cellular gravisensing in microgravity
When cells are placed in a weightless environment, they exhibit altered response and function. The highly adaptive processes driving these alterations may lead to a systemic imbalance for astronauts during long-term manned space exploration. A more thorough understanding of cellular gravisensing – and a cell’s interaction with its surrounding physical and chemical environment – may yield strategies for maintaining astronaut health and recovery. In pursuit of that goal, we augment conventional clinorotation capabilities with lab-on-chip microfluidics to perform dynamic, live-cell simulated microgravity assays. These assays will help piece together the underlying mechanisms and possible signaling pathways for gravisensing.