Ph.D. Research Proposal - Synthesis and Characterization of an Enzymatically Resistant Biomimetic Aggrecan Glycopolymer
Date: May 11, 2010
Time: 9:30 AM
Location: Bossone Research Enterprise Center, Room: 709
Advisor: Michele Marcolongo, Ph.D.
Back pain is a prevalent, debilitating condition with between 30% and 40% of adults in the U.S. reporting to have experienced low back pain in the previous three months and an annual estimated cost of over $193 billion as reported in 2004. Of the various causes of low back pain, degenerative changes of the intervertebral disc (IVD) are a leading contributor to spinal fusion, a late stage surgical treatment for the stabilization of the spine. Intervertebral disc degeneration is accompanied by a loss of aggrecan in the inner nucleus pulposus (NP) region of the disc, resulting in a loss of charged chondroitin sulfate (CS) chains, and decreasing mechanical function of the NP. Degenerative changes in the NP are thought to precede damage to the outer annulus fibrosus (AF) region of the IVD where damage to the AF leads to disc herniation. A minimally invasive early interventional strategy that addresses the degenerative changes of the NP and restores NP mechanical function may reduce the need for traumatic and costly spinal fusion surgery and provide relief for those suffering from pain related to disc degeneration.
In this work I propose the fabrication of a biomimetic aggrecan macromolecule for the replacement of aggrecan lost in the NP as a result of aging and disc degeneration. The strategy for the fabrication of a hybrid bottle-brush structure (which mimics the ultrastructural organization of CS in aggrecan), with natural chondroitin sulfate bristles (bio) and polymeric backbone (synthetic) will be discussed. Natural CS was chosen in order to maintain the biological function of the biomimetic polymer while a synthetic polymeric backbone was chosen as it will provide enzymatic resistance. Both the “grafting-to” and “grafting-through” strategies of bottle-brush synthesis will be investigated. Preliminary data demonstrating the feasibility of applying these two methods to the fabrication of a CS bottle-brush will be presented and proposed functional and biological characterization of the resulting CS-glycopolymer will be discussed.
The Bossone Research Enterprise Center is located at the corner of 32nd and Market Streets.