Use of polymer-peptide system to deliver cells for intervertebral disc regeneration

Abstract Low back pain affects millions of Americans and causes $100 billion socioeconomic loss annually. One of the prominent risk factors is intervertebral disc degeneration. Current treatments are palliative for relieving pain without restoring disc biology or biomechanics. Pain recurrence is common. Spinal fusion is popular, but it is limited by high failure rate (up to 30%) while predisposes adjacent discs to expedited deterioration. Immerging cell therapy is being actively developed with potential to halt or reverse disc degeneration while ameliorates symptoms. A recent invention of a peptide functionalized self-crosslinking polymer hydrogel has displayed initial evidence for improving the treatment effect of the therapeutic mesenchymal stromal cells on disc degeneration. To further investigate the therapeutic use of the new hydrogel material as a cell carrier, the present study is designed to investigate the working mechanism and optimize the formulation for treating disc degeneration and related low back pain. Accordingly there specific studies are designed targeting to investigate the impact of the hydrogel on the phenotype stability and cytokine release of the therapeutic donor cells, biosynthesis changes of host disc cells in response to the delivered donor cells, and therapeutic effect on the degenerated discs in the experimental animals using multiple in vitro and in vivo models. The present study will generate solid proof of concept data for the therapeutic use of the peptide-functionalized hydrogel in delivery of therapeutic cells for disc degeneration and related low back pain treatment.Project Narrative Chronic low back pain is a leading cause of disability worldwide affecting 13.1% of US adults aged 20-69 years old incurring a total cost of andgt;$100 billion per year. Current standard of cares aim to relieve symptoms but cannot resolve the underlying causes. Restoring the intervertebral disc (IVD) health by biomaterial assisted delivery of therapeutic cells emerges as a new potential solution for treating early to moderate symptomatic disc degeneration related low back pain.