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. Public Health Relevance Statement 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 >$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.
Project Terms: Adult ; 21+ years old ; Adult Human ; adulthood ; Affect ; Pain management ; Pain Control ; Pain Therapy ; pain treatment ; Animal Experimentation ; Animal Experimental Use ; Animal Research ; Animals ; Anti-Inflammatory Agents ; Anti-Inflammatories ; Anti-inflammatory ; Antiinflammatories ; Antiinflammatory Agents ; antiinflammatory ; Back ; Dorsum ; Biocompatible Materials ; Biomaterials ; biological material ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Biology ; Biomechanics ; biomechanical ; Bone Marrow ; Bone Marrow Reticuloendothelial System ; Cell Differentiation process ; Cell Differentiation ; Cell Nucleus ; Nucleus ; Cell physiology ; Cell Function ; Cell Process ; Cellular Function ; Cellular Physiology ; Cellular Process ; Subcellular Process ; Cell Survival ; Cell Viability ; Cells ; Cell Body ; Clinical Research ; Clinical Study ; Environment ; Extracellular Matrix ; Cell-Extracellular Matrix ; ECM ; Growth ; Generalized Growth ; Tissue Growth ; ontogeny ; Health ; Homeostasis ; Autoregulation ; Physiological Homeostasis ; Human ; Modern Man ; Human Engineering ; In Vitro ; Inflammation ; Intervertebral disc structure ; Intervertebral Disk ; Laminin ; Glycoprotein GP-2 ; Low Back Pain ; Low Back Ache ; Low Backache ; Lumbago ; Magnetic Resonance Imaging ; MR Imaging ; MR Tomography ; MRI ; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance ; NMR Imaging ; NMR Tomography ; Nuclear Magnetic Resonance Imaging ; Zeugmatography ; Methods ; Neck ; Pain ; Painful ; Palliative Care ; Palliative Therapy ; Palliative Treatment ; comfort care ; Legal patent ; Patents ; Peptides ; Phenotype ; Polymers ; Production ; Proteins ; Rattus ; Common Rat Strains ; Rat ; Rats Mammals ; Recurrence ; Recurrent ; Risk ; Risk Factors ; Spinal Fusion ; Spondylosyndeses ; Vertebral column ; Spinal Column ; Spine ; backbone ; Technology ; Transplantation ; transplant ; Roentgen Rays ; X-Radiation ; X-Ray Radiation ; X-ray ; Xray ; cytokine ; Injectable ; Outcome Measure ; Caring ; intervertebral disk degeneration ; Intervertebral Disc Degenerative Disease ; Intervertebral Disc Degenerative Disorder ; degenerated intervertebral disc ; degenerative disc disease ; disc degeneration ; Cell Density ; base ; crosslink ; cross-link ; improved ; Solid ; Encapsulated ; Phase ; Histologic ; Histologically ; Adolescent ; Adolescent Youth ; juvenile ; juvenile human ; Cell Transplantation ; Anabolism ; biosynthesis ; Serum ; Blood Serum ; disability ; Failure ; Functional disorder ; Dysfunction ; Physiopathology ; pathophysiology ; Coculture Techniques ; Co-culture ; Cocultivation ; Coculture ; chemokine ; Chemotactic Cytokines ; Homologous Chemotactic Cytokines ; Intercrines ; SIS cytokines ; chemoattractant cytokine ; cell mediated therapies ; cell-based therapeutic ; cell-based therapy ; cellular therapy ; Cell Therapy ; Therapeutic ; Inflammatory ; Reporter ; Autologous ; cell type ; System ; 3-D ; 3D ; three dimensional ; 3-Dimensional ; Height ; interest ; American ; biocompatibility ; biomaterial compatibility ; Protein Cleavage ; Proteolysis ; success ; Hydrogels ; Immunomodulation ; immune modulation ; immune regulation ; immunologic reactivity control ; immunomodulatory ; immunoregulatory ; immunoregulation ; novel ; Deterioration ; Modeling ; response ; nucleus pulposus ; Therapeutic Uses ; Hydration ; Hydration status ; Dose ; Data ; in vivo ; in vivo Model ; Small Business Technology Transfer Research ; STTR ; Pathologic ; socioeconomics ; socio-economic ; socio-economically ; socioeconomically ; Therapeutic Effect ; Behavioral ; pre-clinical ; preclinical ; cost ; design ; designing ; Outcome ; Chronic low back pain ; aged ; treatment effect ; effective therapy ; effective treatment ; disc regeneration ; regenerate disc tissue ; microCT ; X-ray microtomography ; Xray microtomography ; micro CT ; micro computed tomography ; microtomography ; invention ; Formulation ; reduce symptoms ; alleviate symptom ; ameliorating symptom ; decrease symptom ; fewer symptoms ; relieves symptoms ; symptom alleviation ; symptom reduction ; symptom relief ; Injections ; pain relief ; relieve pain ; mesenchymal stromal cell ; post-transplant ; post-transplantation ; posttransplant ; posttransplantation ;
