240 likes | 512 Views
Developing an Injectable Hydrogel System for Nucleus Pulposus Replacement. Jeremy Griffin Mentor: Jennifer Vernengo Advisor: Dr. Tony Lowman Department of Chemical Engineering. The Issue. Over 5 million Americans suffer from lower back pain 1
E N D
Developing an Injectable Hydrogel System for Nucleus Pulposus Replacement Jeremy Griffin Mentor: Jennifer Vernengo Advisor: Dr. Tony Lowman Department of Chemical Engineering
The Issue • Over 5 million Americans suffer from lower back pain1 • At least four out of five adults will experience lower back pain2 • Lower back pain is the leading cause of lost workdays in the US1 www.nohochiro.com [1] MedPro Month, 1998. VIII(1). [2] www.spine-health.com
The Issue • Lower back pain treatment and compensation costs: • $50 billion in the US • £12 billion in the United Kingdom2 • 75% of lower back pain is due to intervertebral disc degeneration in the lumbar region of the spine1 www.lowbackpain.com [1] MedPro Month, 1998. VIII(1). [2] Bibby, S. R. S., D.A. Jones, R.B. Lee , J. Yu , J.P.G. Urban, The Pathophysiology of theIntervertebral Disc. Joint Bone Spine, 2001. 68: p. 537-542.
The Intervertebral Disc www.lieberson.com www.lieberson.com http://www.nlm.nih.gov • The disctransfers compressive loads to the annulus in tension by exerting hydrostatic pressure on its inner surface • The Intervertebral Disc: • - Annulus fibrosis • - Nucleus Pulposus [High water content (80%)]
Degenerative Disk Disease (DDD) www.spinecenteronline.com • Caused by dehydration or damage of the nucleus pulposus www.spineuniversity.com
The Damaged Intervertebral Disc www.lieberson.com www.lieberson.com http://www.nlm.nih.gov www.neurosurgerytoday.org • No longer transfer loads to the annulus in tension • Compressive stress on annulus causes tears and cracks • Disc Herniation causes: • - Nerve impingement • - Inflammatory response
DDD Treatments • Conservative Treatments: • Pain Killers • Physical Therapy / Exercise • Bed Rest www.brypix.com www.rehabpub.com fpb.cwru.edu
Major DDD Treatments • Surgical Interventions: • Discectomy • Complete disc replacement • Spinal Fusion www.popsci.com www.neurosurgerytoday.org
Problems with DDD Treatments • No resolve to the cause of the back pain • Additional stresses on the surrounding discs and vertebrae causing degeneration • Healthy biomechanics are not restored • Invasive www.af.mil
Nucleus Pulposus Replacement • In early stages of disc degeneration the nucleus can be replaced with a synthetic material: • Less Invasive Procedure • Restores healthy biomechanical function Nucleus www.spineuniverse.com
Synthetic Nucleus Replacement • HYDROGELS • 3-D hydrated polymer network • Consistency similar to natural nucleus pulposus • Allow for the delivery of nutrition and removal of metabolism products
Injectable Nucleus Replacement • Synthetic material could be injected as a free flowing solution and solidify in situ • Advantages: • Potential to restore biomechanical function • Minimally invasive • Space filling
Thermo-responsive Polymers Two phases (polymer and solvent) Temperature Lower Critical Solution Temperature (LCST) Single phase (polymer solution) Concentration of polymer in solution
Poly (N-isopropylacrylamide) • PNIPAAm • Most widely studied thermo-responsive polymer because of the LCSTs proximity to the temperature of the human body 25oC 37oC Polymer chains
Direction of this Research • PNIPAAm homopolymer: • Holds limited water at 37º C(hydrophobic) • Lacks elasticity • Tailor water content and mechanical properties of precipitated phase: • Create branched copolymers with hydrophilic component
Poly (ethylene glycol) Dimethacrylate • PEGDM • Copolymerization of NIPAAm and difunctional PEG yields branched copolymer Branched PNIPAAm-PEGDM copolymer + NIPAAm PEG Dimethacrylate
Differential Scanning Calorimetry (DSC) • DSC defines the range of LCSTs • Hydrophilic component hinders dehydration and mobility of chains • LCST should increase with increasing PEGDM content
In-Vitro Swelling Study • Monitor swelling ratio (Q) for up to 180 days in vitro • 37º C phosphate buffer solution (pH=7.4) PEG rich copolymers Swelling ratio, q PNIPAAM homopolymer Time (days)
Unconfined Compressive Modulus • Instron mechanical testing system (100 % / minute) • Maintain modulus in suitable range • More covalent bonds (PEG) between copolymer chains increases the stiffness techunix.technion.ac.il
Acknowledgements • Jennifer Vernengo • Dr. Tony Lowman • All Members of the Biomaterials and Drug Delivery Lab