1. Developing an Injectable Hydrogel System for Nucleus Pulposus Replacement Jeremy Griffin Mentor: Jennifer Vernengo Advisor: Dr. Tony Lowman Department of Chemical Engineering

2. The Issue Over 5 million Americans suffer from lower back pain 1 At least four out of five adults will experience lower back pain 2 Lower back pain is the leading cause of lost workdays in the US 1 [1] MedPro Month, 1998. VIII(1). [2] www.spine-health.com www.nohochiro.com

3. The Issue Lower back pain treatment and compensation costs: $50 billion in the US £12 billion in the United Kingdom 2 75% of lower back pain is due to intervertebral disc degeneration in the lumbar region of the spine 1 [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. www.lowbackpain.com

4. The Intervertebral Disc http://www.nlm.nih.gov www.lieberson.com The Intervertebral Disc: - Annulus fibrosis - Nucleus Pulposus [High water content (80%)] The disc transfers compressive loads to the annulus in tension by exerting hydrostatic pressure on its inner surface www.lieberson.com

5. Degenerative Disk Disease (DDD) www.spineuniversity.com www.spinecenteronline.com Caused by dehydration or damage of the nucleus pulposus

6. The Damaged Intervertebral Disc http://www.nlm.nih.gov www.lieberson.com No longer transfer loads to the annulus in tension Compressive stress on annulus causes tears and cracks Disc Herniation causes: - Nerve impingement - Inflammatory response www.neurosurgerytoday.org www.lieberson.com

7. DDD Treatments Conservative Treatments: Pain Killers Physical Therapy / Exercise Bed Rest www.brypix.comwww.rehabpub.comfpb.cwru.edu

8. www.popsci.comwww.neurosurgerytoday.org Major DDD Treatments Surgical Interventions: Discectomy Complete disc replacement Spinal Fusion

9. Problems with DDD Treatments No resolve to the cause of the back pain www.af.mil Invasive Healthy biomechanics are not restored Additional stresses on the surrounding discs and vertebrae causing degeneration

10. Nucleus Pulposus Replacement www.spineuniverse.com In early stages of disc degeneration the nucleus can be replaced with a synthetic material: Less Invasive Procedure Restores healthy biomechanical function Nucleus

11. Synthetic Nucleus Replacement 3-D hydrated polymer network Consistency similar to natural nucleus pulposus Allow for the delivery of nutrition and removal of metabolism products HYDROGELS

12. Synthetic material could be injected as a free flowing solution and solidify in situ Advantages: Potential to restore biomechanical function Minimally invasive Space filling Injectable Nucleus Replacement

13. Thermo-responsive Polymers Concentration of polymer in solution Temperature Two phases (polymer and solvent) Single phase (polymer solution) Lower Critical Solution Temperature (LCST)

14. Poly (N-isopropylacrylamide) PNIPAAm Most widely studied thermo-responsive polymer because of the LCSTs proximity to the temperature of the human body 25 o C 37 o C Polymer chains

15. Injectable Nucleus Replacement

16. 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 Direction of this Research

17. Poly (ethylene glycol) Dimethacrylate PEGDM Copolymerization of NIPAAm and difunctional PEG yields branched copolymer Branched PNIPAAm- PEGDM copolymer NIPAAm PEG Dimethacrylate +

18. 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

19. In-Vitro Swelling Study Swelling ratio, q PEG rich copolymers PNIPAAM homopolymer Time (days) Monitor swelling ratio (Q) for up to 180 days in vitro 37º C phosphate buffer solution (pH=7.4)

20. 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

21. Acknowledgements Jennifer Vernengo Dr. Tony Lowman All Members of the Biomaterials and Drug Delivery Lab

22. Questions ?