Developing an Injectable Hydrogel System for Nucleus Pulposus Replacement

1
Developing an Injectable Hydrogel System for
Nucleus Pulposus Replacement

• Jeremy Griffin
• Mentor Jennifer Vernengo
• Advisor Dr. Tony Lowman
• Department of Chemical Engineering

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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
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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.
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The Intervertebral Disc
www.lieberson.com
www.lieberson.com
http//www.nlm.nih.gov 

• 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

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Degenerative Disk Disease (DDD)
www.spinecenteronline.com

• Caused by dehydration or damage of the
  nucleus pulposus

www.spineuniversity.com
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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

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DDD Treatments

• Conservative Treatments
• Pain Killers
• Physical Therapy / Exercise
• Bed Rest

www.brypix.com
www.rehabpub.com
fpb.cwru.edu
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Major DDD Treatments

• Surgical Interventions
• Discectomy
• Complete disc replacement
• Spinal Fusion

www.popsci.com
www.neurosurgerytoday.org
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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
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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
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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

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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

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

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Poly (ethylene glycol) Dimethacrylate

• PEGDM
• Copolymerization of NIPAAm and difunctional PEG
  yields branched copolymer

Branched PNIPAAm-PEGDM copolymer

NIPAAm
PEG Dimethacrylate
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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

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In-Vitro Swelling Study

• Monitor swelling ratio (Q) for up to 180 days in
  vitro
• 37º C phosphate buffer solution (pH7.4)

PEG rich copolymers
Swelling ratio, q
PNIPAAM homopolymer
Time (days)
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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
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Acknowledgements

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

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• Questions ?