Developing an injectable hydrogel system for nucleus pulposus replacement
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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

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Developing an Injectable Hydrogel System for Nucleus Pulposus Replacement

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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

[1] MedPro Month, 1998. VIII(1).


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

[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 

  • 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)

  • Caused by dehydration or damage of the nucleus pulposus

The Damaged Intervertebral Disc

  • 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

Major DDD Treatments

  • Surgical Interventions:

    • Discectomy

    • Complete disc replacement

    • Spinal Fusion

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

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


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

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)


Lower Critical Solution Temperature (LCST)

Single phase (polymer solution)

Concentration of polymer in solution

Poly (N-isopropylacrylamide)


    • Most widely studied thermo-responsive polymer because of the LCSTs proximity to the temperature of the human body



Polymer chains

Injectable Nucleus Replacement

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


    • Copolymerization of NIPAAm and difunctional PEG yields branched copolymer

Branched PNIPAAm-PEGDM copolymer





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


  • Jennifer Vernengo

  • Dr. Tony Lowman

  • All Members of the Biomaterials and Drug Delivery Lab

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