developing an injectable hydrogel system for nucleus pulposus replacement jeremy griffin mentor:...

Developing an Developing an Injectable Hydrogel Injectable Hydrogel System for Nucleus System for Nucleus

Pulposus ReplacementPulposus 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). [2] www.spine-health.com

www.nohochiro.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

[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

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

Degenerative Disk Disease (DDD)

www.spineuniversity.com

www.spinecenteronline.com

• Caused by dehydration or damage of the nucleus pulposus

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

DDD Treatments

• Conservative Treatments:

Pain Killers

Physical Therapy / Exercise

Bed Rest

www.brypix.com www.rehabpub.com fpb.cwru.edu

www.popsci.com www.neurosurgerytoday.org

Major DDD Treatments

• Surgical Interventions:

Discectomy

Complete disc replacement

Spinal Fusion

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

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

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

• 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

Thermo-responsive Polymers

Concentration of polymer in solution

Tem

pera

ture

Two phases

(polymer and solvent)

Single phase (polymer solution)

Lower Critical Solution

Temperature (LCST)

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

Injectable Nucleus Replacement

• 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

Poly (ethylene glycol) Dimethacrylate

• PEGDM

Copolymerization of NIPAAm and difunctional PEG yields branched copolymer

Branched PNIPAAm-PEGDM copolymer

NIPAAmPEG

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 StudyS

wel

lin

g r

atio

, 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)

Representative Stress-Strain Curve for PNIPAAM-PEGDM Copolymer Hydrogel

0

0.01

0.02

0.03

0.04

0.05

0.06

0.07

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7

Strain (mm/mm)

Co

mp

res

siv

e S

tre

ss

(M

Pa

)

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

Questions ?