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