Hydrogels for Medical · PDF fileHydrogels for Medical Applications Past, Present and Future Gavin Braithwaite Cambridge Polymer Group, Boston, MA

Hydrogels for Medical Applications Past, Present and Future

Gavin Braithwaite

Cambridge Polymer Group, Boston, MA

Biological hydrogels

• Hydrogels are everywhere in nature• Can be dynamic or permanent• Diverse usage but mostly water

Cambridge Polymer Group (2)Polymer and Plastics in Medical Devices, SF 2013Images: http://web.mechse.illinois.edu/research/ewoldt/research.html; www.scq.ubc.ca; www.naturalheightgrowth.com

What are hydrogels?

• Ferry– “…a substantially diluted system which exhibits no stead-state flow.”– Chemistry of the polymer, locked in place by “crosslinks” and supported

by water• Stabilization (crosslinks)

– Electrostatic (clays)– Associative (mucins and consumer gels)– Hydrogen bonded “crystals” (gelatin and PVA)– Chemical crosslinks (contact lenses)

Cambridge Polymer Group (3)Polymer and Plastics in Medical Devices, SF 2013Images: http://quick-dish.tablespoon.com

Chemically identical

Physically different

Why are they so important?

• Hydrogels are– Water filled (>80% in most cases)– Permeable– Viscoelastic– Lubricious – Hydrophilic– Chemically diverse– Environmentally sensitive– Allow solute transport– Multi-functional

Cambridge Polymer Group (4)Polymer and Plastics in Medical Devices, SF 2013Images: Bodugoz-Senturk

Production of hydrogels

• Controlled by chemistry of chain and method of crosslinking

• Chemical crosslinker

• Self-assembly– Dynamic and labile gels generally– Usually pronounced yield stress– Triggered by temperature or environment

Cambridge Polymer Group (5)Polymer and Plastics in Medical Devices, SF 2013Image:http://origin-ars.els-cdn.com/content/image/1-s2.0-S1748013209000905-gr2.jpg

Common chemistries

Cambridge Polymer Group (6)Polymer and Plastics in Medical Devices, SF 2013

• A snapshot of common biomedical systems– Poly(HEMA): poly(Hydroxyethyl methacrylate)

• Contact lenses, dressings, drug release– PEG: poly(ethylene glycol)

• Injectables, drug release, scaffolds– PVA: poly(vinyl alcohol)

• Contact lenses, nerve guides cartilage, wound dressings, reconstructive

– PVP: poly(vinyl pyrrolidone)• Wound dressings

– Poly(acrylamide)• Water “solidifiers”, tissue bulking, soil conditioner

• Other common hydrogels– Starch, agarose, pectin, gelatin, and many others

Past & current uses

• Industrial– Bulkhead seals– Waste clean-up

• Consumer– Hair-gel– Cosmetics

• Medical– Contact lenses– Drug release – Nerve guides– Coatings– Tissue bulking– Nucleus replacement

Cambridge Polymer Group (7)Polymer and Plastics in Medical Devices, SF 2013Images: www.mide.com; www.chemicalengineering.byu.edu

Where to next

• Current usage largely non-load bearing (even nucleus)– Drug release, scaffolds, guides, tissue bulking

• The body makes extensive use of hydrogels in the joint– Meniscus– Cartilage– Labrum– Intervertebral disc

• These joints readily compromised– Osteoarthritis

• 27M people in US– Trauma

• >800,000 meniscus surgeries annually• Accelerates degeneration• Associated with lesions

Cambridge Polymer Group (8)Polymer and Plastics in Medical Devices, SF 2013Image: http://soni2006.hubpages.com/hub/Advice-for-patients-suffering-from-osteoarthritis-both-knees

The trouble with the knee

• The human knee is a “simple” joint– Cylinder on flat– Contact forces 3-5x body weight– ~10 MPa normally

• 30 MPa (stair) up to 50 MPa (lunge)– Kinematics

• Rotation over 20°• Flexion up to 50°• Displacement 3-4 cm

– Velocities up to 0.6 m/s– Coefficient of friction <0.04

• Soft-tissues allow it to function– Also represent its weakness

Cambridge Polymer Group (9)Polymer and Plastics in Medical Devices, SF 2013Image: www.blenderartists.org, stemcelldoc.wordpress.com

How to (re)build a knee

• Soft-tissues have complex structure– Work as hybrid structures

• Cartilage– Properties change from surface to bulk to

transition to boney substrate– Provides unique shear response

• Meniscus– Cartilagenous structure supported by

radial hoops

Cambridge Polymer Group (10)Polymer and Plastics in Medical Devices, SF 2013Image: kneejointsurgery

Engineered (and testing) soft-tissue repair

• Problem:– Low friction– High load– Load distribution– Displacement/shear tolerant– Soft-tissue preserving

Cambridge Polymer Group (11)Polymer and Plastics in Medical Devices, SF 2013Image: kneejointsurgery

Cartilage Meniscus

Water content [%] 68-85 60-70

Collagen % 10-20 15-25

Proteoglycan [%] 5-10 1-2

Young’s modulus [MPa] 5-10

Tensile modulus [MPa] ~10 100-200

UTS [MPa] 2/5

Aggregate modulus [MPa] ~0.7 ~0.4

Permeability x 1015 [m4/N.s] ~4 ~1

Friction Coeff [ ] 0.1 0.08

Thickness [mm] 0.5-5 0-10

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Polymerization with crosslinker (PEG-DMA) and chains (PEG-MA)

Hydrolysis in methanol and KOH

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Cartilage mimicking hydrogel

• Cartilage properties in part due to PGs• Mimic structure with hydrolyzed PVAc hydrogel with dangling chains


Lubricity and Friction

• Low friction is a defining feature of cartilaginous joints– Impacted by disease level– Diseased synovial fluid loses lubricity

Cambridge Polymer Group (13)Polymer and Plastics in Medical Devices, SF 2013Image: Neu et al. 2010

0.000

0.100

0.200

0.300

0.400

0.500

0.600

0.000 0.020 0.040 0.060 0.080 0.100 0.120 0.140Contact Pressure [MPa]

CO

F

LB on CoCr in DILB on CoCr in BSnon-LB on CoCr in DInon-LB on CoCr in BS

Lubricity and Friction

• Correct structure generates superb lubricity


0

0.1

0.2

0.3

0.4

0.5

0.6

0.007 0.021 0.035 0.049

Coe

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ent o

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[ ]

Contact stress [MPa]

PVA freeze-thaw gelCPG PVA gelCPG modified PVA gelCartilage-cartilage

Reinforcement

Cambridge Polymer Group (15)Polymer and Plastics in Medical Devices, SF 2013Image: sciencedirect.com

Fiber wound

Simple compression (strain/strain)

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9

Stre

ss [M

Pa]

Strain [mm/mm]

no reinforcement PVA monofilament wound around outside

Mechanical properties


Issues

• Use of polymers in soft-solids raises its own problems• Permeability

– Elutables major concern– Reaction biproducts– Access for media

• Mechanical testing complex– Viscoelastic solid implies rates critical

• Environment important– Humidity, salinity, pH

• Wear– How does one measure wear?


Thank you

Cambridge Polymer Group is a contract research laboratory specializing in polymers and their applications. We provide outsourced research and development, consultation and failure analysis as well as routine analytical testing and custom test and instrumentation design.

Cambridge Polymer Group, Inc.56 Roland St., Suite 310Boston, MA 02129(617) 629-4400http://[email protected]


Documents

Hydrogels for Medical · PDF fileHydrogels for Medical Applications Past, Present and Future Gavin Braithwaite Cambridge Polymer Group, Boston, MA