Engineering Biomedical Materials From total joints to tissue sparing - PowerPoint PPT Presentation

Engineering Biomedical Materials From total joints to tissue sparing Dr. Gavin Braithwaite Cambridge Polymer Group, 56 Roland Street, Suite 310 Boston, MA 02129 CONFIDENTIAL Cambridge Polymer Group, I nc. Testing, Consultation, and Instrumentation for Polymeric Materials 7-17 Presentation (10/1/2010)

Engineering implants • Historical device development – Surgeon determines a need – Engineer provides design to meet primary requirements • Often from existing materials – Incremental improvement iterates towards success Product improvement Gen 4 Gen 3 Gen 2 Gen 1 Product lifecycle Issue determination 4/19/2011 2 Cambridge Polymer Group

Biology versus engineering • The human body is a finely tuned biomechanical structure – Meniscus and cartilage 4/19/2011 3 Cambridge Polymer Group Images: medicinenet.com, MMG, sensorprod.com

The human hip • Ball-and-socket joint • Normal gait complex motion – rotation, flexion, extension • Loads can be high – Walking 3x body weight – Stumbling 9x body weight • Critical for mobility and quality of life Ratner et al. 4/19/2011 4 Cambridge Polymer Group

What goes wrong • Osteoarthritis caused by loss of cartilage – Bone-on-bone contact – 65% of patients requiring surgery • Up to 1M replacements annually • Success rate at 10 years post-surgery is between 90-95% typically – Very good! 4/19/2011 5 Cambridge Polymer Group Images: hipresurfacing.info, wikipedia

Hip replacement • 1891 First human implant (cemented ivory) • 1940 first metal implant • Up until the 1960’s, hip fusion (arthrodesis) was the standard treatment for painful hip joints – Pain relief, but complete loss of mobility 4/19/2011 6 Cambridge Polymer Group Images: orthogate

Engineering a solution • Charnley (Manchester) – Introduced articulating artificial hip joints in the 1960s • First attempt – driven by perception of friction – Low-lubricity • PTFE – Poor wear – Small head • Low contact area – dislocations • Second attempt – Applied engineering material to surgical problem • Polyethylene plastic cog – Gold standard since 1960’s Image: Wikipedia 4/19/2011 7 Cambridge Polymer Group

The next generation • Issue: poor wear – Good toughness, but poor resistance to wear patterns – Erosion of material and osteolysis • Solution: crosslinking of the polymer Ionizing radiation – HXPE Crosslinks (X) – Lower wear rates Scissions (X) G(X)~3G(s) Crystalline lamellae Crosslinks Irradiate Residual Amorphous regions 4/19/2011 8 free radicals Cambridge Polymer Group

Crosslinked UHMWPE -700 Control 46mm head ( γ in N2) 50 mg/MC -600 Controls ( γ in N2) -500 28 mm 17mg/MC Weight Change (mg) -400 -300 22 mm 15mg/MC Control 32 mm ( γ in air) -200 31mg/MC -100 Highly Crosslinked 22-46 mm 0 100 0 5 10 15 20 25 30 Cycles (millions) 4/19/2011 9 Cambridge Polymer Group

Material enhancements • Issue: Radiation crosslinking generates free-radicals – Material oxidizes – Premature embrittlement • Solution: Crosslinking in inert atmosphere – Prevent oxidation during processing and storage – Long-term concerns due to in vivo oxidation Residual free radicals 4/19/2011 10 Cambridge Polymer Group

State-of-the-art – free radical suppression • Issue: Free-radicals persist or an induced in vivo – Require a method for removing free radicals • Solution 1: remove free radicals – Melt or anneal the material – Does not help in vivo • Solution 2: absorb free radicals – Free radical scavenger – antioxidant – D,L- α -tocopherol (Vitamin E) • Crosslink then dope • Blend then crosslink 4/19/2011 11 Cambridge Polymer Group

Vitamin E free radical removal CH 3 H O CH 3 CH 3 CH 3 CH 3 CH 3 O H 3 C α -tocopherol (Vitamin E, α -T, T-OH) CH 3 R + O 2 ROO ROOH + TO ROO + T-OH R + Vitamin-E 4/19/2011 12 Cambridge Polymer Group

Evolution in properties • Charnley – Biocompatible – 10-15 year life when implanted corrected • First generation (crosslinked) – Improved wear – Oxidation issues • Second generation (annealed and/or melted) – Removal of crosslinking free radicals – Sterilization and in vivo radicals remain • Third generation (free radical suppression) – Vitamin E doping – Improved fatigue strength 4/19/2011 13 Cambridge Polymer Group

Fatigue Crack Propagation 4/19/2011 14 Cambridge Polymer Group

Next generation • Virgin polyethylene – crack resistant, poor wear, oxidizes • Crosslinking – Improves wear but sacrifices toughness 2 wt% Inhomogeneous • Hybrid structure doping 0.02 wt% 0.05 wt% – Surface crosslinked - Low VE 100 kGy – Bulk tough - High VE – Antioxidant for protection Spatial 0.25 crosslinking 0.20 Vitamin E Index 0.15 0.10 Homogenize No homogenization 0.05 Homogenization for 16 hours 0.00 0 2 4 6 8 10 Depth (mm) 4/19/2011 15 Cambridge Polymer Group

Pin-on-disc wear testing 0.5 wt% (3) 1.2 Wear (2) surfaces (3) (3) (2) (2) (1) (1) (1) 1 0.05 wt% Fatigue resistance (MPa m1/2) 0.8 0.6 0.4 0.2 0 Highly cross-linked Low cross-linked bulk 100-kGy irradiated 100-kGy irradiated and surface melted 4/19/2011 16 GRADIENT Cambridge Polymer Group

The success • Total hip replacement has evolved – 1950s simple mechanical replacement – Materials incrementally improved – Highly successful • 20+ year implant life • >193,000 implants per year in US – Technology transferred • Knee • Shoulder • Small joints • Ankle • Spine Image: Ratner et al. 4/19/2011 17 Cambridge Polymer Group

Addressing Spine pain • In 2004 38 million Americans suffered from back pain – Muscle – Nerves – Bone – Joint failure • Most patients treated conservatively – anti-inflammatories and physical therapy • Degradation of the vertebral column more serious – Radiculopathy, localized pain and impingement • Annual cost for spine conditions $194 billion – Disc disorders $2.6 billion – Lost activity accounts for 176 million days and 80-90% suffer at some point • Treatment of the spine at same point as hip in 1960s – Gold standard is fusion 4/19/2011 18 Cambridge Polymer Group Image: http://www.holistix-treatments.co.uk

The human spine • Much more complex than hip joint • Supports the upper body – In activity loads can be 3x body weight and up • Protects the spinal chord – Provides a boney tunnel through which the spinal chord runs • Flexible – Allows rotation/flexion/extension – Hybrid structure of disc and vertebrae 4/19/2011 19 Cambridge Polymer Group Images: http://www.backpain-guide.com http://www.eorthopod.com

Spine biomechanics • The Intervertebral Disc (IVD) is a unique joint – Poorly vascularized and immune privileged – Complex structure • ply-like periphery (Annulus Fibrosus) • surrounds a jelly-like core (Nucleus Pulposus) • Hybrid structure – Annulus confines and contains nucleus – Nucleus transfers compressive loads to tensile loads in annulus – Annulus is not intended for purely compressive loads – Analogous to a bias (cross-ply) tire 4/19/2011 20 Cambridge Polymer Group Image: Bogduk

What can go wrong • The degenerative cascade – The IVD starts deteriorating from youth – IVD gradually dehydrates • Joint becomes lax • Annulus becomes damaged • Reduce disc height • Facet joints abnormally loaded • Pain – Biomechanics change • Bone remodelling • Osteophyte formation • Arthrosis – Deterioration also influenced by • Lifestyle, trauma, genetics, surgery… 4/19/2011 21 Cambridge Polymer Group Images: www.spineuniverse.com

Motion Preservation • Removal of nucleus – Height loss, Ligaments slacken – Abnormal loading • 700,000 annually • Relieves pressure on spinal chord • Removes material – loss of height Nucleus removal Fusion • 50-60% early success, 20-30% later relapse • Fusion – No motion ,Motion/load transferred • 300,000 annually • Prevents motion • 70% clinical success • Solution: Total disc replacement – Analogous to hip replacement – Engineering bearing – Polyethylene on metal 4/19/2011 22 Cambridge Polymer Group

Bioengineering approach • Fusion and total disc relieve symptoms by removal of pain sites – Changes load distribution in spinal column • Nucleus removal relieves symptoms by removing pressure – Collapses joint • Compromised biomechanics – Accelerates degradation Nucleus replacement • Need method that is – Less invasive • (easier surgery and shorter recovery times) – Preserves surrounding biomechanics • (keep functional structures) – Restores function • (device is biomechanically relevant) – Revisable • (should something go wrong) 4/19/2011 23 Cambridge Polymer Group

Initial attempts • First attempts implanted solid objects into disc space – Loaded endplates (subsidence) – Large incision • Replaced solid objects with expanding devices – Uneven endplate loading – No load sharing – Moderately large incision 4/19/2011 24 Cambridge Polymer Group