Biocompatible Materials: Polymers in Medicine (HS2024) PDF

376-1714-00L Biocompatible Materials ▪ Polymers in use for medicine 18.12.2024 Prof. Dr. Katharina Maniura, Empa, Biointerfaces/ D-HEST Dr. Markus Rottmar, Empa, Biointerfaces Prof. Dr. Marcy Zenobi-Wong, ETHZ, D-HEST, Tissue Engineering & Fabrication December 18, 2024...

376-1714-00L Biocompatible Materials ▪ Polymers in use for medicine 18.12.2024 Prof. Dr. Katharina Maniura, Empa, Biointerfaces/ D-HEST Dr. Markus Rottmar, Empa, Biointerfaces Prof. Dr. Marcy Zenobi-Wong, ETHZ, D-HEST, Tissue Engineering & Fabrication December 18, 2024 Katharina Maniura Teaching goals Repetition: - Different generation biomaterials - What are polymers? - Properties Degradable polymers for medical use Properties Types Applications for degradable polymers Structural polymers for medical use Applications for structural polymers Properties December 18, 2024 Katharina Maniura 2 Biomaterials Biomaterials of the 1st generation prostheses that are in tight contact with the body but are easily removable, e.g. dental prosthesis, artificial eye, etc. Biomaterials of the 2nd generation man-made devices that take over a specific, natural, remain in the body and are not degradable, e.g. hip implants, artificial heart, etc. Biomaterials of the 3rd generation designed to stimulate specific cellular responses at the molecular level and to combine the concepts of bioactive and resorbable materials they are supposed to help the body heal itself by prompting cells to repair their own tissues. December 18, 2024 Katharina Maniura 3 Polymers for use in medicine should be: December 18, 2024 Katharina Maniura 4 What kind of applications? synthetic polymers degradable non-degradable 50 m December 18, 2024 Katharina Maniura 5 Resorbability? * note: PU is a synthetic polymer, but can undergo hydrolysis December 18, 2024 Katharina Maniura 6 Polymers , PLA, PGA,…. December 18, 2024 Katharina Maniura 7 Polymers – repetition (poly = many, meros = particle) Monomer → Dimer →Trimer →→→ Oligomer →→→ Polymer ▪ ▪ ▪ ▪ December 18, 2024 Katharina Maniura 8 Polymers – constitution December 18, 2024 Katharina Maniura 9 Polymers – configuration December 18, 2024 Katharina Maniura 10 December 18, 2024 Katharina Maniura 11  g m December 18, 2024 Katharina Maniura 12  below Tg polymers are hard and brittle above Tg polymers are soft and flexible like rubber due to some mobility physical and mechanical properties of polymers change December 18, 2024 Katharina Maniura 13  Big bulky pendant groups can lower the Tg. They limit how closely the polymer chains can pack together. The further they are from each other, the more easily they can move around. This lowers the Tg, in the same way a plasticizer does. There is more free volume in the polymer. The more free volume, the lower the Tg generally. https://www.pslc.ws/mactest/tg.htm December 18, 2024 Katharina Maniura 14 Handout December 18, 2024 Katharina Maniura 15 Polymers – mechanical properties December 18, 2024 Katharina Maniura 16 Polymers – mechanical/ thermal properties – success or failure December 18, 2024 Katharina Maniura 17 December 18, 2024 Katharina Maniura 18 December 18, 2024 Katharina Maniura 19 Synthesis of polymers Chain polymerization Radical polymerization Step polymerization Ionic polymerization Polycondensation Ring-opening polymerization Transesterification/-amidation Slow/controlled monomer conversion Initiated step-by-step One initiation step Fast monomer conversion Fast MW-increase Slow MW-increase December 18, 2024 Katharina Maniura 20 Structure-morphology-property relationship December 18, 2024 Katharina Maniura 21 Common polymers in medicine I December 18, 2024 Katharina Maniura 22 Common polymers in medicine II December 18, 2024 Katharina Maniura 23 Common polymers in medicine III December 18, 2024 Katharina Maniura 24 Common polymers in medicine IV December 18, 2024 Katharina Maniura 25 Degradation Mechanisms ▪ Enzymatic degradation ▪ Hydrolysis (depends on main chain structure) Homogenous degradation Heterogenous degradation: random pieces to small molecules over time December 18, 2024 Katharina Maniura 26 December 18, 2024 Katharina Maniura 27 December 18, 2024 Katharina Maniura 28  Degradation rate determined by chemistry > PGA ? December 18, 2024 Katharina Maniura 29 Degradable polymers – an overview December 18, 2024 Katharina Maniura 30  ▪ ▪ ▪ December 18, 2024 Katharina Maniura 31 December 18, 2024 Katharina Maniura 32 December 18, 2024 Katharina Maniura 33 December 18, 2024 Katharina Maniura 34  autocatalytic degradation in material (bulk erosion) hydrolytic degradation and enzymatic degradation (esterase) increased chance of inflammation upon degradation irritation during healing process December 18, 2024 Katharina Maniura 35 December 18, 2024 Katharina Maniura 36 December 18, 2024 Katharina Maniura 37 December 18, 2024 Katharina Maniura 38 December 18, 2024 Katharina Maniura 39 December 18, 2024 Katharina Maniura 40 December 18, 2024 Katharina Maniura 41 Factors that influence polymer degradation behavior ▪ Chemical Structure and Chemical Composition ▪ Distribution of Repeat Units in Multimers ▪ Molecular Weight ▪ Polydispersity ▪ Presence of Low Mw Compounds (monomer, oligomers, solvents, plasticizers, etc) ▪ Presence of Ionic Groups ▪ Presence of Chain Defects ▪ Presence of Unexpected Units ▪ Configurational Structure ▪ Morphology (crystallinity, presence of microstructure, orientation and residue stress) ▪ Processing methods & Conditions ▪ Method of Sterilization ▪ Annealing ▪ Storage History ▪ Site of Implantation ▪ Absorbed Compounds ▪ Physiochemical Factors (shape, size) ▪ Mechanism of Hydrolysis (enzymes vs water) December 18, 2024 Katharina Maniura 42 Medical use for structural polymers Hüftgelenk December 18, 2024 Katharina Maniura 43 Overview structural polymers ▪ Plastics in medical technology products (2012): 5.5 Mio. t HT–Plastics LCP price, properties range of use: 160 oC-260 oC price: > 15 $/kg PPS Engineering Plastics amounts PBT PET range of use: < 140 oC price: 5 to 10 $/kg PA POM PMMA Standard Plastics range of use: < 90 oC PVC PP (UH-MW-)PE price: < 2 $/kg November 16, 2012 Katharina Maniura December 06, 2023 Katharina Maniura 44 44 Structural polymers – medical use Type Polymer Application PE poly(ethylene) hip prostheses, orthopedic implants and ortheses PP poly(propylene) syringes, prostheses, blister packaging PET, PBT polyester nonwoven media for blood filtration and solids separations PVC poly(vinylchloride) bags for blood and drug solutions, gloves, tubings, blister PA 12 polyamide tubing, catheter PU polyurethane artificial hearts, catheters PC polycarbonate dialysis, cardiac surgery, surgical instruments PEEK polyetheretherketone dental and surgery instruments, parts of endoscops/dialysis PPS poly(phenylene sulfide) nonwoven structures for filtration (repeated sterilisation) COC cyclic olefine copolymer packaging (blister), vials and syringes, microtiter plates LCP liquid crystaline polymer metal replace in medical equipment and surgical instruments PMMA poly(methyl methacrylate) fracture fixation, intraocular lenses, bone cement PHEMA poly(hydroxyethyl methacrylate) contact lenses PTFE poly(tetrafluoroethylene) prostheses, catheters, sutures PDMS poly(dimethylsiloxane) breast, penile and testicular prostheses ▪ do not contain water soluble bonds under physiological conditions at 37 oC ▪ remain stable very long without dissolution in water ▪ can provide shape to for medical implants December 18, 2024 Katharina Maniura 45  Polyethylene - PE H H radical chain n C C reaction ~ CH2 CH ~ H H H n ethylene polyethylene (PE) Polyethylene is classified into several different categories varying density, branching and molecular weight. - LDPE: UHMWPE ultra high molecular weight polyethylene ULMWPE (PE-wax) ultra low molecular weight polyethylene HMWPE high molecular weight polyethylene - LLDPE: HDPE high density polyethylene HDXLPE high density cross-linked polyethylene PEX cross-linked polyethylene MDPE medium density polyethylene - HDPE: LDPE low density polyethylene LLDPE linear low density polyethylene VLDPE very low density polyethylene - PE(X): December 18, 2024 Katharina Maniura 46 Polyethylene - PE December 18, 2024 Katharina Maniura 47 UHMWPE – research December 18, 2024 Katharina Maniura 48 Research to market I https://www.mathysmedical.com December 18, 2024 Katharina Maniura Research to market II https://www.mathysmedical.com December 18, 2024 Katharina Maniura UHMWPE - Dyneema Purity® ▪ Fibrous material: due to HMW extremely difficult to process ▪ Strong fibres - strength-to-weight ratio: 10-100x higher than steel ▪ Low coefficient of abrasion (wear) ▪ Applications as: ▪ Sutures ▪ Delivery system for VCF (vertebral compression fracture) ▪ Alternative to ACL-fixation (anterior cruciate ligament) ▪ Cardiovascular applications December 18, 2024 Katharina Maniura 51 UHMWPE - Dyneema Purity® https://www.youtube.com/watch?v=spdyIKro-nk and others... December 18, 2024 Katharina Maniura 52 PTFE – poly(tetrafluoroethylene) ▪ A synthetic fluoropolymer which finds numerous applications. ▪ PTFE's most well-known trademark in the industry is the DuPont brand name Teflon or GoreTex 1 F H F H free radical ~ CH CF2 CF22~ CH n C C High pressure H F H F n tetrafluoroethylene PTFE 2 Fluorination of polyethylene December 18, 2024 Katharina Maniura 53 PTFE – poly(tetrafluoroethylene) ▪ high density: 2.2 g/cm³ ▪ Tm = 327 oC; degradation above 260 oC ▪ PTFE's coefficient of friction is 0.1 or less, which is very low ▪ excellent dielectric properties, therefore insulator in cables, etc. ▪ often used as a high-performance substitute for polyethylene (price !) ▪ exhibits creep (= deformation at constant load) → can be positive and negative depending on the application ▪ chemically inert ▪ extremely hydrophobic -> blood compatibility Contact angle of water on Teflon surface December 14, 18, 2022 2024 Katharina Maniura 54 PTFE – examples: Gore Medical Abdominal wall reconstruction Cardiac patches & membranes Lung disease Obesity Cardiovascular diseases For more info: www.goremedical.com December 18, 2024 Katharina Maniura 55 Polycarbonates Polycarbonate: CH3 O CH3 O HO C OH + Cl-C-Cl -O C O-C- n CH CH 3 3 A-A: bisphenol B-B: phosgene Polycarbonate (PC) ▪ Interesting features: temperature resistance, impact resistance and optical properties position them between commody plastics and engineering plastics ▪ similar to PMMA but polycarbonate is stronger and more expensive ▪ highly transparent to visible light and has very good light transmission ▪ CR-39 is a specific polycarbonate material with good optical and mechanical properties, frequently used for eyeglass lenses December 18, 2024 Katharina Maniura 56 Polyurethanes December 18, 2024 Katharina Maniura 57 Other polymers - handout CH3 ▪ Poly(methylmethacrylate) (PMMA) C H~ Bone cement, fracture fixation, ~ CH2 H C=On intraocular lenses O CH 3 CH3 ▪ Poly(hydroxyethylmethacrylate) (PHEMA) ~ CH2 C H~ Contact lenses C=On H O C2H5 HO ▪ Poly(vinylchloride) (PVC) ~ CH2 CH ~ Bags for blood and drug solutions, H Cl n gloves, tubings, blister ▪ Poly(propylene) (PP) ~ CH2 CH ~ syringes, prostheses, blister packaging H n CH 3 December 18, 2024 Katharina Maniura 58 PMMA - applications December 18, 2024 Katharina Maniura 59 Summary: Synthetic polymers ▪ Degradable polymers ▪ hydrolytic degradation ▪ implants, degradation time tunable ▪ degradation (time) affects mechanical properties ▪ Structural polymers ▪ shape giving ▪ long lasting ▪ not degradable by hydrolysis under native conditions ▪ need to be removed when implant is not used any longer December 18, 2024 Katharina Maniura 60 Outlook: polymeric biomaterials -> nanotechnology ▪ „designer“ materials ▪ 3D structures more defined → novel types of processing ▪ Enzymatically degradable by cellular demand/response ▪ Intelligent materials that can respond to their environment ▪ pH ▪ Concentration gradients ▪ Temperature ▪ Oxygen December 18, 2024 Katharina Maniura 61