WS2024 Lecture 4: Resorbable Biomedical Polymers (II) & Permanent Biomedical Polymers (I) PDF

Lecture plan Dates Topic Lecture 15.10.2024 Fundamentals Biomedical Materials. Selection criteria for biomaterials for medical devices del Campo Physicochemical properties of polymer materials of relevance for biomedical applications, 22.10.2024...

Lecture plan Dates Topic Lecture 15.10.2024 Fundamentals Biomedical Materials. Selection criteria for biomaterials for medical devices del Campo Physicochemical properties of polymer materials of relevance for biomedical applications, 22.10.2024 Müller, Asensio and methods to characterize them 29.10.2024 Synthetic biomedical polymers, resorbable (I) del Campo 05.11.2024 Synthetic biomedical polymers, resorbable (II) and permanent (I) del Campo 12.11.2024 Synthetic biomedical polymers, permanent (II) del Campo 19.11.2024 Biomedical hydrogels Asensio 26.11.2024 Additive Manufacture of biomedical polymers Steudter 03.12.2024 Protein adsorption on surfaces. Non-fouling and non-thrombogenic polymers Sankaran 10.12.2024 Immune response to biomaterials Trujillo 17.12.2024 Smart Textiles, Intelligent Implants, Wearable devices and biosensors Sankaran 07.01.2025 Case studies: medical devices del Campo 14.01.2025 Case studies: medical devices del Campo 28.01.2025 EXAM (multiple choice text) 04.02.2025 Presentations students del Campo, Asensio 11.02.2025 Presentations students del Campo, Asensio 18.02.2025 Presentations students del Campo, Asensio www.leibniz-inm.de 1  Biomedical polymers Aránzazu del Campo Lecture 4: Synthetic, resorbable biomedical polymers (II) Synthetic, permanent biomedical polymers (I) www.leibniz-inm.de 2 Hydrolytic degradation rates of biomedical polymers attending to chemistry of backbone Non degradable: Polyolefins (PE, PP) Halogenated polymers (PVC, PTFE) Silicones This lecture Polyethers Polyacrylates (PMMA) Aromatic poly(esters) (PET) Polyamides (Nylon) Last lecture and this lecture Using data from Ulery et al., J. Polym. Sci. Part B: Polymer Physics, 2011 3 Outline 01 Other resorbable polymers: PSG and PU (follow-up previous lecture) 02 Permanent biomedical polymers (I): polyolefines, halogenated polymers 03 Next lecture: Permanent biomedical polymers (II) www.leibniz-inm.de 4 General properties of aliphatic polyesters used in biomedical applications − Hydrophobic character − Can be prepared with designed routes, to have predictable properties and batch-to-batch uniformity − Degradable, resorbable − Tunable physicochemical properties (degradability, mechanical properties…) through monomer composition, copolymerization and blending Synthesis methods for producing biodegradable aliphatic polyesters. − Thermoplastic character >> easy processable as melts − Easy to sterilize − Low price www.leibniz-inm.de 5 https://doi.org/10.1002/marc.202400475 Degradable aliphatic polyesters Last lecture This lecture 6 Poly(glycerol sebacate) (PGS) PGS Monomer Glycerol and sebacic acid (from plant sources) Synthesis method Polycondensation + crosslinking Tg (°C) - 23°C Tm (°C) -10 - 10°C Degradation Months - 2 years Young’s Modulus 0.01 - 1.5 MPa Ultimate tensile strength 0.4 -0.7 MPa Elongation at break 1.2 - 3 times original length Polymer type Elastomer www.leibniz-inm.de https://doi.org/10.1002/pi.3165 7 Synthesis of PGS Two steps: Polycondensation and crosslinking www.leibniz-inm.de 8 Synthesis of PGS Two steps: Polycondensation and crosslinking Prepolymerization Crosslinking in N2 atmosphere in vacuum Evolution of the Degree of Esterification (DE) of PGS samples during polymerization at different temperatures. >> Fast initial esterification followed by slower rate after a few hours. This is due to the difference in reactivity of primary and secondary hydroxyl groups in glycerol. www.leibniz-inm.de DOI 10.1021/acs.biomac.5b00018 9 Properties of PGS Physical status as function of DE Physical status of PGS synthesized at different temperatures and times (i.e. with different DE): brittle opaque wax soft translucent wax Viscous transluscent liquid soft sticky elastomer nonsticky elastomers www.leibniz-inm.de DOI 10.1021/acs.biomac.5b00018 10 Properties of PGS Mechanical properties of PGS as function of DE Stress−strain curves of PGS specimens prepared at 13°C with 42, 48, 66, and 78 h total thermal treatment www.leibniz-inm.de DOI 10.1021/acs.biomac.5b00018 11 Properties of PGS Mechanical properties of PGS as function of DE Degradation of PGS samples as function of DE. Samples prepared with 48, 66, 78, and 90 h of total thermal treatment www.leibniz-inm.de DOI 10.1021/acs.biomac.5b00018 times at 130 °C. Degradation was quantified by mass loss in12PBS Poly(glycerol sebacate) (PGS) Thermal properties DSC curve for dry PGS (black line) and PGS–Bioglass composites with 5%, 10% and 15% Bioglass (other lines). Tm = 5°C Broad sigmoidal transition between − 30 and − 10 °C Tg = -23°C corresponds to the glass transition of the amorphous PGS Exothermic peak at − 20°C during cooling and endothermic peak between −10 and 10°C during heating indicate that PGS is a semicrystalline polymer at room temperature. Tc = -18°C PGS is a soft amorphous material (elastomer) at body temperature of 37 °C www.leibniz-inm.de https://doi.org/10.1002/pi.3165 13 Derivatization of Poly(glycerol sebacate) Poly(glycerol sebacate urethane) (PGSU) Hydralese (Secant Group) In development: PGSU-based ocular drug delivery microimplants, gastroretentive rings and injectables www.leibniz-inm.de 14 Derivatization of Poly(glycerol sebacate) PGSU fibers: Hydralese®, Secan Group www.leibniz-inm.de 15 16 Exercise 1 Specify the basic function/s of the following medical devices, and identify the 3 most relevant functional features and material properties to be taken into account in their design Composite dental crown Silicone contact lens Wound dressing Cardiovascular stent 17 Exercise 1 Which tissues are subjected to this type of mechanical stress in the body? Tension forces Compression Fatigue Circumferential stress Cyclic stress Torque Shear stress Friction, wear 18 Exercise 1 Give an example of a medical device (different to those mentioned in Exercise 1) that needs to fulfil the following functional requirement? - Resistance to: Tension forces Compression forces Fatigue Circumferential stress Cyclic stress Torque Shear stress Friction, wear - Transparency - Lubricity - Degradability - Water absorption - Conductivity 19 Poly(urethanes) find versatile applications Poly(urethanes) History 1937: PUs were synthesized by Professor Otto Bayer 1958: PU was used as coating for breast prostheses 1970-80s: blood contacting material of choice in cardiovascular devices (intended to be non degradable, Biomer®) 1980s: applied in long-term implants lead to failures of pacemaker leads and breast implant coatings. Retracted from market 1990s - : following intensive research in biodegradation mechanisms, PUs with enhanced biostability for in vivo long-term applications and new classes of bioresorbable materials Prof. Otto Bayer demonstrates PU foam, 1952 21 Poly(urethanes) (PUs) General properties − Tough − Biocompatible − Hemocompatible − Can be formulated as thermoplastic elastomers (TPUs) or as thermosets. − Easy adjustable mechanics by tuning composition − Degradability adjustable by tuning composition − Processable using extrusion, injection molding, film blowing, solution dipping, and two-part liquid molding. − Expensive! www.leibniz-inm.de 22 Thermoplastic polyester-urethanes (TPEUs) and thermoplastic polyester-urethane-ureas (TPEUU) Synthesis Synthesized by polyaddition of macrodiols with diisocyanates and chain extenders (diols and diamines) Urethane linkages are formed by the reaction of isocyanates with hydroxyl-functional molecules, and urea linkages are formed by reaction with amines. Urethane Urea www.leibniz-inm.de 23 Classes of PUs Thermoplastic and Thermosets All PU structures can be divided into two principal families which are (i) Thermosets (ii) Thermoplastic PUs (TPUs). www.leibniz-inm.de https://doi.org/10.1016/j.bioactmat.2020.10.002 24 Classes of PUs Thermoplastic and Thermosets PU structures can be divided into two principal families: (i) thermosets and (ii) thermoplastic polyurethanes (TPUs). Thermoplastic PUs consist of LINEAR and UNCROSSLINKED structures synthesized from polydiols and diisocyanates. They are mostly obtained by a two-steps process: (i) The synthesis of a PREPOLYMER with –NCO ending chains by reaction of a polydiol (typically with polyester or polyether backbone) with an excess of diisocyanate (at least 2:1 NCO:OH molar ratio). (ii) Reaction of a chain extender (typically a short diol as the 1,4 Butanediol (BDO)) with the prepolymer. This procedure allows a fine control on the final linear structure. Thermoset PUs are prepared by mixing polyols and polyisocyanates with at least one of the monomers with functionality >4 in a one pot process, which leads to CHEMICALLY CROSSLINKED 3D NETWORKS. In many cases, thermoset PUs are used as foams and their formulation include a surfactant and a blowing agent. In opposition to TPUs, the chemically crosslinked organization make it unable for these materials to be thermo-reprocessed or soluble. www.leibniz-inm.de 25 Thermoplastic PUs Soft and hard segments in TPUs, several phases from micro-segregations can be observed between the so- called hard segment (HS), usually based on rigid diisocyanate and the chain extender, and the soft segment (SS) which is mainly based on a flexible and long diol. This segregation into organized domains is due to physical interactions between PU chains in the form of hydrogen-bonding between urethane functions. www.leibniz-inm.de 26 Thermoplastic PUs Soft and hard segments www.leibniz-inm.de 27 Thermoplastic PUs Soft and hard segments The soft segment typically has a glass transition temperature below RT and is therefore rubbery and amorphous at application temperature. In the hard segments, hydrogen bonding between urethane and urea groups of adjacent polymer chains induces the formation of ordered hard domains, which function as physical cross-links that resist flow when stress is applied to the material → elastomeric behaviour. To process the polymer, the physical cross-links are disrupted by heating the material above the hard segment melting transition. The relative fractions of the hard and soft segments affect the mechanical properties of segmented PUs. www.leibniz-inm.de 28 Synthesis of TPUs Synthesis typically stars by preparing a PREPOLYMER by reacting a polyol with an excess of diisocyanate to form NCO-terminated prepolymers. To increase the reaction rate, urethane catalysts (such as tertiary amines) and/or elevated temperatures (60–90°C) may be used. Depending on the NCO:OH ratio, prepolymer intermediates with targeted properties can be easily prepared. To prepare high molecular-weight polymers, prepolymers are chain extended by adding a short-chain (e.g.,