WS2024 Lecture 3: Degradable Biomedical Polymers Handout 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) del Campo 12.11.2024 Synthetic biomedical polymers, non-resorbable (I) 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 3: Synthetic, resorbable biomedical polymers www.leibniz-inm.de 2 Outline 01 Degradation and clearance mechanisms of biomedical polymers 02 Resorbable aliphatic polyesters 03 Other resorbable polymers (next lecture) www.leibniz-inm.de 3 Classification of Polymeric Biomaterials attending to durability: Resorbable Durable PLGA Nylon VICRYL, J&J ETHILON, J&J Vicryl sutur 6-0, V-18 needle, 70 cm purple filament Ethilon suture 2-0, FS needle, 45 cm blue Tensile strength: filament 2 weeks - 75% ETHILON Suture is a nonabsorbable, sterile 3 weeks - 50% surgical monofilament suture composed of the 4 weeks - 25% long-chain aliphatic polymers Nylon 6 and The vicryl suture is completely absorbed within 56 - 70 days. Nylon 6,6. 4 Example Resorbable Biomedical Polymer Poly(D,L-lactide-co-glycolide) = PLGA (Resomer®) http://www.klsmartinnorthamerica.com/products/implants/max illofacial/sonicweld-rxR/implant-selection/  Resorbable material Definition Resorption: The breakdown of a structure and consequent assimilation of resulting components into their environment Breakdown: typically degradation (hydrolytic, enzymatic, oxidative), but also dissolution Assimilation: clearance by the body, either metabolic processing or excretion Definitions of Biomaterials for the Twenty-First Century, Proceedings of a Consensus Conference 2018 6  Degradation Hydrolytic degradation of a polymer consists of the scission of water-labile bonds (i.e. glycosides, carbonates, esters or amides) of its backbone by the influence of water molecules. Enzymatic degradation involves the intervention of enzymes. Oxidative degradation involves the deterioration of polymers by the mechanism of oxidation in presence of atmospheric oxygen or oxidants in the biological environment. As degradation occurs, the molecular weight of the polymer chains decreases. www.leibniz-inm.de Resorbable biomedical polymers Factors influencing degradation rate Material parameters: ‒ Chemistry of the polymer backbone (types of bonds) ‒ Molar mass ‒ Hydrophobicity/hydrophilicity ‒ Crystallinity ‒ Water adsorption, water diffusion ‒ Degradation products solubility and diffusion Device and external conditions: ‒ Device size and geometry ‒ pH, temperature, tissue type (body part), pathology …. ‒ Degradation mechanism might also change depending on environmental conditions Brannigan and Dove, Biomater. Sci., 2017, 5, 9 8 Factors influencing the degradation of bioresorbable devices www.leibniz-inm.de https://link.springer.com/chapter/10.1007/978-3-319-89542-0_13 9 ester bond PLLA). Although this diffusion coefficient may affect the macroscopic degradation of a material, degradation kinetics Degradation mechanisms are still determined by the hydrolysis reaction on a molecular scale. In simplistic terms, hydrolytic degradation of synthetic materials can be split into two modes; bulk degradation and surface erosion (Fig. 2), however, both mechanisms are not necessarily independent of each other.22,23 ‒ Surface erosion: rate of polymer degradation and mass relief at the water-biomaterial interface is greater than rate of water diffusion into the bulk of the material, leading to a biomaterial that degrades almost entirely at its surface. ‒ Bulk erosion: water diffusion in the biomaterials is much faster than degradation Fig. 2 Degradation mechanisms; surface erosion versus bulk at the biomaterials surface, leading to ds. degradation. degradation and subsequent mass loss occurring throughout the bulk of the material. This journal is © The Royal Society of Chemistry 2017 Brannigan and Dove, Biomater. Sci., 2017, 5, 9 10 Hydrolytically degradable polymers Polymers that possess hydrolytically labile chemical bonds in their backbone and can be broken down in an aqueous environment (the body) Hydrolytic degradation of a polymer consists of the scission of water-labile bonds (i.e. glycosides, carbonates, esters or amides) of its backbone by the influence of water molecules. Hydrolytic cleavage mechanism of acetals, esters, amides, and degradation products 11 Hydrolytic degradation rates of biomedical polymers attending to chemistry of backbone Using data from Ulery et al., J. Polym. Sci. Part B: Polymer Physics, 2011 12 Degradation rates of biomedical polymers www.leibniz-inm.de Ulery et al., J. Polym. Sci. Part B: Polymer Physics, 2011 13 Clearance of biomedical polymers by the body Biodegradable polymers undergo cleavage of bonds in the polymeric backbone producing small molecules that can be absorbed in the biochemical pathways of the body. Example: Poly(L-glutamic acid) and poly(aspartic acid) are highly susceptible to degradation by lysosomal enzymes, producing monomeric amino acids as degradation products Semi-degradable polymer backbones composed by non-degradable polymer blocks with degradable linkers. Polymer backbones that are not degradable enter the bloodstream and are eliminated at the liver or at the kidney, provided they are below a certain size (for the kidney). In general, the rate of renal elimination is inversely correlated with the MW of the polymers. For example, the molecular weight thresholds for PEG is about 30 kDa. The metabolism of the polymer and its elimination from the body, are two very important features in biomedical polymer design. www.leibniz-inm.de Outline 01 Degradation and clearance mechanisms of biomedical polymers 02 Resorbable aliphatic polyesters 03 Other resorbable polymers (next lecture) www.leibniz-inm.de 15 Aliphatic polyesters are widely used, degradable biomedical polymers 16 Degradable aliphatic polyesters Degradation mechanisms Only polyesters with reasonably short aliphatic chains show degradation rates fast enough to be utilized as degradable polymers for biomedical applications The main process during degradation of aliphatic polyesters includes: Diffusion of water into the amorphous regions of the polymer Hydrolysis of ester bonds at the amorphous regions (autocatalytic process) The penetration of water into aliphatic polyesters is much faster than the hydrolysis rate of the ester bonds. Therefore the degradation of aliphatic polyesters is typically a bulk degradation process. The degradation proceeds either at the surface or in the bulk and is controlled by a wide variety of compositional and property variables chemical composition (spacer length, substituents), stereochemical structure, monomer sequence (in copolymers), molecular weight and distribution, the presence of residual monomers, oligomers and other low molecular weight products, size and shape of the specimen) and the degradation environment, e.g., presence of moisture, oxygen, microorganisms, enzymes, pH, temperature, etc. Natural lipases can enzymatically degrade aliphatic polyesters, but struggle to hydrolyze polyesters with an optically active carbon such as PHB and PLLA (poly-L-lactide) Degradation of polyesters generates a FREE ACID in the biological milieu >> local change in pH 17 How do the polymer mass and the molecular weight change during surface erosion or bulk degradation? www.leibniz-inm.de 18  constant and is relatively independent of morphology or type i.e. amorphous poly(D,L-lactic acid-co-L-lactic acid) (PDLLA-co- Scheme 1 Simplified example of cleavage of hydrolysable ester bond PLLA). Although this diffusion coefficient may affect the and products. How do the polymer mass and the molecular weight macroscopic degradation of a material, degradation kinetics are still determined by the hydrolysis reaction on a molecular change during surface erosion or bulk degradation? scale. In simplistic terms, hydrolytic degradation of synthetic materials can be split into two modes; bulk degradation and surface erosion (Fig. 2), however, both mechanisms are not necessarily independent of each other.22,23 Fig. 2 Degradation mechanisms; surface erosion versus bulk Scheme 2 Example conjugate structures of hydrolysable bonds. degradation. 10 | Biomater. Sci., 2017, 5, 9–21 This journal is © The Royal Society of Chemistry 2017 www.leibniz-inm.de https://link.springer.com/chapter/10.1007/978-3-319-89542-0_13 19 SYNTHESIS of aliphatic polyesters Methods − Polycondensation of hydroxyacids, or diols with diacids/diesters − Ring-opening polymerization (ROP) of lactones − Bacterial synthesis www.leibniz-inm.de 20 Ring opening polymerization of lactones www.leibniz-inm.de 21 Ring opening polymerization of lactones − Monomers are lactones of different ring-sizes, sometimes with substituents − Polymer with high molecular weight can be achieved − Living/controlled polymerization mechanism leads to polymers of narrow molecular weight distribution with a molecular weight determined by the monomer-to-initiator molar ratio − Polymerization needs an initiator/catalyst − In most cases, a coordination-insertion initiator/catalyst system is used www.leibniz-inm.de 22 Coordination-insertion ROP Organometallic (metal alkoxides) are typical initiators, e.g. Sn(Oct)2. The initiator coordinates to the carbonyl of the monomer, followed by cleavage of the acyl-oxygen bond of the monomer and simultaneous insertion of the monomer into the metal alkoxide bond. Sn(Oct)2 = Organometallic acts as an initiator in the “coordination-insertion“ mechanism Organometallic acts as a catalyst in the presence of nucleophiles (Nu) C. Jérôme, P. Lecomte, Adv. Drug Delivery Rev. 2008, 60, 1056 - 1076 www.leibniz-inm.de 23 Polyglycolide (PGA) Monomer Glycolide (from glycolic acid, from sugar fermentation) Molar mass (kDa) > 100 kDa Tg (°C) 36 Tm (°C) 223 Crystallinity (%) 45-55 Degradation 1-6 months Modulus 7 – 8.4 GPa Strength ~900 MPa for oriented fibre Elongation at break (%) 30 Polymer type Thermoplastic www.leibniz-inm.de Roi et al., Progress in Polym. Sci., 2012; Manavitehrani et al., Polymers 2016, 8, 20 Polyglycolide (PGA) PGA is a semicrystalline polymer: the PGA chains with planar zig-zag conformation arrange to form crystals within an amorphous PGA matrix. The crystalline regions have higher density (1.69 g/cm3) and lower degradation rate than the amorphous regions. By tuning the crystallinity during processing, the degradation rate can be tuned Crystal structure of PGA www.leibniz-inm.de Roi et al., Progress in Polym. Sci., 2012; Manavitehrani et al., Polymers 2016, 8, 20 Polyglycolide (PGA) PGA biomedical devices: Degradable suture DEXON® in the market since 1970 Internal bone pin Biofix® from 1984 to 1996 Since 1996, Biofix was made of poly(L-lactide) (PLLA) for better long- term stability Scaffolds for tissue engineering Limitation: Rapid degradation leads to loss of mechanical strength and significant local production of glycolic acid. While glycolic acid is bioresorbable by cells via the citric acid cycle, high level of glycolic acid have been linked to a strong, undesired inflammatory response www.leibniz-inm.de Roi et al., Progress in Polym. Sci., 2012; Manavitehrani et al., Polymers 2016, 8, 20 PGA medical device GEM NEUROTUBE, Synovis The NEUROTUBE device replaces the classic nerve graft technique for the repair of nerve gaps. The NEUROTUBE device is an absorbable woven Polyglycolic Acid (PGA) mesh nerve conduit used to facilitate the healing of peripheral nerve injury. It is also designed to encourage axonal growth across gaps, uniting disrupted peripheral nerve bundles. www.leibniz-inm.de https://quamedical.nl/documenten/synovis/Neurotube_Product_Sheet.pdf 27 Polylactide (PLA) PLLA PDLLA Monomer L-lactide (bacterial L-lactide + D-lactide fermentation of starch/sugar - biobased) Synthesis method ROP ROP Molar mass (kDa) > 100 > 100 Tg (°C) 50-65 50-60 Tm (°C) 170-190 amorphous Crystallinity (%) 37 % 0 Degradation > 4 years 1 year Modulus 3.5 GPa 2 GPa Strength 80 MPa 35 MPa Elongation at break (%) 30 - 40 5 - 10 Polymer type Thermoplastic Thermoplastic www.leibniz-inm.de Roi et al., Progress in Polym. Sci., 2012 Polylactide (PLA) Lactic acid dimerizes to form the cyclic form lactide (bis-lactone) with heat and humid atmosphere, which is then polymerized: Polymerization of lactic acid can be conducted by: ‒ Polycondensation of lactic acid yields low molecular-weight PLA (degree of polymerization (DP) is normally less than 100) ‒ ROP of lactide yields higher molecular weight polymers: Natureworks (Dow&Cargill), GMP-grade PLA and PLGA: Purasorb (Purac), Lactel (Birmingham Polymers), Reso-mer (Boehringer Ingelheim) and Medisorb (Alkermes) www.leibniz-inm.de Polylactide (PLA) PLA is available in four forms: poly(L-lactide) (PLLA), poly(D-lactide) (PDLA), poly(D,L-lactide) (PDLLA) and meso- poly(lactic acid). ‒ Only PLLA and PDLLA are significantly used as biomaterials High performance polymer: High mechanical strength and stiffness, versatile processing, and relatively low price Explosive market growth in packaging, textiles and other short-time commodity applications PLA MARKET GROWTH PLA Market size was Mill USD 0.5 Mt in 2015 (PE+PP Market size was 150 Mt in 2015) https://www.gminsights.com The methyl group in PLA causes the polymer to be more hydrophobic and stable against hydrolysis than PGA ‒ High molecular weight PLLA takes > 4 years to be completely resorbed in vivo www.leibniz-inm.de Poly(L-lactide-co-glycolide) (PLLGA) Random copolymer of PLLA and PGA Reported degradation rate of PLGA are faster than for pure PGA and PLLA, with the fastest degradation rate corresponding to PLGA 50:50, WHY? PGA and PLLA are semi-crystalline. As they are copolymerized, crystallinity decreases. The ”U-shape” trend in the degradation time of PLGAs can be related to the decrease in crystallinity with increasing comonomer content, which makes it easier for water to penetrate: www.leibniz-inm.de  Applications of bioresorbable implants for orthopedic applications (PLA and PGLA based) https://link.springer.com/chapter/10.1007/978-3-319-89542-0_13 www.leibniz-inm.de 32 Legend Company Product Composition Resorption A Depuy Synthes RAPIDSORB® Preshaped Orbital Floor Plate 85:15 PLGA 12 months B KLS Martin Group Resorb x® and Resorb xG Plates PDLLA, 85:15 PLLA/PGA 12–30 months C Stryker® Delta System Plates 85:5:10 PLLA/PDLA/PGA 8–13 months D Depuy Synthes RAPIDSORB® Contourable Mesh 85:15 PLGA 12 months E KLS Martin Resorb x® Alveolar Protector PDLLA 12–24 months F ACUTE Innovations® BioBridge® Resorbable Chest Wall Stabilization Plate 70:30 PLDLA 18–24 months G Smith & Nephew, Inc. TWINFIX® Ultra HA Suture Anchor PLLA/HA – H KLS Martin Group Resorb x® Membrane PDLLA 12–24 months I Arthrex BioComposite SwiveLock® Tenodesis 85:15 PLLA/β-TCP – J Depuy Synthes Biocryl Rapide® Suture Anchors 70:30 PLGA/β-TCP 24 months K Inion Inc. S-2 Biodegradable Anterior Thoraco-Lumbar Fusion System PLLA and PDLA 24–48 months L Arthrex BioComposite Distal Biceps Implant System 85:15 PLLA/β-TCP – M Abbott Absorb GT1 Vascular Stent PLLA/HA 36 months N Arthrex BioComposite Tenodesis Screw Master Set 85:15 PLLA/β-TCP – O Smith & Nephew, Inc. OSTEORAPTOR® Suture Anchors PLLA/HA – P Depuy Synthes Resorbable Sleeve for Screws Stabilizing Intramedullary Nails 70:30 PLDLA 18–24 months Q Arthrex Micro-Compression FT Screws PLLA – R Arthrex BioComposite Pushlock Suture Anchor for Patellofemoral Dysfunction 85:15 PLLA/β-TCP >24 months S Depuy Synthes MILAGRO® Advance Interference Screw 70:30 PLGA/β-TCP 24 months U Arthrex BioComposite SwiveLock® for Medial Patellofemoral Ligament Procedures 85:15 PLLA/β-TCP >24 months V Wright Medical RFS Pins and Solid/Cannulated Screws 85:15 PLGA 24 months W Medtronic Polysorb 2 mm Soft Tissue Anchor System 18:82 PGA/PLA 12–15 months X Arthrex BioComposite SwiveLock® for Achilles SpeedBridge® 85:15 PLLA/β-TCP >24 months Y Arthrex BioComposite Interference Screw 70:30 PLDLA/BCP >24 months Z Arthrex BioComposite SwiveLock® & BioComposite SutureTak Anchors 85:15 PLDLA/BCP >24 months www.leibniz-inm.de 33 https://link.springer.com/chapter/10.1007/978-3-319-89542-0_13 PLGA biomedical products Sutures Vicryl® (Ethicon) since 1974, a 10:90 PLGA braided thread Vicryl Rapide® degrades faster than Vicryl® since it is irradiated during production (lowers MW). Vicryl Plus Antibacterial® is impregnated with triclosan antibacterial agent. Polysorb® (Syneture) and Purasorb® (Purac Biomaterials) are also suture materials composed of PLGA. www.leibniz-inm.de 34 Biological and physiological pathways for the degradation of PLA, PGA and PLGA in vivo www.leibniz-inm.de https://link.springer.com/chapter/10.1007/978-3-319-89542-0_13 35 Polyhydroxyalkanoates (PHA) The only bioplastic completely synthesized by microorganisms Homopolymers, random copolymers, and block copolymers of PHAs can be produced depending on the bacterial species and growth conditions PHA inclusions (0.2 – 0.5 µm) can make up as much as 90% of dry cell weight www.leibniz-inm.de 36 Poly(3-hydroxybutyrate) (PHB) Synthesized roduced by fermentation, either in batch, fed batch or continuous cultures using improved bacterial strains, cultured on inexpensive carbon sources such as beet and cane molasses, corn starch, alcohols and vegetable oils, combined with multi-stage fermentation systems. Semi-crystalline isotactic polymer Tg 5 °C , Tm 160 – 180 °C. Easy processing Mechanical properties depend on molecular weight, crystallinity and orientation (processing conditions) Hydrolytic degradation of PHB results in the formation of D-(−)-3-hydroxybutyric acid, a normal blood constituent. Degradation product is less acidic than degradation products from PGLA www.leibniz-inm.de 37 Poly(4-hydroxybutyrate) (P4HB) GalaFLEXTM Scaffold for plastic and reconstructive surgery. It is designed to provide soft tissue reinforcement during healing phase after surgery www.leibniz-inm.de 38 Poly(hydroxyvalerate-co-3-hydroxybutyrate), PHBV PHB is copolymerized with 3-hydroxyvalerate to create PHBV PHBV is less crystalline than PHB. Tm 80 – 160 °C and Tg −5 to –20 °C depending on HV content. PHBV has been used in tissue engineering of bone, cartilage, tendon, skin, and nerves. To speed degradation rate of PHBV, copolymerization or blending of PHB or PHBV with PLLA, PDLLA, PLGA, poly(dioxanone), poly(caprolactone), or polyethers is used. www.leibniz-inm.de 39 Polycaprolactone (PCL) www.leibniz-inm.de 40 Polycaprolactone (PCL) Semicrystalline polyester with great organic solvent solubility Tm 55 – 60 °C, Tg −54 °C Low tensile strength (~23 MPa), but very high elongation at breakage (4700%). Good elastic biomaterial. Properties highly dependent on crystalline degree Very low in vivo degradation rate (2-3 years). Degradation rate depends on molecular weight and degree of crystallinity. Can be enzymatically degraded in the environment, but not in vivo. pCL is often blended or copolymerized with PLLA; PDLLA, PLGA and polyethers for faster degradation PCL can be processed as microspheres, electrospun fibers, or porous scaffolds by porogen leaching. Application as tissue engineering scaffolds for regeneration of bone, ligament, cartilage, skin, nerve, and vascular tissues. www.leibniz-inm.de 41 Study of enzymatic and oxidative degradation of PCL PCL and supramolecular PCL Materials: Semicrystalline PCL: PCL2000, PCL800 Supramolecular PCLs: PCL-BU (bis-urea): PCL2000-BU PCL-UPy (ureidopyrimidinone): PCL2000-UPy, PCL800-Upy The materials contain two separated phases: „soft blocks“ of semicrystalline PCL and „hard blocks“ composed of interacting H-bonding units (UPy and BU) www.leibniz-inm.de https://doi.org/10.1016/j.actbio.2015.08.034 42 Study of enzymatic and oxidative degradation of PCL The material: PCL and supramolecular variants (see next slide) as electrospun fibers The enzyme solution: lipase or cholesterol esterase. These enzymes, which are present in serum and are secreted by activated macrophages, are known to cleave ester and urethane bonds. The oxidative solution comprises hydrogen peroxyde and cobalt(II) chloride, which create hydroxyl radicals. PCL samples were incubated with solutions containing enzymes or oxidative agents. At several time points, chemical, morphological, and mechanical properties were investigated. www.leibniz-inm.de https://doi.org/10.1016/j.actbio.2015.08.034 43 Degradation of PCL in vitro Mass loss and molecular weight of PCL samples during enzymatic and oxidative degradation Samples were incubated in the degradation solution fir different times, washed three times with purified water, dried under vacuum at 37 °C for 16 h Mass loss due to scaffold degradation was assessed by gravimetry (weight). The molecular weight of the degraded sample was quantified by size exclusion chromatography after dissolution of the sample in DMF. Observations: PCL was mainly affected by enzymatic degradation with moderate to severe mass loss, but with stable molecular weight. The supramolecular PCL materials were mostly affected by oxidative degradation, with mass loss as well as decreases in molecular weight. www.leibniz-inm.de https://doi.org/10.1016/j.actbio.2015.08.034 44 Degradation of PCL in vitro Microscopy analysis of degradation SEM images of PCL fibers before (A–D) and after enzymatic (E–L) and oxidative (M–P) degradation. PCL is mainly affected by enzymatic degradation, resulting in thinner and clearly affected fibers. The supramolecular materials are mainly affected by oxidative degradation with thinner fibers. The fiber surface of the supramolecular materials seems less affected compared to PCL, though more fragmented fibers were observed. White scale bars represent 20 μm. www.leibniz-inm.de https://doi.org/10.1016/j.actbio.2015.08.034 45 Degradation of PCL in vitro Quantification of SEM images Scaffold fiber morphology and average fiber diameters were assessed and determined by scanning electron microscope (SEM) of the different samples at different time points. Average fiber diameters were determined by 20 individual measurements performed on four SEM images per sample. Observations: PCL mainly affected by enzymatic degradation, with moderate to severe diameter reduction depending on enzyme nature. Enzymatic degradation did not affect the fiber diameter of PCL-UPy materials and moderately reduced the diameter of PCL2000-BU fibers Oxidative degradation did not affect PCL fibers but reduced the diameter of PCL- Upy fibers. Surface of PCL is roughened after treatment. Surface of supramolecular PCL fibers is not visibly roughened but more fragmented fibers were observed www.leibniz-inm.de https://doi.org/10.1016/j.actbio.2015.08.034 46 Degradation of PCL in vitro Mechanical properties of PCL materials after enzymatic and oxidative degradation Uniaxial tensile tests were performed. Stress-strain curves were obtained (not shown) The elasticity modulus (Young’s-modulus) was determined as the slope of the initial linear part of the curve, as a measure for stiffness. As a measure for strength, the ultimate tensile strength (UTS) was defined as the peak stress value. The strain at break is a measure for the maximal elongation of the samples before breaking. Observations: PCL properties were affected by enzymatic degradation and represented by overall weakening. The mechanical properties of the supramolecular PCL materials were affected by enzymatic degradation, but to a larger extent by oxidative degradation. A change to a more brittle material was observed in supramolecular PCL after oxidation: increased Young’s modulus and reduction in strain at break. This change may be caused by annealing of the material at 37 °C during the experiment, resulting in a material with an increased crystallinity of the PCL phase, and thus a more brittle material. www.leibniz-inm.de https://doi.org/10.1016/j.actbio.2015.08.034 47 Mechanical properties (previous lecture) Measurement principles Tensile test Plastic deformation Irreversible, dissipative process, 𝐴0 contrary to elastic deformation Ultimate 𝑙0 elongation 𝐸 𝐸: Young‘s modulus 𝜎𝑦 : yield strength 𝜀𝑦 : yield elongation(*)/ Displacement- or stress-controlled elongation(*) at yield Different deformation rates 𝜎𝑓 : ultimate strength Usually (but not necessarily) rectangular specimen cross-section 𝜀𝑓 : ultimate elongation(*)/ Optical, mechanical or electrical strain measurement elongation(*) at break (*) misleading naming convention. Elongation ≠ Strain. www.leibniz-inm.de 48 Study of enzymatic and oxidative degradation of PCL materials Summary of results The susceptibility of each material to enzymatic as well as oxidative degradation is represented by a color scale. The PCL scaffolds were rapidly degraded by enzymatic hydrolysis, using lipase or cholesterol esterase, as evidenced by mass loss, changes in fiber morphology, and overall weakening, while molecular weight remained unaffected. The supramolecular PCL-UPy- and PCL-BU are less prone to hydrolyze enzymatically, with no or minimal changes in mass, molecular weight and fiber diameter. The introduction of the BU or UPy hard blocks in the polycaprolactone backbone has a marked stabilizing effect against enzymatic degradation. The supramolecular materials are https://doi.org/10.1016/j.actbio.2015.08.034 susceptible to oxidative degradation. www.leibniz-inm.de 49