| 1. |
- Ahlinder, Astrid, et al.
(author)
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Medical grade polylactide, copolyesters and polydioxanone : Rheological properties and melt stability
- 2018
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In: Polymer testing. - : ELSEVIER SCI LTD. - 0142-9418 .- 1873-2348. ; 72, s. 214-222
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Journal article (peer-reviewed)abstract
- Rheological measurements have shown that lactide-based copolymers with L-lactide content between 50 and 100 mol% with varying comonomers, as well as polydioxanone (PDX), can be used in additive manufacturing analogously to poly(L-lactide) (PLLA) if their melt behaviour are balanced. The results indicate that copolymers can be melt processed if the temperature is adjusted according to the melting point, and parameters such as the speed are tuned to conteract the elastic response. Small amplitude oscillatory shear (SAOS) rheology, thermal and chemical characterisation allowed us to map the combined effect of temperature and frequency on the behaviour of six degradable polymers and their melt stability. Values of complex viscosity and Tan delta obtained through nine time sweeps by varying temperature and frequency showed that the molecular structure and the number of methylene units influenced the results, copolymers of L-lactide with D-Lactide (PDLLA) or glycolide (PLGA) had an increased elastic response, while copolymers with trimethylene carbonate (PLATMC) or epsilon-caprolactone (PCLA) had a more viscous behaviour than PLLA, with respect to their relative melting points. PDLLA and PLGA require an increased temperature or lower speed when processed, while PLATMC and PCLA can be used at a lower temperature and/or higher speed than PLLA. PDX showed an increased viscosity compared to PLLA but a similar melt behaviour. Negligible chain degradation were observed, apart from PLGA.
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| 2. |
- Bartaula-Brevik, Sushma, et al.
(author)
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Angiogenic and Immunomodulatory Properties of Endothelial and Mesenchymal Stem Cells
- 2016
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In: Tissue Engineering. Part A. - : Mary Ann Liebert. - 1937-3341 .- 1937-335X. ; 22:3-4, s. 244-252
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Journal article (peer-reviewed)abstract
- It has been suggested that the effect of implanted cells on the local environment is important when selecting the appropriate cell type for tissue regeneration. Our aim was to compare the local tissue response to implanted human mesenchymal stem cells (MSC) and human umbilical vein endothelial cells (EC). MSC and EC were cultured in poly(l-lactide-co-1,5-dioxepan-2-one) scaffolds for 1 week in a bioreactor system, after which they were implanted subcutaneously in NOD/SCID mice. After 3 weeks, scaffolds were retrieved, and the mRNA expression of selected genes involved in hypoxia and inflammation was examined by real-time reverse transcription polymerase chain reaction and correlated with immunofluorescent staining for corresponding proteins. The Toll-like receptor signaling pathway was examined by superarray hybridization. The expression of 53 angiogenesis-related proteins was investigated by a proteome profiler angiogenesis antibody array kit. Vascularization was quantified using immunohistochemistry for CD31. The expression of hypoxia-inducible factors and biomarkers for angiogenesis was more strongly upregulated in response to implanted EC than to MSC, suggesting a higher sensitivity to low oxygen tension among EC. Hypoxic signaling was increased after implantation of EC compared with MSC, leading to a prolonged acute inflammatory phase that promoted ingrowth of vascular cells and establishment of the circulation. Inflammatory cytokines were also differently expressed at the gene and protein levels in the two experimental groups, resulting in altered recruitment of acute and chronic inflammatory cells. The end result of these differences was increased vessel formation within the constructs in the EC group.
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| 3. |
- Fagerland, Jenny, et al.
(author)
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Modulating the thermal properties of poly(hydroxybutyrate) by the copolymerization of rac-beta-butyrolactone with lactide
- 2016
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In: New Journal of Chemistry. - : Royal Society of Chemistry. - 1144-0546 .- 1369-9261. ; 40:9, s. 7671-7679
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Journal article (peer-reviewed)abstract
- Biobased poly(hydroxybutyrate) is produced by microorganisms under controlled conditions. It is a linear, high molecular weight, fully isotactic and highly crystalline polymer. However, it has poor mechanical and thermal properties. We have modulated the thermal properties of this material by ring-opening co-polymerization of rac-beta-butyrolactone (BL) with lactide (LA) in the presence of salan-based yttrium and aluminum catalysts. The prepared poly(hydroxybutyrate-co-lactide) copolymers were characterized by proton and carbon nuclear magnetic resonance (H-1 and C-13 NMR), size exclusion chromatography (SEC) and differential scanning calorimetry (DSC) analyses. The salan-yttrium compound was a more effective catalyst compared to the aluminum compound, affording high molecular weight copolymers with higher monomer conversion and a monomodal distribution of the molecular weights. The kinetic experiments showed a higher rate of polymerization for the LA with respect to the BL. The copolymers were amorphous and DSC showed unique transition temperatures for all of the samples. The formation of a gradient copolymer is proposed.
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| 4. |
- Fagerland, Jenny, 1985-
(author)
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Synthesis of degradable aliphatic polyesters: strategies to tailor the polymer microstructure
- 2018
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Doctoral thesis (other academic/artistic)abstract
- Key factors for successful tissue engineering are the synthesis and design of the scaffold materials. Aliphatic polyesters have been studied and often used as scaffold materials for tissue engineering. However, their lack of biological cues and degradation under high-temperature processing (e.g., 3D printing) are a limitation. In this thesis, different synthesis strategies are presented which has the potential to improve the performance of aliphatic polyesters as scaffolds for tissue regeneration.To stimulate interactions between exogenous materials and the surrounding tissue, two different strategies were applied. Either, by designing a two component system in which the different degradation profiles of the polymers allow for sequential release of growth factors. Or, by peptide functionalization of an aliphatic polyester chain using template-assisted chemo-enzymatic synthesis. The results from the studies were successful. A hierarchical system was obtained in which the poly(L-lactide-co-glycolide)-graft-poly(ethylene glycol) methyl ether (PLGA-g-MPEG), hydroxyapatite solution formed a gel around and within the pores of the poly(L-lactide-co-ε-caprolactone) scaffold at 37 ºC, within 1 min, that was stable for 3 weeks. The peptide functionalization was also successful where an aliphatic polyester of L-lactide was functionalized with different oligopeptides using a grafter (ethyl hept-6-enoylalaninate) and chemo-enzymatic synthesis.The thermal properties of poly(L-lactide-co-hydroxybutyrate) were tailored (by modification of the microstructure) to potentially improve the processability of the aliphatic polyester. The results showed that the yttrium salan catalyst was the most successful, yielding high molecular weight copolymers in shorter time. They also showed that the Tg could be tailored by varying the amount of rac-β-butyrolactone in the copolymer to better suit thermal processing techniques, such as 3D printing.
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| 5. |
- Fagerland, Jenny, 1985-, et al.
(author)
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Template-assisted enzymatic synthesis of oligopeptides from a polylactide chain
- 2017
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In: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 18:12, s. 4271-4280
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Journal article (peer-reviewed)abstract
- Peptides are often attached to polymer materials, as bioactive components, for the control of interactions between the material and its surrounding proteins and cells. However, synthesizing peptides and attaching them to polymers can be challenging and laborious. Herein, we describe the grafting of oligopeptides to an aliphatic polyester, using a one-step chemo-enzymatic synthesis with papain as the biocatalySt. To enable enzyme-mediated functionalization of the polyester, ethyl hept-6-enoylalaninate (grafter) was synthesized and attached to polylactide chains using thiol-ene click reactions. The oligopeptides were grafted onto the polylactide chains using two different synthetic routes: the grafting from strategy, in which the grafter was attached to the polyester prior to oligopeptide synthesis, or the grafting to strategy, in which oligopeptides were synthesized on the grafter first, then attached to the polymer chain. The final products were analyzed and their structures were confirmed using nuclear magnetic resonance (NMR). The peptide attachment was evaluated using size exclusion chromatography (SEC), contact angle measurement and energy-dispersive X-ray spectroscopy scanning electron microscopy (EDS-SEM). Furthermore, the mechanistic aspects of the synthesis of the oligopeptides on the grafter were studied using molecular dynamics (MD) simulations. The simulation revealed that hydrogen bonding (between the P1 amide nitrogen of the grafter backbone and the carbonyl oxygen of D158 in the papain) maintain the grafter in a productive conformation to stabilize the transition state of nitrogen inversion, a key step of the biocatalytic mechanism. Apart from being biologically relevant, both experimental and computational results suggest that the designed grafter is a good template for initiating chemo-enzymatic synthesis. The results also showed that the grafting to strategy was more successful compared to the grafting from strategy. Overall, a successful synthesis of predefined peptide functionalized polylactide was prepared, where the oligopeptides were grafted in an easy, time efficient, and environmentally friendly way.
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| 6. |
- Fuoco, Tiziana, et al.
(author)
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A Route to Aliphatic Poly(ester)s with Thiol Pendant Groups : From Monomer Design to Editable Porous Scaffolds
- 2016
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In: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 17:4, s. 1383-1394
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Journal article (peer-reviewed)abstract
- Biodegradable aliphatic polyesters such as poly(lactide) and poly(ϵ-caprolactone), largely used in tissue engineering applications, lack suitable functional groups and biological cues to enable interactions with cells. Because of the ubiquity of thiol groups in the biological environment and the pliability of thiol chemistry, we aimed to design and synthesize poly(ester) chains bearing pendant thiol-protected groups. To achieve this, 3-methyl-6-(tritylthiomethyl)-1,4-dioxane-2,5-dione, a lactide-type monomer possessing a pendant thiol-protected group, was synthesized. This molecule, when used as a monomer in controlled ring-opening polymerization in combination with lactide and ϵ-caprolactone, appeared to be a convenient "building block" for the preparation of functionalized aliphatic copolyesters, which were easily modified further. A polymeric sample bearing pyridyl disulfide groups, able to bind a cysteine-containing peptide, was efficiently obtained from a two-step modification reaction. Porous scaffolds were then prepared by blending this latter copolymer sample with poly(l-lactide-co-ϵ-caprolactone) followed by salt leaching. A further disulfide exchange reaction performed in aqueous medium formed porous scaffolds with covalently linked arginine-glycine-aspartic acid sequences. The scaffolds were characterized by thermal and mechanical tests, and scanning electron microscopy surface images revealed a highly porous morphology. Moreover, a cytotoxicity test indicated good cell viability.
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| 7. |
- Fuoco, Tiziana, PhD, 1986-, et al.
(author)
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Enhancing the Properties of Poly(epsilon-caprolactone) by Simple and Effective Random Copolymerization of epsilon-Caprolactone with p-Dioxanone
- 2019
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In: Biomacromolecules. - : AMER CHEMICAL SOC. - 1525-7797 .- 1526-4602. ; 20:8, s. 3171-3180
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Journal article (peer-reviewed)abstract
- We have developed a straightforward strategy to obtain semicrystalline and random copolymers of epsilon-caprolactone (CL) and p-dioxanone (DX) with thermal stabilities similar to poly(epsilon-caprolactone), PCL, but with a faster- hydrolytic degradation rate-CL/DX-copolymers-are promising inks when printing scaffolds aimed for tissue engineering. Such copolymers behave similar to PCL and resorb faster. The copolymers were synthesized by bulk ring-opening copolymerization, achieving a high yield; a molecular weight, M-n, of 57-176 kg mol(-1); and an inherent viscosity of 1.7-1.9 dL g(-1). The copolymer microstructure consisted of long CL blocks that are separated by isolated DX units. The block length and the melting point were a linear function of the DX content. The copolymers crystallize as an orthorhombic lattice that is typical for PCL, and they formed more elastic, softer, and less hydrophobic films with faster degradation rates than PCL. Relatively high thermal degradation temperatures (above 250 C), similar to PCL, were estimated by thermogravimetric analysis, and copolymer filaments for three-dimensional printing and scaffolds were produced without thermal degradation.
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| 8. |
- Fuoco, Tiziana, PhD, 1986-, et al.
(author)
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Minimizing the time gap between service lifetime and complete resorption of degradable melt-spun multifilament fibers
- 2019
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In: Polymer degradation and stability. - : Elsevier. - 0141-3910 .- 1873-2321. ; 163, s. 43-51
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Journal article (peer-reviewed)abstract
- We have succeeded to modulated the degradation rate of poly(L-lactide) (PLLA) melt-spun multifilament fibers to extend the service lifetime and increase the resorption rate by using random copolymers of L-lactide and trimethylene carbonate (TMC). The presence of TMC units enabled an overall longer service lifetime but faster degradation kinetics than PLLA. By increasing the amount of TMC up to 18 mol%, multifilament fibers characterized by a homogenous degradation profile could be achieved. Such composition allowed, once the mechanical integrity was lost, a much longer retention of mechanical integrity and a faster rate of mass loss than samples containing less TMC. The degradation profile of multifilament fibers consisting of (co)polymers containing 0, 5, 10 and 18 mol% of TMC has been identified during 45 weeks in vitro hydrolysis following the molecular weight decrease, mass loss and changes in microstructure, crystallinity and mechanical properties. The fibers degraded by a two-step, autocatalyzed bulk hydrolysis mechanism. A high rate of molecular weight decrease and negligible mass loss, with a consequent drop of the mechanical properties, was observed in the early stage of degradation for fibers having TMC content up to 10 mol%. The later stage of degradation was, for these samples, characterized by a slight increase in the mass loss and a negligible molecular weight decrease. Fibers prepared with the 18 mol% TMC copolymer showed instead a more homogenous molecular weight decrease ensuring mechanical integrity for longer time and faster mass loss during the later stage of degradation.
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| 9. |
- Fuoco, Tiziana, PhD, 1986-, et al.
(author)
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Poly(L-lactide) and Poly(L-lactide-co-trimethylene carbonate) Melt-Spun Fibers : Structure-Processing-Properties Relationship
- 2019
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In: Biomacromolecules. - : AMER CHEMICAL SOC. - 1525-7797 .- 1526-4602. ; 20:3, s. 1346-1361
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Journal article (peer-reviewed)abstract
- l-Lactide/trimethylene carbonate copolymers have been produced as multifilament fibers by high-speed melt-spinning. The relationship existing between the composition, processing parameters and physical properties of the fibers has been disclosed by analyzing how the industrial process induced changes at the macromolecular level, i.e., the chain microstructure and crystallinity development. A poly(l-lactide) and three copolymers having trimethylene carbonate contents of 5, 10 and 18 mol % were synthesized with high molecular weight (M n ) up to 377 kDa and narrow dispersity. Their microstructure, crystallinity and thermal properties were dictated by the composition. The spinnability was then assessed for all the as-polymerized materials: four melt-spun multifilament fibers with increasing linear density were collected for each (co)polymer at a fixed take-up speed of 1800 m min -1 varying the mass throughput during the extrusion. A linear correlation resulted between the as-spun fiber properties and the linear density. The as-spun fibers could be further oriented, developing more crystallinity and improving their tensile properties by a second stage of hot-drawing. This ability was dependent on the composition and crystallinity achieved during the melt-spinning and the parameters selected for the hot-drawing, such as temperature, draw ratio and input speed. The crystalline structure evolved to a more stable form, and the degree of crystallinity increased from 0-52% to 25-66%. Values of tensile strength and Young's modulus up to 0.32-0.61 GPa and 4.9-8.4 GPa were respectively achieved.
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| 10. |
- Fuoco, Tiziana, et al.
(author)
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Redox-Responsive Disulfide Cross-Linked PLA-PEG Nanoparticles
- 2017
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In: Macromolecules. - : AMER CHEMICAL SOC. - 0024-9297 .- 1520-5835. ; 50:18, s. 7052-7061
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Journal article (peer-reviewed)abstract
- We have developed a strategy for the preparation of redox-responsive PEG PLA-based nanoparticles containing disulfide bonds that can be disassembled in the presence of cellular concentrations of glutathione. Functionalized poly-(lactide)s were prepared by ring-opening copolymerization of L-lactide and 3-methyl-6-(tritylthiomethyl)-1,4-dioxane-2,5-dione, a monomer bearing a pendant trityl-thiol group, followed by the postpolymerization modification of trityl-thiol into pyridyl disulfide groups. Polymeric networks composed of PLA and PEG blocks linked by disulfide bonds were prepared by a disulfide exchange reaction between the functionalized PLAs and telechelic PEG having thiol groups at both ends, HS-PEG-SH, in DMF. When dialyzed against water, they assembled into dispersible nanoparticles, with a flowerlike structure having a hydrophobic core and a hydrophilic shell, with sizes in the range 167-300 nm that are suitable for drug delivery. The effects of the number of functional groups, molecular weight, and concentration on the nanoparticle size were evaluated. The stability of the nanoparticles after dilution and the redox-responsive behavior in the presence of different concentrations of glutathione were assessed. The hydrophobic molecule Nile red could be encapsulated in the nanoparticles and then released in the presence of glutathione at cellular concentration.
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