1. |
- Fuoco, Tiziana, PhD, 1986-, et al.
(author)
-
Capturing the Real-Time Hydrolytic Degradation of a Library of Biomedical Polymers by Combining Traditional Assessment and Electrochemical Sensors
- 2021
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In: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 22:2, s. 949-960
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Journal article (peer-reviewed)abstract
- We have developed an innovative methodology to overcome the lack of techniques for real-time assessment of degradable biomedical polymers at physiological conditions. The methodology was established by combining polymer characterization techniques with electrochemical sensors. The in vitro hydrolytic degradation of a series of aliphatic polyesters was evaluated by following the molar mass decrease and the mass loss at different incubation times while tracing pH and L-lactate released into the incubation media with customized miniaturized electrochemical sensors. The combination of different analytical approaches provided new insights into the mechanistic and kinetics aspects of the degradation of these biomedical materials. Although molar mass had to reach threshold values for soluble oligomers to be formed and specimens' resorption to occur, the pH variation and L-lactate concentration were direct evidence of the resorption of the polymers and indicative of the extent of chain scission. Linear models were found for pH and released L-lactate as a function of mass loss for the Llactide-based copolymers. The methodology should enable the sequential screening of degradable polymers at physiological conditions and has potential to be used for preclinical material's evaluation aiming at reducing animal tests.
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2. |
- Ahlinder, Astrid
(author)
-
Degradable copolymers in additive manufacturing: controlled fabrication of pliable scaffolds
- 2021
-
Doctoral thesis (other academic/artistic)abstract
- Inom vävnadsregenerering är produktionen av väldefinieradematriser med en porös arkitektur av nedbrytbara polymerer av stortintresse, dessa kan nu skapas genom additiva tillverkningsprocesser. Vidadditiv tillverkning krävs ett smalt munstycke för att skapa detaljrikastrukturer och detta ställer krav på att de reologiska egenskapernaanpassat. Lägre viskositet av smältan gör de lättare att använda, men enhög molmassa krävs för tillverka matriser där de mekaniska egenskapernakan bibehållas under tiden som krävs för vävnadsregenerering. Ytterligareen utmaning uppstår när nedbrytbara polymerer används i smältbaseradadditiva tillverkningsprocesser är att termisk nedbrytning ofta reducerarmolmassan redan under produktionsfasen. För att kunna användanedbrytbara polymerer av medicinsk kvalitet i smältbaserad additivtillverkning och samtidigt minimera den termiska nedbrytningen har, idenna avhandling, reologiska fingeravtryck av nedbrytbara syntetiskapolymerer med medicinsk kvalitet använts för att bestämmaprocessparametrar. Termisk nedbrytning beroende av processparamaterar har analyserats och minimeras i två smältbaserade additivatillverkningsprocesser.En additiv tillverkningsprocess var designad där nedbrytbarapolymerer av hög molmassa kunde användas utan termisk nedbrytning närprocessparametrar hade valts utifrån polymerens egenskaper. Kunskapenom användningen av dessa polymerer inom additiv tillverkning kundeappliceras på en sampolymer som utvecklats inom forskningsgruppen förmjukvävnad, poly(ε-kaprolakton-co-p-dioxanon) för att skapa böjbaramatriser. Genom att använda reologisk analys och polymerkarakteriseringerhölls processparametrar som möjliggjorde additiv tillverkning utantermisk nedbrytning. I tillägg till val av polymer och processparametrar såkan mekaniska egenskaper också styras av den strukturella designen.Poly(ε-kaprolakton) användes som modellmaterial för att reducerastyvheten med hjälp av designen, resultatet visade att det var möjligt medmer än en faktor 10 och mjuka böjbara matriser skapades.
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3. |
- Ahlinder, Astrid, et al.
(author)
-
Minimise thermo-mechanical batch variations when processing medical grade lactide based copolymers in additive manufacturing
- 2020
-
In: Polymer degradation and stability. - : Elsevier BV. - 0141-3910 .- 1873-2321. ; 181
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Journal article (peer-reviewed)abstract
- Additive manufacturing is suitable for producing complex geometries; however, variation in thermo-mechanical properties are observed during one batch cycle when degradable aliphatic polyesters of medical grade are used in melt extrusion-based methods. This is one important reason for why additive manufacturing has not yet been fully utilised to produce degradable medical implants. Herein, the internal variation has been minimised during one batch cycle by assessing the effect of different processing parameters when using commercially available medical grade copolymers. To minimise the molar mass, thermal and mechanical variation within one batch cycle, the rheological fingerprint of the commercially available medical grade poly(L-lactide-co-ε-caprolactone) and poly(L-lactide-co-trimethylene carbonate) has been correlated to the process parameters of the ARBURG Plastic Freeforming. An increase in the temperature up to 220°C and the associated increase in pressure are beneficial for the viscoelastic and thermally stable poly(L-lactide-co-ε-caprolactone). In contrast, a temperature below 220°C should be used for the poly(L-lactide-co-trimethylene carbonate) to reduce the variation in strain at break during one batch cycle. The residence time is decreased through the increase of the discharge parameter. An increase in temperature is however required to reduce the viscosity of the polymer and allow the pressure to stay within the machine limitations at higher discharge parameters. The results are highly relevant to the development of additive manufacturing for the production of degradable medical devices with identical properties. In fact, Food and Drug Administration guidelines for additive manufacturing of medical implants specify the need to control changes in material properties during the process.
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4. |
- Ahlinder, Astrid, et al.
(author)
-
Nondegradative additive manufacturing of medical grade copolyesters of high molecular weight and with varied elastic response
- 2020
-
In: Journal of Applied Polymer Science. - : WILEY. - 0021-8995 .- 1097-4628. ; 137:15
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Journal article (peer-reviewed)abstract
- Although additive manufacturing through melt extrusion has become increasingly popular as a route to design scaffolds with complex geometries the technique if often limited by the reduction in molecular weight and the viscoelastic response when degradable aliphatic polyesters of high molecular weight are used. Here we use a melt extruder and fused filament fabrication printer to produce a reliable nondegradative route for scaffold fabrication of medical grade copolymers of L-lactide, poly(epsilon-caprolactone-co-L-lactide), and poly(L-lactide-co-trimethylene carbonate). We show that degradation is avoided using filament extrusion and fused filament fabrication if the process parameters are deliberately chosen based upon the rheological behavior, mechanical properties, and polymer composition. Structural, mechanical, and thermal properties were assessed throughout the process to obtain comprehension of the relationship between the rheological properties and the behavior of the medical grade copolymers in the extruder and printer. Scaffolds with a controlled architecture were achieved using high-molecular-weight polyesters exhibiting a large range in the elastic response causing negligible degradation of the polymers.
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5. |
- Andriani, Fika, et al.
(author)
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Statistical enchainment of ester/ether and carbonate cleavable bonds to control copolymers? : erosion rate and trigger environment-specific degradation
- 2022
-
In: European Polymer Journal. - : Elsevier BV. - 0014-3057 .- 1873-1945. ; 178, s. 111457-
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Journal article (peer-reviewed)abstract
- Polymers containing ester bonds undergo abiotic degradation independently from the surrounding environment as long as the hydrolytic conditions are provided. The hydrolysis of the ester bonds leads a bulk degradation of the polymeric matrix which, contrary to surface erosion, is unpredictable. The enchainment of diverse degradability functions was sought to expand the scope of the degradation mechanism and achieve a more predictable profile of the mass loss.The copolymerization of trimethylene carbonate and p-dioxanone enabled the synthesis of one class of copolymers with controllable erosion rate and susceptible to three degradation pathways depending on the surrounding environment. The synthetic strategy used organocatalysts and allowed the synthesis at room temperature of both random and block copolymers in high yield and with molar mass, Mn, in the range 12-22 kg mol- 1. The composition and microstructure of the random copolymers were regulated by varying the monomers' ratio. Diverse cleavable groups, i.e., ester/ether and carbonate bonds, were statistically incorporated along the same polymer chain to yield materials able to degrade under hydrolytic, oxidative and enzymatic conditions. Bulk degradation was the mechanism that took place under hydrolytic conditions, while the oxidative and enzymatic environments lead to surface erosion. The rate of mass loss of the random copolymers was regulated by varying the composition. These results showed how the statistical incorporation of different degradable bonds could pave the way to diverse and more predictable degradation pathways than simple hydrolysis by taking advantages of the surrounding environment to trigger surface erosion.
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6. |
- Fuoco, Tiziana, PhD, 1986-
(author)
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Degradation in Order : Simple and Versatile One-Pot Combination of Two Macromolecular Concepts to Encode Diverse and Spatially Regulated Degradability Functions
- 2021
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In: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 60:28, s. 15482-15489
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Journal article (peer-reviewed)abstract
- The clever one-pot combination of two macromolecular concepts, ring-opening polymerization (ROP) and step-growth polymerization (SGP), is demonstrated to be a simple, yet powerful tool to design a library of sequence-controlled polymers with diverse and spatially regulated degradability functions. ROP and SGP occur sequentially at room temperature when the organocatalytic conditions are switched from basic to acidic, and each allows the encoding of specific degradable bonds. ROP controls the sequence length and position of the degradability functions, while SGP between the complementary vinyl ether and hydroxyl chain-ends enables the formation of acetal bonds and high-molar-mass copolymers. The result is the rational combination of cleavable bonds prone to either bulk or surface erosion within the same macromolecule. The strategy is versatile and offers higher chemical diversity and level of control over the primary structure than current aliphatic polyesters or polycarbonates, while being simple, effective, and atom-economical and having potential for scalability.
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7. |
- Fuoco, Tiziana, PhD, 1986-, et al.
(author)
-
Enhancing the Properties of Poly(epsilon-caprolactone) by Simple and Effective Random Copolymerization of epsilon-Caprolactone with p-Dioxanone
- 2019
-
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)
-
Hydrogel Polyester Scaffolds via Direct-Ink-Writing of Ad Hoc Designed Photocurable Macromonomer
- 2022
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In: Polymers. - : MDPI. - 2073-4360. ; 14:4
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Journal article (peer-reviewed)abstract
- Synthetic, degradable macromonomers have been developed to serve as ink for 3D printing technologies based on direct-ink-writing. The macromonomers are purposely designed to be cross-linkable under the radical mechanism, to impart hydrophilicity to the final material, and to have rheological properties matching the printer's requirements. The suitable viscosity enables the ink to be printed at room temperature, in absence of organic solvents, and to be cross-linked to manufacture soft 3D scaffolds that show no indirect cytotoxicity and have a hydration capacity of up to 100% their mass and a compressive modulus in the range of 0.4-2 MPa.
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9. |
- Fuoco, Tiziana, PhD, 1986-, et al.
(author)
-
Minimizing the time gap between service lifetime and complete resorption of degradable melt-spun multifilament fibers
- 2019
-
In: Polymer degradation and stability. - : Elsevier. - 0141-3910 .- 1873-2321. ; 163, s. 43-51
-
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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10. |
- Fuoco, Tiziana, PhD, 1986-, et al.
(author)
-
Multipurpose Degradable Physical Adhesive Based on Poly(d,l-lactide-co-trimethylene Carbonate)
- 2020
-
In: Macromolecular Chemistry and Physics. - : Wiley. - 1022-1352 .- 1521-3935. ; 221:10
-
Journal article (peer-reviewed)abstract
- Solutions of amorphous poly(d,l-lactide-co-trimethylene carbonate)s (PDLTMCs) in ethyl acetate work as solvent-based physical adhesives through diffusion mechanisms for a variety of aliphatic polyester-based adherents. The random PDLTMCs with a trimethylene carbonate content of 11, 16, and 20 mol% are synthesized in bulk, achieving high molecular weight, M-n, up to 128 kg mol(-1) and dispersity around 1.7. The PDLTMCs are amorphous and have a glass transition temperature in the range 34.7 to 43.6 degrees C and in agreement with the theoretical values calculated using the Fox equation. The mechanical and surface properties of the PDLTMCs are tested preparing solvent cast films, which are soft and tough and, although they have a higher contact angle than the parent homopolymer, they show higher water uptake capacity. The potential application as adhesives of the synthesized PDLTMCs is evaluated by preparing a 20 wt% solution in ethyl acetate and testing them by adhering films with different compositions as well as constructs having different geometries and surface roughness. The results demonstrate that the adhesion strength is higher on adherent films having similar chemical compositions as the adhesives and on surfaces having similar compositions to each other but different roughness. The similar chemical nature of the adhesive and adherent probably favors the diffusion mechanism through which adhesion takes place.
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11. |
- Fuoco, Tiziana, PhD, 1986-, et al.
(author)
-
Organocatalytic strategy to telechelic oligo(ε-caprolactone-co-p-dioxanone): Photocurable macromonomers for polyester networks
- 2020
-
In: European Polymer Journal. - : Elsevier BV. - 0014-3057 .- 1873-1945. ; 141
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Journal article (peer-reviewed)abstract
- We have designed photocurable, telechelic macromonomers consisting of random oligo(ε-caprolactone-co-p-dioxanone), oligo(CL-co-DX), and demonstrated their suitability for preparing pliable polyester networks whose properties resemble those of gels.A versatile and effective metal-free co-oligomerization, catalyzed by diphenyl phosphate, was developed in bulk and at room temperature. A high rate of conversion of monomers was achieved and oligo(CL-co-DX)s with different composition and topology were obtained with controlled molar mass, approx. 2000 g mol−1, low dispersity and a random distribution of the two monomeric units. Kinetics analysis of the reaction disclosed a faster incorporation rate for the p-dioxanone (DX) than ε-caprolactone (CL). The extrapolated rate constant, kDX, was 0.030 min−1 against a kCL of 0.013 min−1. The reactivity ratios were respectively 2.7 (rDX) and 0.28 (rCL). A detailed NMR analysis was performed to elucidate the structure of the co-oligomers, which could be precisely controlled by varying the monomer feed ratio and initiator. Depending on the composition, amorphous to semicrystalline oligomers with melting points close to room temperature were obtained, which after acrylation of the chain-end gave polyester networks with high swelling capacity up to 700%, and water uptake up to 70%.
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12. |
- Fuoco, Tiziana, PhD, 1986-, et al.
(author)
-
Poly(epsilon-caprolactone-co-p-dioxanone) : a Degradable and Printable Copolymer for Pliable 3D Scaffolds Fabrication toward Adipose Tissue Regeneration
- 2020
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In: Biomacromolecules. - : AMER CHEMICAL SOC. - 1525-7797 .- 1526-4602. ; 21:1, s. 188-198
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Journal article (peer-reviewed)abstract
- The advancement of 3D printing technologies in the fabrication of degradable scaffolds for tissue engineering includes, from the standpoint of the polymer chemists, an urgent need to develop new materials that can be used as ink and are suitable for medical applications. Here, we demonstrate that a copolymer of epsilon-caprolactone (CL) with low amounts of p-dioxanone (DX) (15 mol %) is a degradable and printable material that suits the requirements of melt extrusion 3D printing technologies, including negligible degradation during thermal processing. It is therefore a potential candidate for soft tissue regeneration. The semicrystalline CL/DX copolymer is processed at a lower temperature than a commercial polycaprolactone (PCL), shaped as a filament for melt extrusion 3D printing and as porous and pliable scaffolds with a gradient design. Scaffolds have Young's modulus in the range of 60-80 MPa, values suitable for provision of structural support for damaged soft tissue such as breast tissue. SEM and confocal microscope indicate that the CL/DX copolymer scaffolds support adipose stem cell attachment, spreading, and proliferation.
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13. |
- Fuoco, Tiziana, PhD, 1986-, et al.
(author)
-
Poly(L-lactide) and Poly(L-lactide-co-trimethylene carbonate) Melt-Spun Fibers : Structure-Processing-Properties Relationship
- 2019
-
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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14. |
- Fuoco, Tiziana, PhD, 1986-, et al.
(author)
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Synthetic Approaches to Combine the Versatility of the Thiol Chemistry with the Degradability of Aliphatic Polyesters
- 2020
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In: POLYMER REVIEWS. - : TAYLOR & FRANCIS INC. - 1558-3724 .- 1558-3716. ; 60:1, s. 86-113
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Journal article (peer-reviewed)abstract
- We consider optimal sensor scheduling with unknown communication channel statistics. We formulate two types of scheduling problems with the communication rate being a soft or hard constraint, respectively. We first present some structural results on the optimal scheduling policy using dynamic programming and assuming that the channel statistics is known. We prove that the Q-factor is monotonic and submodular, which leads to threshold-like structures in both problems. Then we develop a stochastic approximation and parameter learning frameworks to deal with the two scheduling problems with unknown channel statistics. We utilize their structures to design specialized learning algorithms. We prove the convergence of these algorithms. Performance improvement compared with the standard Q-learning algorithm is shown through numerical examples, which also discuss an alternative method based on recursive estimation of the channel quality.
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15. |
- Hirschmann, Max, et al.
(author)
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Bi-functional and mono-component organocatalysts for the ring-opening alternating co-polymerisation of anhydride and epoxide
- 2023
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In: Catalysis Science & Technology. - : Royal Society of Chemistry (RSC). - 2044-4753 .- 2044-4761. ; 13:24, s. 7011-7021
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Journal article (peer-reviewed)abstract
- Bi-functional organocatalysts constituted by a (thio-)urea moiety and an iminophosphorane moiety were synthesized and optimised for the ring-opening alternating co-polymerisation of phthalic anhydride with three different epoxides: cyclohexene oxide, propylene oxide and butylene oxide. The most effective catalyst featured a cyclohexyl urea moiety, an iminophosphorane moiety with three 2,4-dimethyl-3-methoxy phenyl substituents, and a short spacer length of two carbon atoms between them. All tested epoxides reached quantitative conversion within 24 hours with ester-selectivities up to >97%. NMR and DFT experiments reveal that the catalysts exist in solution as dimers that dissociate during the initiation of the polymerisation. During the polymerisation, the catalyst is coordinated to the growing chain and further modulates its reactivity through reversible protonation/deprotonation suppressing transesterification side reactions even at prolonged polymerisation times without the need for a co-catalyst. The rate-determining step of the polymerisation is the ring-opening of the epoxide by the carboxylate chain end, and accordingly, higher temperatures (up to 150 °C) and higher concentrations of epoxide and catalyst increase polymerisation rates.
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16. |
- Hirschmann, Max, et al.
(author)
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Functional and degradable copolyesters by ring-opening copolymerization of and
- 2023
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In: European Polymer Journal. - : Elsevier BV. - 0014-3057 .- 1873-1945. ; 183
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Journal article (peer-reviewed)abstract
- The ring-opening copolymerization (ROcoP) of epoxides and anhydrides is exploited to afford 4 structurally diverse and functional copolyesters. Mixtures of 2 epoxides (allyl glycidyl ether and butylene oxide) with 1 anhydride (succinic, glutaric, phthalic and homo phthalic anhydride) are copolymerized in the presence of bis (triphenylphosphine)iminium chloride (PPNCl) as organocatalyst. All monomer combinations yield vinyl-functionalized materials with alternating epoxide-anhydride units, statistical incorporation of both epoxides along the polymer chain and molar masses up to 28.3 kg/mol. The copolyesters are amorphous with a Tg between -39 degrees C and 38 degrees C. Together with the molar mass, the anhydride dictates the thermal stability of the copolyesters with glutaric anhydride resulting in a remarkably high thermal stability up to 310 degrees C. In a post-polymerization step, the pendant double bonds are radically crosslinked to gels with swelling ratios above 1500 % and com-parable to enhanced thermal stability with respect to the non-crosslinked, parent copolyesters. The degradation of the 4 copolyesters (before and after crosslinking) is tested in abiotic and enzymatic conditions: The highest degradation rates are observed for the non-crosslinked materials in enzymatic conditions with a mass loss of up to 60 % after 27 d. After crosslinking, the gels are more stable against degradation under both conditions, although a decrease in the gel content and a decrease in mass indicates that degradation still takes place.
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17. |
- Jain, Shubham, et al.
(author)
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Engineering 3D degradable, pliable scaffolds toward adipose tissue regeneration; optimized printability, simulations and surface modification
- 2020
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In: Journal of Tissue Engineering. - : SAGE Publications. - 2041-7314. ; 11
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Journal article (peer-reviewed)abstract
- We present a solution to regenerate adipose tissue using degradable, soft, pliable 3D-printed scaffolds made of a medical-grade copolymer coated with polydopamine. The problem today is that while printing, the medical grade copolyesters degrade and the scaffolds become very stiff and brittle, being not optimal for adipose tissue defects. Herein, we have used high molar mass poly(L-lactide-co-trimethylene carbonate) (PLATMC) to engineer scaffolds using a direct extrusion-based 3D printer, the 3D Bioplotter (R). Our approach was first focused on how the printing influences the polymer and scaffold's mechanical properties, then on exploring different printing designs and, in the end, on assessing surface functionalization. Finite element analysis revealed that scaffold's mechanical properties vary according to the gradual degradation of the polymer as a consequence of the molar mass decrease during printing. Considering this, we defined optimal printing parameters to minimize material's degradation and printed scaffolds with different designs. We subsequently functionalized one scaffold design with polydopamine coating and conducted in vitro cell studies. Results showed that polydopamine augmented stem cell proliferation and adipogenic differentiation owing to increased surface hydrophilicity. Thus, the present research show that the medical grade PLATMC based scaffolds are a potential candidate towards the development of implantable, resorbable, medical devices for adipose tissue regeneration.
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18. |
- Jain, Shubham, et al.
(author)
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Printability and Critical Insight into Polymer Properties during Direct-Extrusion Based 3D Printing of Medical Grade Polylactide and Copolyesters
- 2020
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In: Biomacromolecules. - : AMER CHEMICAL SOC. - 1525-7797 .- 1526-4602. ; 21:2, s. 388-396
-
Research review (peer-reviewed)abstract
- Various 3D printing techniques currently use degradable polymers such as aliphatic polyesters to create well-defined scaffolds. Even though degradable polymers are influenced by the printing process, and this subsequently affects the mechanical properties and degradation profile, degradation of the polymer during the process is not often considered. Degradable scaffolds are today printed and cell-material interactions evaluated without considering the fact that the polymer change while printing the scaffold. Our methodology herein was to vary the printing parameters such as temperature, pressure, and speed to define the relationship between printability, polymer microstructure, composition, degradation profile during the process, and rheological behavior. We used high molecular weight medical-grade (co)polymers, poly(L-lactide-co-epsilon-caprolactone) (PCLA), poly(L-lactide-co-glycolide) (PLGA), and poly(D,L-lactide-co-glycolide) (PDLGA), with L-lactide content ranging from 25 to 100 mol %, for printing in an extrusion-based printer (3D Bioplotter). Optical microscopy confirmed that the polymers were printable at high resolution and good speed, until a certain degree of degradation. The results show also that printability can not be claimed just by optimizing printing parameters and highlight the importance of a careful analysis of how the polymer's structure and properties vary during printing. The polymers thermally decomposed from the first processing minute and caused a decrease in the average block length of the lactide blocks in the copolymers and generated lower crystallinity. Poly(L-lactide) (PLLA) and PCLA are printable at a higher molecular weight, less degradation before printing was possible, compared to PLGA and PDLGA, a result explained by the higher complex viscosity and more elastic polymeric melt of the copolymer containing glycolide (GA) and lactide (LA). In more detail, copolymers comprised of LA and epsilon-caprolactone (CL) formed lower molecular weight compounds over the course of printing, while the PLGA copolymer was more susceptible to intermolecular transesterification reactions, which do not affect the overall molecular weight, but cause changes in the copolymer microstructure. This results in a longer printing time for PLGA than PLLA and PCLA.
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19. |
- Jain, Shubham, et al.
(author)
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Understanding of how the properties of medical grade lactide based copolymer scaffolds influence adipose tissue regeneration : Sterilization and a systematic in vitro assessment
- 2021
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In: Materials science & engineering. C, biomimetic materials, sensors and systems. - : Elsevier BV. - 0928-4931 .- 1873-0191. ; 124
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Journal article (peer-reviewed)abstract
- Aliphatic polyesters are the synthetic polymers most commonly used in the development of resorbable medical implants / devices. Various three-dimensional (3D) scaffolds have been fabricated from these polymers and used in adipose tissue engineering. However, their systematic evaluation altogether lacks, which makes it difficult to select a suitable degradable polymer to design 3D resorbable implants and / or devices able to effectively mimic the properties of adipose tissue. Additionally, the impact of sterilization methods on the medical devices, if any, must be taken into account. We evaluate and compare five different medical-grade resorbable polyesters with l-lactide content ranging from 50 to 100 mol% and exhibiting different physiochemical properties depending on the comonomer (d-lactide, ε-caprolactone, glycolide, and trimethylene carbonate). The salt-leaching technique was used to prepare 3D microporous scaffolds. A comprehensive assessment of the physical, chemical, and mechanical properties of the scaffolds was carried out in PBS at 37 ° C. The cell-material interactions and the ability of the scaffolds to promote adipogenesis of human adipose tissue-derived stem cells were assessed in vitro. The diverse physical and mechanical properties of the scaffolds, due to the different composition of the copolymers, influenced human adipose tissue-derived stem cells proliferation and differentiation. Scaffolds made from polymers which were above their glass transition temperature and with low degree of crystallinity showed better proliferation and adipogenic differentiation of stem cells. The effect of sterilization techniques (electron beam and ethylene oxide) on the polymer properties was also evaluated. Results showed that scaffolds sterilized with the ethylene oxide method better retained their physical and chemical properties. Overall, the presented research provides (i) a detailed understanding to select a degradable polymer that has relevant properties to augment adipose tissue regeneration and can be further used to fabricate medical devices / implants; (ii) directions to prefer a sterilization method that does not change polymer properties. the presented research provides (i) a detailed understanding to select a degradable polymer that has relevant properties to augment adipose tissue regeneration and can be further used to fabricate medical devices / implants; (ii) directions to prefer a sterilization method that does not change polymer properties. the presented research provides (i) a detailed understanding to select a degradable polymer that has relevant properties to augment adipose tissue regeneration and can be further used to fabricate medical devices / implants; (ii) directions to prefer a sterilization method that does not change polymer properties.
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20. |
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21. |
- Munir, Arooj, et al.
(author)
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Efficacy of copolymer scaffolds delivering human demineralised dentine matrix for bone regeneration
- 2019
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In: Journal of Tissue Engineering. - : SAGE PUBLICATIONS INC. - 2041-7314. ; 10
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Journal article (peer-reviewed)abstract
- Poly(L-lactide-co-epsilon-caprolactone) scaffolds were functionalised by 10 or 20 mu g/mL of human demineralised dentine matrix. Release kinetics up to 21 days and their osteogenic potential on human bone marrow stromal cells after 7 and 21 days were studied. A total of 390 proteins were identified by mass spectrometry. Bone regeneration proteins showed initial burst of release. Human bone marrow stromal cells were cultured on scaffolds physisorbed with 20 mu g/mL and cultured in basal medium (DDM group) or physisorbed and cultured in osteogenic medium or cultured on non-functionalised scaffolds in osteogenic medium. The human bone marrow stromal cells proliferated less in demineralised dentine matrix group and activated ERK/1/2 after both time points. Cells on DDM group showed highest expression of IL-6 and IL-8 at 7 days and expressed higher collagen type 1 alpha 2, SPP1 and bone morphogenetic protein-2 until 21 days. Extracellular protein revealed higher collagen type 1 and bone morphogenetic protein-2 at 21 days in demineralised dentine matrix group. Cells on DDM group showed signs of mineralisation. The functionalised scaffolds were able to stimulate osteogenic differentiation of human bone marrow stromal cells.
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22. |
- Rossi, Ruggero, et al.
(author)
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Photoswitches in Order : One-Pot Synthesis of Azobenzene Main-Chain and Segmented Copolymers
- 2024
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In: ACS Applied Polymer Materials. - : American Chemical Society (ACS). - 2637-6105. ; 6:2, s. 1563-1572
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Journal article (peer-reviewed)abstract
- Syntheses of multifunctional polymers aim to engineer a wide range of material properties by adjusting the composition and positioning of functional groups. While manifold syntheses of side-chain-functionalized polymers are known, synthetic protocols for main-chain-functionalized polymers are less common. This work describes a general one-pot strategy to prepare polymers containing multiple functional moieties in their main-chain, e.g., azobenzene units separated by variable oligomers. The polymerization proceeds in two steps, starting from a single azobenzene initiator and commercially available monomers (lactones and cyclic carbonates). Various main-chain-functionalized polymers were obtained with a predictable and adjustable ratio of monomer units (5-20) to photoswitchable azobenzene groups. The thermal properties of these polymers were analyzed and rationalized with regard to the parent polymers' properties and the peculiarities arising from their segmented microstructure. Furthermore, the azobenzenes' ability to undergo light-induced cis/trans-isomerization is confirmed. High isomerization yields of up to 90% were observed for the polymers in solution with a half-life of several days for the cis-isomers in solution. When irradiated as solid films, the azobenzenes still undergo isomerization, but the cis-isomers are less stable compared to the liquid state.
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23. |
- Suliman, Salwa, et al.
(author)
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Immune-instructive copolymer scaffolds using plant-derived nanoparticles to promote bone regeneration
- 2022
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In: Inflammation and Regeneration. - : Springer Nature. - 1880-8190. ; 42:1
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Journal article (peer-reviewed)abstract
- Background Age-driven immune signals cause a state of chronic low-grade inflammation and in consequence affect bone healing and cause challenges for clinicians when repairing critical-sized bone defects in elderly patients. Methods Poly(l-lactide-co-e-caprolactone) (PLCA) scaffolds are functionalized with plant-derived nanoparticles from potato, rhamnogalacturonan-I (RG-I), to investigate their ability to modulate inflammation in vitro in neutrophils and macrophages at gene and protein levels. The scaffolds' early and late host response at gene, protein and histological levels is tested in vivo in a subcutaneous rat model and their potential to promote bone regeneration in an aged rodent was tested in a critical-sized calvaria bone defect. Significant differences were tested using one-way ANOVA, followed by a multiple-comparison Tukey's test with a p value <= 0.05 considered significant. Results Gene expressions revealed PLCA scaffold functionalized with plant-derived RG-I with a relatively higher amount of galactose than arabinose (potato dearabinated (PA)) to reduce the inflammatory state stimulated by bacterial LPS in neutrophils and macrophages in vitro. LPS-stimulated neutrophils show a significantly decreased intracellular accumulation of galectin-3 in the presence of PA functionalization compared to Control (unmodified PLCA scaffolds). The in vivo gene and protein expressions revealed comparable results to in vitro. The host response is modulated towards anti-inflammatory/ healing at early and late time points at gene and protein levels. A reduced foreign body reaction and fibrous capsule formation is observed when PLCA scaffolds functionalized with PA were implanted in vivo subcutaneously. PLCA scaffolds functionalized with PA modulated the cytokine and chemokine expressions in vivo during early and late inflammatory phases. PLCA scaffolds functionalized with PA implanted in calvaria defects of aged rats downregulating pro-inflammatory gene markers while promoting osteogenic markers after 2 weeks in vivo. Conclusion We have shown that PLCA scaffolds functionalized with plant-derived RG-I with a relatively higher amount of galactose play a role in the modulation of inflammatory responses both in vitro and in vivo subcutaneously and promote the initiation of bone formation in a critical-sized bone defect of an aged rodent. Our study addresses the increasing demand in bone tissue engineering for immunomodulatory 3D scaffolds that promote osteogenesis and modulate immune responses.
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24. |
- Yassin, Mohammed A., et al.
(author)
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3D and Porous RGDC-Functionalized Polyester-Based Scaffolds as a Niche to Induce Osteogenic Differentiation of Human Bone Marrow Stem Cells
- 2019
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In: Macromolecular Bioscience. - : WILEY-V C H VERLAG GMBH. - 1616-5187 .- 1616-5195. ; 19:6
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Journal article (peer-reviewed)abstract
- Polyester-based scaffolds covalently functionalized with arginine-glycine-aspartic acid-cysteine (RGDC) peptide sequences support the proliferation and osteogenic differentiation of stem cells. The aim is to create an optimized 3D niche to sustain human bone marrow stem cell (hBMSC) viability and osteogenic commitment, without reliance on differentiation media. Scaffolds consisting of poly(lactide-co-trimethylene carbonate), poly(LA-co-TMC), and functionalized poly(lactide) copolymers with pendant thiol groups are prepared by salt-leaching technique. The availability of functional groups on scaffold surfaces allows for an easy and straightforward method to covalently attach RGDC peptide motifs without affecting the polymerization degree. The strategy enables the chemical binding of bioactive motifs on the surfaces of 3D scaffolds and avoids conventional methods that require harsh conditions. Gene and protein levels and mineral deposition indicate the osteogenic commitment of hBMSC cultured on the RGDC functionalized surfaces. The osteogenic commitment of hBMSC is enhanced on functionalized surfaces compared with nonfunctionalized surfaces and without supplementing media with osteogenic factors. Poly(LA-co-TMC) scaffolds have potential as scaffolds for osteoblast culture and bone grafts. Furthermore, these results contribute to the development of biomimetic materials and allow a deeper comprehension of the importance of RGD peptides on stem cell transition toward osteoblastic lineage.
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