| 1. |
- Fagerland, Jenny, et al.
(författare)
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Mapping the synthesis and the impact of low molecular weight PLGA-g-PEG on sol-gel properties to design hierarchical porous scaffolds
- 2013
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Ingår i: Journal of polymer research. - : Springer Science and Business Media LLC. - 1022-9760 .- 1572-8935. ; 21:1, s. 337-
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Tidskriftsartikel (refereegranskat)abstract
- Bone morphogenetic protein 2 (BMP-2)-functionalized poly(l-lactide-co-epsilon-caprolactone) (PLCL) porous scaffolds have shown promising results in bone tissue regeneration studies. It is believed that even better results are achieved by hierarchical porous scaffolds and a designed sequential release of growth factors. We therefore synthesized (l-lactide-co-glycolide)-g-poly(ethylene glycol) (PLGA-g-PEG) oligomers which could be injected into PLCL porous scaffolds. They were synthesized by ring-opening polymerization and carefully characterized by nuclear magnetic resonance spectroscopy (NMR), matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), and size exclusion chromatography (SEC). The sol-gel transition temperature, pH, and functional life were determined and correlated with the molecular structure of PLGA-g-PEG. We found that low molecular weight PLGA-g-PEG was obtained and poly(l-lactide-co-glycolide-co-poly(ethylene glycol) methyl ether) (PLGA-MPEG) appeared to contribute to gelation. It was possible to design a system that formed a hydrogel within 1 min at 37 A degrees C with a pH between 6 and 7 and with a functional life of around 1 month. These low molecular weight thermosensitive PLGA-g-PEG oligomers, which can be injected into PLCL scaffolds, appear promising for bone tissue engineering applications.
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| 2. |
- Fagerland, Jenny, et al.
(författare)
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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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Ingår i: New Journal of Chemistry. - : Royal Society of Chemistry. - 1144-0546 .- 1369-9261. ; 40:9, s. 7671-7679
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Fagerland, Jenny, et al.
(författare)
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Short One-Pot Chemo-Enzymatic Synthesis of L-Lysine and L-Alanine Diblock Co-Oligopeptides
- 2014
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 15:3, s. 735-743
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Tidskriftsartikel (refereegranskat)abstract
- Amphiphilic diblock co-oligopeptides are interesting and functional macromolecular materials for biomedical applications because of their self-assembling properties. Here, we developed a synthesis method for diblock co-oligopeptides by using chemo-enzymatic polymerization, which was a relatively short (30 min) and efficient reaction (over 40% yield). Block and random oligo(L-lysine-co-L-alanine) [oligo(Lys-co-Ala)] were synthesized using activated papain as enzymatic catalyst. The reaction time was optimized according to kinetic studies of oligo(L-alanine) and oligo(L-lysine). Using H-1 NMR spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we confirmed that diblock and random co-oligopeptides were synthesized. Optical microscopy further revealed differences in the crystalline morphology between random and block co-oligopeptides. Plate-like, hexagonal, and hollow crystals were formed due to the strong impact of the monomer distribution and pH of the solution. The different crystalline structures open up interesting possibilities to form materials for both tissue engineering and controlled drug/gene delivery systems.
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| 4. |
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| 5. |
- Fagerland, Jenny, 1985-
(författare)
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Synthesis and Characterization of Self-Assembling Low Molecular Weight Copolymers for Bioengineering Applications
- 2013
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The constant need for improved biomedical materials and the interest in producing materials with similar properties to the extracellular matrix in different tissues has resulted in increasing interest in research on hydrogels. Over the last decade self-assembling copolymers have been of particular interest since they form hydrogels in response to external stimuli such as temperature. In this thesis, two self-assembling low molecular weight copolymers; poly(L-lactide-co-glycolide) grafted with poly(ethylene glycol) methyl ether (PLGA-g-MPEG) and poly(L-lysine-co-L-alanine) (poly(Lys-co-Ala)) were synthesized for possible bioengineering applications. Their chemical structure and composition was analysed by nuclear magnetic resonance spectroscopy (NMR) and matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The results showed that low molecular weight PLGA-g-MPEG and poly(Lys-co-Ala) were successfully obtained.PLGA-g-MPEG hydrogels were formed at 37°C, within 1 minute, at a pH between 6-7 and had a functional life of one month. The block cooligopeptides of L-lysine and L-alanine formed cubic, hexagonal and hollow crystals in low pH and irregularly shaped crystals in at pH 7, while plate-like crystals were formed at both pH 3 and 7 form the random cooligopeptides. Evaluation of the properties of the low molecular weight copolymers, such as pH, functional life and crystalline morphology, revealed that the chemical composition and solvent composition strongly affects their self-assembling properties.These synthesized low molecular weight copolymers showed promise results for use as material in biomedical applications. Areas of potential use for these materials include bioengineered hierarchical scaffold material facilitating sequential release of growth factors, for example in bone tissue engineering, and as materials for encapsulated drug delivery.
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| 6. |
- Fagerland, Jenny, 1985-
(författare)
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Synthesis of degradable aliphatic polyesters: strategies to tailor the polymer microstructure
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 7. |
- Fagerland, Jenny, 1985-, et al.
(författare)
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Template-assisted enzymatic synthesis of oligopeptides from a polylactide chain
- 2017
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 18:12, s. 4271-4280
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Nielsen, Rasmus Oestergaard, et al.
(författare)
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Statement on methods in sport injury research from the 1st METHODS MATTER Meeting, Copenhagen, 2019
- 2020
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Ingår i: British Journal of Sports Medicine. - : BMJ PUBLISHING GROUP. - 0306-3674 .- 1473-0480. ; 54:15, s. 941-947
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Forskningsöversikt (refereegranskat)abstract
- High quality sports injury research can facilitate sports injury prevention and treatment. There is scope to improve how our field applies best practice methods-methods matter (greatly!). The 1st METHODS MATTER Meeting, held in January 2019 in Copenhagen, Denmark, was the forum for an international group of researchers with expertise in research methods to discuss sports injury methods. We discussed important epidemiological and statistical topics within the field of sports injury research. With this opinion document, we provide the main take-home messages that emerged from the meeting.
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| 9. |
- Nielsen, Rasmus Ostergaard, et al.
(författare)
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Statement on Methods in Sport Injury Research From the First METHODS MATTER Meeting, Copenhagen, 2019
- 2020
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Ingår i: Journal of Orthopaedic and Sports Physical Therapy. - : J O S P T. - 0190-6011 .- 1938-1344. ; 50:5, s. 226-233
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- SYNOPSIS: High-quality sports injury research can facilitate sports injury prevention and treatment. There is scope to improve how our field applies best-practice methods-methods matter (greatly!). The first METHODS MATTER meeting, held in January 2019 in Copenhagen, Denmark, was the forum for an international group of researchers with expertise in research methods to discuss sports injury methods. We discussed important epidemiological and statistical topics within the field of sports injury research. With this opinion document, we provide the main take-home messages that emerged from the meeting. Meeting participants agreed that the definition of sport injury depends on the research question and context. It was considered essential to be explicit about the goal of the research effort and to use frameworks to illustrate the assumptions that underpin measurement and the analytical strategy. Complex systems were discussed to illustrate how potential risk factors can interact in a nonlinear way. This approach is often a useful alternative to identifying single risk factors. Investigating changes in exposure status over time is important when analyzing sport injury etiology, and analyzing recurrent injury, subsequent injury, or injury exacerbation remains challenging. The choice of statistical model should consider the research question, injury measure (eg, prevalence, incidence), type and granularity of injury data (categorical or continuous), and study design. Multidisciplinary collaboration will be a cornerstone for future high-quality sport injury research. Working outside professional silos in a diverse, multidisciplinary team benefits the research process, from the formulation of research questions and designs to the statistical analyses and dissemination of study results in implementation contexts. This article has been copublished in the British Journal of Sports Medicine and the Journal of Orthopaedic & Sports Physical Therapy.
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