Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Synthesis of degradable aliphatic polyesters: strategies to tailor the polymer microstructure
KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology. (Polymer technology)
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2018. , p. 78
Series
TRITA-CHE-Report, ISSN 1654-1081 ; 2017:35
Keyword [en]
Polymer synthesis, enzymatic synthesis, degradable polyesters, peptides, scaffolds
National Category
Polymer Technologies
Research subject
Chemical Engineering
Identifiers
URN: urn:nbn:se:kth:diva-219550ISBN: 978-91-7729-615-7 (print)OAI: oai:DiVA.org:kth-219550DiVA, id: diva2:1163588
Public defence
2018-01-15, F3, Lindstedtsvägen 26, Stockholm, 09:00 (English)
Opponent
Supervisors
Funder
Swedish Research Council, 2013-3764
Note

QC 20171207

Available from: 2017-12-07 Created: 2017-12-07 Last updated: 2017-12-07Bibliographically approved
List of papers
1. Mapping the synthesis and the impact of low molecular weight PLGA-g-PEG on sol–gel properties to design hierarchical porous scaffolds
Open this publication in new window or tab >>Mapping the synthesis and the impact of low molecular weight PLGA-g-PEG on sol–gel properties to design hierarchical porous scaffolds
2014 (English)In: Journal of polymer research, ISSN 1022-9760, E-ISSN 1572-8935, Vol. 21, no 1, p. 1-11Article in journal (Refereed) Published
Abstract [en]

Bone morphogenetic protein 2 (BMP-2)-function- alized poly(L-lactide-co-ε-caprolactone) (PLCL) porous scaf- folds have shown promising results in bone tissue regenera- tion 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 polymeri- zation and carefully characterized by nuclear magnetic reso- nance 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 deter- mined 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(ethyl- ene glycol) methyl ether) (PLGA-MPEG) appeared to con- tribute to gelation. It was possible to design a system that formed a hydrogelwithin 1min at 37 °Cwith a pHbetween 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.

Place, publisher, year, edition, pages
Springer Science+Business Media B.V., 2014
Keyword
Thermosensitive gel, PLGA-g-PEG, Porous scaffolds, Tissue engineering, Degradable polymers
National Category
Polymer Technologies
Research subject
Chemical Engineering
Identifiers
urn:nbn:se:kth:diva-219570 (URN)10.1007/s10965-013-0337-8 (DOI)000328848400001 ()2-s2.0-84890528028 (Scopus ID)
Note

QC 20171211

Available from: 2017-12-07 Created: 2017-12-07 Last updated: 2017-12-11Bibliographically approved
2. Short One-Pot Chemo-Enzymatic Synthesis of L-Lysine and L-Alanine Diblock Co-Oligopeptides
Open this publication in new window or tab >>Short One-Pot Chemo-Enzymatic Synthesis of L-Lysine and L-Alanine Diblock Co-Oligopeptides
2014 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 15, no 3, p. 735-743Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2014
Keyword
Biomedical applications, Chemo-enzymatic synthesis, Crystalline morphologies, Crystalline structure, Drug/gene delivery, H NMR spectroscopy, Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry, Self-assembling properties
National Category
Polymer Chemistry Biochemistry and Molecular Biology Organic Chemistry
Identifiers
urn:nbn:se:kth:diva-144372 (URN)10.1021/bm4015254 (DOI)000332756600005 ()2-s2.0-84896752024 (Scopus ID)
Note

QC 20140422

Available from: 2014-04-22 Created: 2014-04-22 Last updated: 2017-12-11Bibliographically approved
3. Template-assisted enzymatic synthesis of oligopeptides from a polylactide chain
Open this publication in new window or tab >>Template-assisted enzymatic synthesis of oligopeptides from a polylactide chain
Show others...
2017 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 18, no 12, p. 4271-4280Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2017
Keyword
Polymer synthesis, Polylactide, Peptide functionalization, Chemo-enzymatic synthesis
National Category
Polymer Technologies
Research subject
Chemical Engineering
Identifiers
urn:nbn:se:kth:diva-219562 (URN)10.1021/acs.biomac.7b01315 (DOI)000418109200040 ()29131581 (PubMedID)2-s2.0-85038214474 (Scopus ID)
Funder
Swedish Research Council, 2013-3764VINNOVAEU, FP7, Seventh Framework Programme, 291795
Note

QC 20171211

Available from: 2017-12-07 Created: 2017-12-07 Last updated: 2018-01-12Bibliographically approved
4. Modulating the thermal properties of poly(hydroxybutyrate) by the copolymerization of rac-beta-butyrolactone with lactide
Open this publication in new window or tab >>Modulating the thermal properties of poly(hydroxybutyrate) by the copolymerization of rac-beta-butyrolactone with lactide
2016 (English)In: New Journal of Chemistry, ISSN 1144-0546, E-ISSN 1369-9261, Vol. 40, no 9, p. 7671-7679Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2016
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:kth:diva-193865 (URN)10.1039/c6nj00298f (DOI)000382820000054 ()2-s2.0-84985041093 (Scopus ID)
Funder
VINNOVA, 291795Swedish Research Council, 621-2013-3764
Note

QC 20161012

Available from: 2016-10-12 Created: 2016-10-11 Last updated: 2017-12-11Bibliographically approved

Open Access in DiVA

The full text will be freely available from 2019-01-15 19:21
Available from 2019-01-15 19:21

Search in DiVA

By author/editor
Fagerland, Jenny
By organisation
Polymer Technology
Polymer Technologies

Search outside of DiVA

GoogleGoogle Scholar

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 144 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf