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Macromolecular synthesis of functional degradable aliphatic polyesters and porous scaffold design
KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

There is an increasing demand for new materials in biomedical applications with material properties that are highly specific for each application area. The search for new materials requires the creation of materials with suitable mechanical properties, functionalities, three-dimensional structures and a controlled degradation profile. The focus of the work described in this thesis has been on the synthesis of functional degradable aliphatic polyesters, on the design of porous scaffolds and on their synthesis with bio-safe catalyst/initiator systems.  

An unsaturated aliphatic polyester has been synthesized by condensation polymerization to produce poly(but-2-ene-1,4-diyl malonate) (PBM), which was applicable as a cross-linked network and as a macro-co-initiator for the ring-opening polymerization (ROP) of cyclic ester monomers. The method of preparation of PBM was simple and straightforward and there was no need to purify the monomers or add a catalyst. PBM was successfully cross-linked with UV-radiation to form a transparent, colorless, flexible and strong film. When PBM was used as a macro-co-initiator, a triblock copolymer was formed with PBM middle blocks and poly(L-lactide) (PLLA) or poly(ε-caprolactone) side blocks. The ductility of the triblock copolymer of PLLA was greatly enhanced and the strength was maintained compared to the polymer obtained when PLLA was polymerized with ethylene glycol as co-initiator. The triblock copolymers were easily cross-linked to give materials with greater strength and higher modulus as a result. When these polymers were subjected to hydrolysis, a rapid initial hydrolysis of the amorphous PBM middle block changed the microstructure from triblock to diblock, with a significant reduction in ductility and number average molecular weight. Highly porous scaffolds were created from these functional materials and the mechanical properties were evaluated by a cyclic compression test under mimicked physiological conditions.

Copolymers of L-lactide (LLA) and ε-caprolactone (CL), trimethylene carbonate (TMC) or 1,5-dioxepane-2-one (DXO) have been synthesized with a low stannous-2-ethyl hexanoate  (Sn(Oct)2) ratio and used to fabricate porous tubular scaffolds. The tubes were designed to have a range of mechanical properties suitable for nerve regeneration, with different porosities and different numbers of layers in the tube wall. The adaptability of an immersion-coating and porogen-leaching technique was demonstrated by creating tubes with different dimensions.

Although a low amount of residual tin (monomer-to-initiator ratio of 10000:1) is accepted in biomedical applications, an efficient bio-safe catalyst/initiator system would be favored. The catalytic activities of bio-safe Bi (III) acetate and creatinine towards the ROP of LLA have been compared with those of Sn(Oct)2-based systems and with those of a system catalyzed by enzymes. All these systems were shown to be suitable catalysts for the synthesis of high and moderate molecular weight PLLAs.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology , 2011. , 75 p.
Series
Trita-CHE-Report, ISSN 1654-1081 ; 2011:45
Keyword [en]
functional polyesters, condensation polymerization, L-lactide, ε-caprolactone, triblock copolymer, mechanical properties, porous scaffolds, tissue engineering, ring-opening polymerization, Bi(III) acetate, creatinine, stannous 2-ethylhexanoate, enzyme, degradation products
National Category
Polymer Chemistry
Identifiers
URN: urn:nbn:se:kth:diva-38583ISBN: 978-91-7501-060-1 (print)OAI: oai:DiVA.org:kth-38583DiVA: diva2:437353
Public defence
2011-09-22, F3, Lindstedtsvägen 26, KTH, Stockholm, 13:00 (English)
Opponent
Supervisors
Note
QC 20110901Available from: 2011-08-30 Created: 2011-08-29 Last updated: 2011-09-01Bibliographically approved
List of papers
1. Design of Elastomeric Homo- and Copolymer Networks of Functional Aliphatic Polyester for Use in Biomedical Applications
Open this publication in new window or tab >>Design of Elastomeric Homo- and Copolymer Networks of Functional Aliphatic Polyester for Use in Biomedical Applications
2010 (English)In: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002, Vol. 22, no 9, 3009-3014 p.Article in journal (Refereed) Published
Abstract [en]

An unsaturated aliphatic polyester was synthesized by condensation polymerization to yield the pre-polymer, poly(but-2-ene-1,4-diyl malonate) (PBM), which is applicable as an elastomeric network and as a macroinitiator for the polymerization of cyclic ester monomers. The method of preparation was simple and straightforward with no need to purify the monomers or add a potentially harmful catalyst. The number average molecular weight of the pre-polymer could easily be increased from 5000 to 12000 by extending the reaction time. The pre-polymer PBM was successfully cross-linked with UV-radiation to form a clear, transparent, colorless, flexible, and strong film. PBM as a macroinitiator for L-lactide (LLA) and epsilon-caprolactone (CL) polymerizations highly increased the ductility of the LLA-polymer, while maintaining the strength, compared to PLLA polymerized with common initiators. The tensile properties of PCL were also improved. The linear PCL-PBM and PLLA-PBM polymers were easily cross-linked to give polymers with greater strength and higher modulus as the result.

Keyword
epsilon-caprolactone, cross-linking, enzymatic polymerization, poly(propylene fumarate), l-lactide, 1, 5-dioxepan-2-one, polymers, initiator, kinetics
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:kth:diva-19409 (URN)10.1021/cm100520j (DOI)000277194600042 ()2-s2.0-77951964678 (Scopus ID)
Funder
Swedish Research Council, 2008-5538
Note
QC 20100525Available from: 2010-08-05 Created: 2010-08-05 Last updated: 2017-12-12Bibliographically approved
2. Macromolecular Design of Aliphatic Polyesters with Maintained Mechanical Properties and a Rapid, Customized Degradation Profile
Open this publication in new window or tab >>Macromolecular Design of Aliphatic Polyesters with Maintained Mechanical Properties and a Rapid, Customized Degradation Profile
2011 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 12, no 6, 2382-2388 p.Article in journal (Refereed) Published
Abstract [en]

An innovative type of triblock copolymer that maintains and even increases the mechanical properties of poly(L-lactide) (PLLA) and poly(epsilon-caprolactone) (PCL) with a controlled, predictable, and rapid degradation profile has been synthesized. Elastic triblock copolymers were formed from the hydrophobic and crystalline PLLA and PCL with an amorphous and hydrophilic middle block of poly(but-2-ene-1,4-diyl malonate) (PBM). The polymers were subjected to degradation in PBS at 37 degrees C for up to 91 days. Prior to degradation, ductility of the PLLA-PBM-PLLA was approximately 4 times greater than that of the homopolymer of PLLA, whereas the modulus and tensile stress at break were unchanged. A rapid initial hydrolysis in the amorphous PBM middle block changed the microstructure from triblock to diblock with a significant reduction in ductility and molecular weight. The macromolecular structure of the triblock copolymer of PLLA and PBM generates a more flexible and easier material to handle during implant, with the advantage of a customized degradation profile, demonstrating its potential use in future biomedical applications.

Keyword
RING-OPENING POLYMERIZATION, EPSILON-CAPROLACTONE, L-LACTIDE, TRIMETHYLENE CARBONATE, HYDROLYTIC DEGRADATION, MULTIBLOCK COPOLYMERS, TRIBLOCK COPOLYMERS, BLOCK-COPOLYMERS, 1, 5-DIOXEPAN-2-ONE, POLYLACTONES
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-35634 (URN)10.1021/bm2004675 (DOI)000291499900051 ()2-s2.0-79958840855 (Scopus ID)
Funder
Swedish Research Council, 2008-5538EU, European Research Council, 246776
Note
QC 20110704Available from: 2011-07-04 Created: 2011-07-04 Last updated: 2017-12-11Bibliographically approved
3. Assessing the Degradation Profile of Functional Aliphatic Polyesters with Precise Control of the Degradation Products
Open this publication in new window or tab >>Assessing the Degradation Profile of Functional Aliphatic Polyesters with Precise Control of the Degradation Products
2012 (English)In: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 12, no 2, 260-268 p.Article in journal (Refereed) Published
Abstract [en]

The pre-polymer poly(but-2-ene-1,4-diyl malonate) (PBM) and a series of PBM-based materials are shown to be degradable under physiological conditions in vitro and they are therefore presented as potential materials for biomedical applications. Four different PBM-based materials are synthesized: a PBM homopolymer, crosslinked PBM with and without spacer, and a triblock copolymer of PBM and PLLA with the PBM as an amorphous middle block. The polymers are subjected to hydrolytic degradation in phosphate-buffered saline at pH = 7.4 and 37 °C. The results show that all the PBM-based materials degrade without a rapid release of acidic degradation products or any substantial lowering of the pH that might jeopardize their biocompatibility.

Keyword
biocompatibility, degradation products, polyesters
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:kth:diva-38610 (URN)10.1002/mabi.201100288 (DOI)000299825500012 ()22095708 (PubMedID)2-s2.0-84856583645 (Scopus ID)
Funder
Swedish Research Council, 2008-5538
Available from: 2011-08-30 Created: 2011-08-30 Last updated: 2017-12-08Bibliographically approved
4. Functional and highly porous scaffolds for biomedical applications
Open this publication in new window or tab >>Functional and highly porous scaffolds for biomedical applications
Show others...
2011 (English)In: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 11, no 10, 1432-1442 p.Article in journal (Refereed) Published
Abstract [en]

Highly porous functional scaffolds were obtained from linear and cross-linked multifunctional poly(ε-caprolactone) and poly(L-lactide). The polymers were synthesized by ring-opening polymerization of ε-caprolactone and L-lactide using poly(but-2-ene-1,4-diyl malonate) (PBM) as macroinitiator and stannous 2-ethylhexanoate. The presence of a double bond in each repeating unit of PBM enabled cross-linking of both scaffolds and films. Soft and flexible scaffolds were created from cross-linked PBM. The mechanical properties of scaffolds and films were evaluated under cyclic conditions, with a focus on the compositions and molecular weights. It was obvious that PBM in the polymers and its cross-linking ability resulted in tunable material characteristics, including an increased ability to recover after repeated loading.

Keyword
functionalization of polymers, porous scaffolds, ring-opening polymerization, tissue engineering
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:kth:diva-34173 (URN)10.1002/mabi.201100166 (DOI)000296138500016 ()2-s2.0-80053929414 (Scopus ID)
Funder
Swedish Research Council, 2008-5538
Available from: 2011-05-27 Created: 2011-05-27 Last updated: 2017-12-11Bibliographically approved
5. Design of Resorbable Porous Tubular Copolyester Scaffolds for Use in Nerve Regeneration
Open this publication in new window or tab >>Design of Resorbable Porous Tubular Copolyester Scaffolds for Use in Nerve Regeneration
2009 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 10, no 5, 1259-1264 p.Article in journal (Refereed) Published
Abstract [en]

Copolymers of L,L-lactide (LLA), epsilon-caprolactone (CL), trimethylene carbonate (TMC), or 1,5-dioxepane-2-one (DXO) were used to design porous tubular scaffolds with various mechanical properties, porosities, and numbers of layers in the tube wall. The mechanical properties of the tubular scaffold types showed good suitability for nerve regeneration and other nonload-bearing tissue engineering applications and were easy to handle without damaging the porous structure. A low stannous 2-ethylhexanoate-to-monomer ratio of 1:10000 did not change the tensile properties of the copolymer tubes significantly compared to those of scaffolds made using a Sn(Oct)(2)-to-monomer ratio of 1:600. The adaptability of the immersion coating and porogen leaching technique was demonstrated by creating tubes with different designs. Tubes with different wall layers were created by varying the immersion solutions, and the ease of altering the porosity, pore shape, and pore size was exemplified by using sodium chloride alone or mixed with poly(ethylene glycol) as porogen.

Keyword
l-lactide; epsilon-caprolactone; trimethylene carbonate; aliphatic polyesters; molecular-weight; cyclic dimer; copolymers; 1, 5-dioxepan-2-one; polymerization; guide
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:kth:diva-14415 (URN)10.1021/bm900093r (DOI)000265914200031 ()2-s2.0-66149089558 (Scopus ID)
Note
QC 20100805Available from: 2010-08-05 Created: 2010-08-05 Last updated: 2017-12-12Bibliographically approved
6. Bio-Safe Synthesis of Linear and Branched PLLA
Open this publication in new window or tab >>Bio-Safe Synthesis of Linear and Branched PLLA
2010 (English)In: Journal of Polymer Science Part A: Polymer Chemistry, ISSN 0887-624X, E-ISSN 1099-0518, Vol. 48, no 5, 1214-1219 p.Article in journal (Refereed) Published
Abstract [en]

The catalytic activities of Bi(III) acetate (Bi(OAc)(3)) and of creatinine towards the ring-opening polymerization of L-lactide have been compared with those of a stannous (II) ethylhexanoate ((SnOct)(2))-based system and with those of a system catalyzed by enzymes. All four were suitable catalysts for the synthesis of high and moderate molecular weight poly(L-lactide)s and the differences in reactivity and efficiency have been studied. Linear and branched poly(L-lactide)s were synthesized using these bio-safe initiators together with ethylene glycol, pentaerythritol, and myoinositol as coinitiators. The polymerizations were performed in bulk at 120 and 140 degrees C and different reactivities and molecular weights were achieved by adding different amounts of coinitiators. A molecular weight of 105,900 g/mol was achieved with 99% conversion in 5 h at 120 degrees C with a Bi(OAc)(3)-based system. This system was comparable to Sn(Oct)(2) at 140 degrees C. The reactivity of creatinine is lower than that of Bi(OAc)(3) but higher compared with enzymes lipase PS (Pseudomonas fluorescens). A ratio of Sn(Oct)(2) M-o/I-o 10,000:1 was needed to achieve a polymer with a reasonable low amount of tin residue in the precipitated polymer, and a system catalyzed by creatinine at 140 degrees C has a higher conversion rate than such a system.

Keyword
Bi(III) acetate, creatinine, initiator, polyester, ring-opening, polymerization, tin 2-ethylhexanoate, ring-opening polymerization, l-lactide, epsilon-caprolactone, porous, scaffolds, in-vitro, initiators, copolymers, bismuth, poly(epsilon-caprolactone), polylactones
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:kth:diva-19255 (URN)10.1002/pola.23884 (DOI)000274942000024 ()2-s2.0-76249099182 (Scopus ID)
Funder
Swedish Research Council, 2008-5538
Note
QC 20100525Available from: 2010-08-05 Created: 2010-08-05 Last updated: 2017-12-12Bibliographically approved
7. The environmental influence in enzymatic polymerization of aliphatic polyesters in bulk and aqueous mini-emulsion
Open this publication in new window or tab >>The environmental influence in enzymatic polymerization of aliphatic polyesters in bulk and aqueous mini-emulsion
2010 (English)In: Polymer, ISSN 0032-3861, E-ISSN 1873-2291, Vol. 51, no 23, 5318-5322 p.Article in journal (Refereed) Published
Abstract [en]

The catalytic effect of enzymes in different environments has been compared. Biodegradable polyesters and corresponding nanoparticles have been synthesized by an "eco-friendly" technique; enzyme-catalyzed ring-opening polymerization of lactones in bulk and in an aqueous mini-emulsion. Lipases from Burkholderia cepacia (lipase PS), B. cepacia immobilized on ceramic, Pseudomonas fluorescens and Candida Antarctica have been used as catalysts in the polymerization of L-Lactide (LLA), pentadecanolide (PDL) and hexadecanolide (HDL). The reaction conditions during the bulk polymerization of LLA were varied by adding different amounts of ethylene glycol at 100 degrees C or 125 degrees C. A number average molecular weight (M-n) of 78,100 was obtained when lipase PS was used at 125 degrees C. Lipase PS had a high catalytic activity in an aqueous environment with 100% conversion in 4 h, and the nanoparticles obtained from mini-emulsion polymerization were between 113 and 534 nm in size. The amount of hydrophobe affected the size of the PDL nanoparticles produced, less than the amount of surfactant in both systems.

Keyword
Enzyme, Ring-opening polymerization, Mini-emulsion
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:kth:diva-27052 (URN)10.1016/j.polymer.2010.09.016 (DOI)000284029200006 ()2-s2.0-77958161284 (Scopus ID)
Note
QC 20101213Available from: 2010-12-13 Created: 2010-12-06 Last updated: 2017-12-11Bibliographically approved

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