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Tuning the release rate of acidic degradation products through macromolecular design of caprolactone-based copolymers
KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi.ORCID-id: 0000-0002-7790-8987
KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi.
KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi.ORCID-id: 0000-0002-5850-8873
KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi.ORCID-id: 0000-0001-8696-9143
2007 (engelsk)Inngår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 129, nr 19, s. 6308-6312Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Macromolecular engineering is presented as a tool to control the degradation rate and release rate of acidic degradation products from biomedical polyester ethers. Three different caprolactone/1,5-dioxepan-2-one (CL/DXO) copolymers were synthesized: DXO/CL/DXO triblock, CL/DXO multiblock, and random cross-linked CL/DXO copolymer. The relation of CL and DXO units in all three copolymers was 60/40 mol %. The polymer discs were immersed in phosphate buffer solution at pH 7.4 and 37 degrees C for up to 364 days. After different time periods degradation products were extracted from the buffer solution and analyzed. In addition mass loss, water absorption, molecular weight changes, and changes in thermal properties were determined. The results show that the release rate of acidic degradation products, a possible cause of acidic microclimates and inflammatory responses, is controllable through macromolecular design, i.e., different distribution of the weak linkages in the copolymers.

sted, utgiver, år, opplag, sider
2007. Vol. 129, nr 19, s. 6308-6312
Emneord [en]
epsilon-caprolactone, aliphatic polyesters, hydrolytic degradation, l-lactide, 1, 5-dioxepan-2-one, polymers, implants, polymerization, glycolide, blends
HSV kategori
Identifikatorer
URN: urn:nbn:se:kth:diva-16623DOI: 10.1021/ja0702871ISI: 000246415100047Scopus ID: 2-s2.0-34249041978OAI: oai:DiVA.org:kth-16623DiVA, id: diva2:334665
Merknad

QC 20150720

Tilgjengelig fra: 2010-08-05 Laget: 2010-08-05 Sist oppdatert: 2020-01-08bibliografisk kontrollert
Inngår i avhandling
1. Controlled Degradation of Polyester-Ethers Revealed by Mass Spectrometry Techniques
Åpne denne publikasjonen i ny fane eller vindu >>Controlled Degradation of Polyester-Ethers Revealed by Mass Spectrometry Techniques
2008 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

The use of degradable biomedical materials in e.g. tissue engineering and controlled drug delivery has changed medical science during recent decades. The key question is to adapt the material with respect to mechanical properties, surface characteristics, and degradation profile to suit its intended application. Products formed during the degradation of bioresorbable materials are generally considered non-toxic and they are excreted from the human body. However, large amounts of specific degradation products such as hydroxyacids and oligomers may induce a pH decrease and a subsequent inflammatory response at the implantation site.

 

In this study, macromolecular design and a combination of cross-linking and adjusted hydrophilicity are utilized as tools to control and tailor the degradation rate and the subsequent release of degradation products from polyester-ethers. A series of different homo- and copolymers of e-caprolactone (CL) and 1,5-dioxepan-2-one (DXO) were synthesized and their hydrolytic degradation was monitored in aqueous media at 37 °C for up to 546 days. The low and medium molar mass degradation products released during hydrolysis were monitored by various mass spectrometry techniques. The materials studied included linear DXO/CL triblock and multiblock copolymers, PCL and PDXO linear homopolymers, and cross-linked homo- and random copolymers of CL/DXO where 2,2’-bis-(ε-caprolactone-4-yl) propane (BCP) was used as a cross-linking agent.

 

The results show that macromolecular engineering and controlled hydrophilicity of cross-linked networks are useful tools for customizing the release rate of acidic degradation products. Thereby, the formation of local acidic environments is prevented and the risk of inflammatory responses in the body is reduced.

Abstract [sv]

Läkarvetenskapen har under de senaste årtiondena förändrats genom användandet av nedbrytbara biomedicinska material inom t.ex. vävnadsersättning och kontrollerad läkemedelsfrisättning. Nyckeln är att anpassa materialets mekaniska egenskaper, ytegenskaper och nedbrytningsprofil för den tilltänkta tillämpningen. Produkterna som bildas under nedbrytningen av bioresorberbara material anses generellt vara icke-toxiska och utsöndras ur människokroppen, men stora mängder specifika nedbrytningsprodukter som t.ex. hydroxysyror kan orsaka en pH-sänkning och därmed en inflammatorisk reaktion vid implantationsplatsen.

 

I detta arbete används makromolekylär design och en kombination av tvärbindning och anpassad hydrofilicitet som verktyg för att kontrollera och skräddarsy nedbrytningshastigheten och den efterföljande frisättningen av nedbrytningsprodukter från polyester-etrar. En serie av olika homo- och sampolymerer av e-kaprolakton (CL) och 1,5-dioxepan-2-on (DXO) syntetiserades och deras hydrolytiska nedbrytning studerades i vattenlösning vid 37 °C i upp till 546 dagar. De låg- och medelmolekylära nedbrytningsprodukterna som frisattes under hydrolysen analyserades med olika masspektrometritekniker. Materialen som undersöktes inkluderade linjära DXO/CL triblock- och multiblocksampolymerer, linjära PCL och PDXO homopolymerer, samt tvärbundna homo- och slumpvisa sampolymerer av CL och DXO där 2,2’-bis(e-kaprolakton-4-yl)propan (BCP) användes som tvärbindare.

 

Resultaten visar att makromolekylär design och tvärbundna nätverk med kontrollerad hydrofilicitet är användbara verktyg för att skräddarsy frisättningshastigheten av sura nedbrytningsprodukter. Därmed kan bildandet av lokalt sura miljöer förhindras och risken för inflammatoriska reaktioner i kroppen minskas.

 

sted, utgiver, år, opplag, sider
Stockholm: KTH, 2008. s. 59
Serie
Trita-CHE-Report, ISSN 1654-1081 ; 2008:57
Emneord
Degradation products, biocompatibility, -caprolactone, 1, 5-dioxepan-2-one, 6-hydroxyhexanoic acid, 3-(2-hydroxyethoxy)propanoic acid, oligomers
HSV kategori
Identifikatorer
urn:nbn:se:kth:diva-4898 (URN)978-91-7415-098-8 (ISBN)
Disputas
2008-09-26, F3, KTH, Lindstedtsvägen 26, Stockholm, 10:00 (engelsk)
Opponent
Veileder
Merknad
QC 20100812Tilgjengelig fra: 2008-09-17 Laget: 2008-09-17 Sist oppdatert: 2010-08-12bibliografisk kontrollert
2. Macromolecular design and architecture of aliphatic polyesters
Åpne denne publikasjonen i ny fane eller vindu >>Macromolecular design and architecture of aliphatic polyesters
2008 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Public health care has reached a level where tissue or organ reconstruction by means of biodegradable short-term implants via e.g. tissue engineering will be practicable in the near future. The vital issue now is to be able to reproducibly fabricate and design new materials with the appropriate properties and three-dimensional shape, and to facilitate their sterilization. In this thesis, macromolecular design and polymer architecture techniques are used to synthesize well-defined polymers with narrow molecular weight distributions (MWD), and to control the reactions upon sterilization, and the degradation rate and profile.

A model system for the ring-opening polymerization of L-lactide (LLA) initiated by a spirocyclic tin initiator was developed to synthesize star-shaped polymers. It was shown that an increase in temperature and a decrease in the dielectrical constant of the solvents increased the reaction rate. The versatility of the spirocyclic tin initiator system was subsequently established, by homopolymerization of ε-caprolactone (CL) and 1,5-dioxepan-2-one (DXO) and this system was compared with a conventional system using stannous octoate (Sn(Oct)2) and pentaerythritol ethoxylate. Two different strategies were assessed for the two initiator systems for the synthesis of copolymers that are random or blocky in their nature. Random copolymers with distinct sequence lengths were synthesized using both initiator systems, together with block poly(DXO-co-LLA) and poly(CL-co-LLA) with narrow MWD.

Three different types of copolymers of LLA, CL and DXO were synthesized using Sn(Oct)2 and ethylene glycol. A solvent casting and particulate leaching technique was developed and applied to construct porous scaffolds of the copolymers. The porous scaffolds were subsequently sterilized using electron beam or γ-irradiation and it was shown that the reactions induced by radiation can be used to tailor the end-properties of the materials.

Homo- and copolymers of CL and DXO with different macromolecular designs (triblock and multiblock) and different polymer architectures (linear and cross-linked) were synthesized and degraded in a phosphate buffer solution for up to 364 days. By altering the network composition, the release pattern of acidic degradation products was controlled, where an increase in DXO content led to an increase in the release of both monomeric hydroxy-acids. Varying the distribution of the more hydrolysis-susceptible DXO-sequences in the linear copolymers also enabled the amount of monomeric hydroxy acids released to be controlled, where the triblock copolymer showed the highest release.

sted, utgiver, år, opplag, sider
Stockholm: KTH, 2008. s. 62
Serie
Trita-CHE-Report, ISSN 1654-1081 ; 2008:11
Emneord
Ring-opening polymerization, L-lactide, 1, 5-dioxepane-2-one, ε-caprolactone, Polymerization kinetics, Star-shaped architecture, Spirocyclic tin initiator
HSV kategori
Identifikatorer
urn:nbn:se:kth:diva-4657 (URN)978-91-7178-883-2 (ISBN)
Disputas
2008-03-20, F3, KTH, Lindstedtsvägen 26, Stockholm, 09:00
Opponent
Veileder
Merknad
QC 20100901Tilgjengelig fra: 2008-03-03 Laget: 2008-03-03 Sist oppdatert: 2010-09-01bibliografisk kontrollert
3. Controllable degradation product migration from biomedical polyester-ethers
Åpne denne publikasjonen i ny fane eller vindu >>Controllable degradation product migration from biomedical polyester-ethers
2007 (engelsk)Licentiatavhandling, med artikler (Annet vitenskapelig)
Abstract [en]

The use of degradable biomedical materials has during the past decades indeed modernized medical science, finding applications in e.g. tissue engineering and drug delivery. The key question is to adapt the material with respect to mechanical properties, surface characteristics and degradation profile to suit the specific application. Degradation products are generally considered non-toxic and they are excreted from the human body. However, large amounts of hydroxy acids may induce a pH decrease and a subsequent inflammatory response at the implantation site.

In this study, macromolecular design and a combination of cross-linking and adjusted hydrophilicity are utilized as tools to control and tailor degradation rate and subsequent release of degradation products from biomedical polyester-ethers. A series of different homo- and copolymers of -caprolactone (CL) and 1,5-dioxepan-2-one (DXO) were synthesized and their hydrolytic degradation was monitored in phosphate buffer solution at pH 7.4 and 37 °C for up to 546 days. The various materials comprised linear DXO/CL triblock and multiblock copolymers, PCL linear homopolymer and porous structure, and random cross-linked homo- and copolymers of CL/DXO using 2,2’-bis-(ε-caprolactone-4-yl) propane (BCP) as a cross-linking agent.

The results showed that macromolecular engineering and controlled hydrophilicity of cross-linked networks were useful implements for customizing the release rate of acidic degradation products in order to prevent the formation of local acidic environments and thereby reduce the risk of inflammatory responses in the body.

sted, utgiver, år, opplag, sider
Stockholm: KTH, 2007. s. 39
Serie
Trita-CHE-Report, ISSN 1654-1081 ; 2007:23
Emneord
degradation products, ε-caprolactone, 1, 5-dioxepan-2-one, 6-hydroxyhexanoic acid, 3-(2-hydroxyethoxy)propanoic acid, cross-linking, inflammatory response
HSV kategori
Identifikatorer
urn:nbn:se:kth:diva-4366 (URN)978-91-7178-653-1 (ISBN)
Presentation
2007-05-24, E3, KTH, Osquars backe 14, Stockholm, 09:00
Opponent
Veileder
Merknad
QC 20101109Tilgjengelig fra: 2007-05-10 Laget: 2007-05-10 Sist oppdatert: 2020-01-08bibliografisk kontrollert

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