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Poly(epsilon-caprolactone-co-p-dioxanone): a Degradable and Printable Copolymer for Pliable 3D Scaffolds Fabrication toward Adipose Tissue Regeneration
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.ORCID iD: 0000-0001-7135-9158
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.ORCID iD: 0000-0002-6877-7858
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
Univ Bergen, Fac Med, Dept Clin Dent, N-5020 Bergen, Norway..
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2020 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 21, no 1, p. 188-198Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC , 2020. Vol. 21, no 1, p. 188-198
National Category
Polymer Chemistry
Identifiers
URN: urn:nbn:se:kth:diva-267517DOI: 10.1021/acs.biomac.9b01126ISI: 000507429500017PubMedID: 31549825Scopus ID: 2-s2.0-85073161599OAI: oai:DiVA.org:kth-267517DiVA, id: diva2:1422927
Note

QC 20200409

Available from: 2020-04-09 Created: 2020-04-09 Last updated: 2022-06-26Bibliographically approved
In thesis
1. Degradable copolymers in additive manufacturing: controlled fabrication of pliable scaffolds
Open this publication in new window or tab >>Degradable copolymers in additive manufacturing: controlled fabrication of pliable scaffolds
2021 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [sv]

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.

Abstract [en]

In tissue engineering, the production of well-defined scaffolds with a porous architecture from degradable polymers is of great interest. Detailed designs have become feasible through the development of additive manufacturing. A small nozzle size is needed to obtain detailed scaffold structures, and careful control of the rheological properties is therefore required during production. A lower viscosity of the melt allows for easier printability, but a high molar mass is required to produce scaffolds that can retain mechanical properties over the time needed for tissue regeneration. An additional challenge of using degradable polymers with high molar mass in any melt-based processing is that thermal degradation can reduce the molar mass during the production stage. To utilise medical grade degradable polymers whilst limiting the thermal degradation a rheological analysis of the most commonly used commercial medical-grade degradable synthetic polymers was performed. Their rheological behaviours aided in setting process parameters for two different melt-based additive manufacturing routes. The variation in thermal degradation in the two routes was assessed, and the parameters were adjusted to minimise it.

A nondegradative additive manufacturing method was designed, and knowledge regarding printability was developed based on rheological analysis and polymer characterisation methods. This knowledge was applied to the copolymer poly(e-caprolactone-co-p-dioxanone) developed within the group to fabricate pliable scaffolds for tissue engineering with an increased rate of hydrolysis in comparison to poly(e-caprolactone). In addition to the selection of the polymer and process parameters, the mechanical properties were also controlled through the structural design. Poly(e-caprolactone) was used as a model material to show how the mechanical properties of scaffolds could be controlled based on the design solely. The results showed that the stiffness could be reduced by more than a factor of 10 through tuning of the design, resulting in soft pliable scaffold structures.

Place, publisher, year, edition, pages
KTH Royal Institute of Technology, 2021. p. 86
Series
TRITA-CBH-FOU ; 2021:7
National Category
Polymer Technologies
Research subject
Fibre and Polymer Science
Identifiers
urn:nbn:se:kth:diva-290799 (URN)978-91-7873-778-9 (ISBN)
Public defence
2021-03-26, https://kth-se.zoom.us/j/68298579714, Stockholm, 10:00 (English)
Opponent
Supervisors
Projects
Fibre and Polymer Science
Funder
Swedish Foundation for Strategic Research , RMA15-0010
Note

QC 2021-02-23

Available from: 2021-02-23 Created: 2021-02-23 Last updated: 2022-06-25Bibliographically approved
2. Engineering 3D degradable pliable scaffolds for adipose tissue regeneration: Advancing cell-material interactions by understanding the influence from thermal, chemical, mechanical properties and scaffold design
Open this publication in new window or tab >>Engineering 3D degradable pliable scaffolds for adipose tissue regeneration: Advancing cell-material interactions by understanding the influence from thermal, chemical, mechanical properties and scaffold design
2021 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In soft tissue defects that arise due to trauma, tumor resections and complex burns, a significant loss in adipose tissue remains a considerable challenge due to the insufficient regenerative capacity of the tissue. This thesis focuses on assessing cell-material interactions between degradable 3D polymer scaffolds with different designs and adipose tissue-derived stem cells. This knowledge can be used to engineer 3D scaffolds with adequate physio-chemical and mechanical properties along with an appropriate design that augments adipose tissue regeneration.

Salt-leaching 3D scaffolds were fabricated from various medical-grade polyesters, and cellular behavior was evaluated by correlating the physical, chemical, and mechanical properties of the scaffolds. The results showed that the glass transition temperature modulated the mechanical properties of the scaffolds, affecting stem cell proliferation and adipogenic differentiation. The same sets of polymers were further used in melt extrusion-based 3D printer and printability was established for the fabrication of customized 3D scaffolds. Based on printability and cell-scaffolds interaction results, poly (L-lactide-co-trimethylene carbonate) was used to print 3D scaffolds in different soft and pliable designs that promoted adipogenic differentiation. To fabricate even softer, and more hydrophilic 3D scaffolds, poly (ɛ-caprolactone-co-p-dioxanone) and a unique scaffold design were utilized within the research group. The copolymer 3D scaffolds were further combined with knitted mesh and electrospun nanofibers to develop scaffolds with multilayer architecture, modular scaffolds. The in vitro results asserted that the modular scaffold enhanced cell-material interactions by almost five times of those observed for the scaffold alone. Therefore, it can be concluded that softness and pliability are crucial and an appropriate scaffold design with adequate mechanical support is required for enhancing cell-material interaction. The in vitro results asserted that the modular scaffold enhanced cell-material interactions by almost five times of those observed for the scaffold alone. Therefore, it can be concluded that softness and pliability are crucial and an appropriate scaffold design with adequate mechanical support is required for enhancing cell-material interaction. The in vitro results asserted that the modular scaffold enhanced cell-material interactions by almost five times of those observed for the scaffold alone. Therefore, it can be concluded that softness and pliability are crucial and an appropriate scaffold design with adequate mechanical support is required for enhancing cell-material interaction.

Abstract [sv]

I mjukvävnadsdefekter som uppstår på grund av trauma, tumörresektioner och komplexa brännskador förblir en signifikant förlust av fettvävnad en utmaning på grund av vävnadens otillräckliga regenereringskapacitet. Denna avhandlingen fokuserar på att förstå interaktionerna mellan polymerer och celler, mellan nedbrytbara 3D-polymermatriser med olika design och stamceller som härrör från fettvävnad. Resultaten ger kunskap för att kunna skapa 3D-matriser med lämpliga fysikalisk-kemiska och mekaniska egenskaper som tillsammans med en lämplig design ger möjlighet för fettvävnadsregenerering.

Saltlakade 3D-matriser tillverkades av polyestrar av medicinsk kvalitet, cellernas beteende utvärderades för att korrelera matrisens fysiska, kemiska och mekaniska egenskaper. Resultaten visade att glasomvandlingstemperaturen påverkade matrisens mekaniska egenskaper, vilket i sin tur påverkade stamcellsförökning och den adipogena differentieringen. Samma uppsättning polymerer användes i en extruderbaserad 3D-skrivare för att tillverka 3D-matriser. Baserat på hur polymererna påverkades av 3D-skrivaren och resultat från interaktionerna mellan celler och polymerer valdes poly(L-laktid-sam-trimetylenkarbonat) för att skriva ut mjuka och böjbara 3D-matriser samt främja adipogen differentiering.För att tillverka ännu mjukare, böjliga och mer hydrofila 3D-matriser syntetiserades en ny polymer inom forskargruppen, poly(ɛ-kaprolakton-sam-p-dioxanon), och en unik matrisdesign togs fram. 3D-matrisen kombinerades vidare med stickade nät och elektrospunna nanofibrer för att utveckla multilagermatriser, modulmatriser. In vitro-resultaten visade att modulmatrisen förbättrade cell-materialinteraktionen nästan fem gånger i jämförelse med endast 3D-matrisen. Slutsatsen är att matrisens mjukhet och böjlighet är avgörande och att en anpassad matrisdesign med lämpligt mekaniskt stöd krävs för att förbättra cell-materialinteraktionen. 

Place, publisher, year, edition, pages
KTH Royal Institute of Technology, 2021. p. 124
Series
TRITA-CBH-FOU ; 2021:25
Keywords
Degradable polymers, 3D scaffolds, adipose tissue regeneration, cell-material interaction
National Category
Biomaterials Science Polymer Technologies
Research subject
Fibre and Polymer Science
Identifiers
urn:nbn:se:kth:diva-294176 (URN)978-91-7873-871-7 (ISBN)
Public defence
2021-06-11, https://kth-se.zoom.us/j/61588049521, Stockholm, 14:00 (English)
Opponent
Supervisors
Funder
Swedish Foundation for Strategic Research , RMA15-0010
Note

QC 2021-05-12

Available from: 2021-05-12 Created: 2021-05-11 Last updated: 2022-06-25Bibliographically approved

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Fuoco, TizianaAhlinder, AstridJain, ShubhamFinne Wistrand, Anna

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