A drug eluting poly(Trimethylene carbonate)/ poly(lactic acid)-reinforced nanocomposite for the functional delivery of osteogenic molecules

Xi Zhang, Mike A. Geven, Xinluan Wang, Ling Qin, Dirk W. Grijpma, Ton Peijs, David Eglin, Olivier Guillaume, Julien E. Gautrot (Corresponding Author)

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Abstract

Background: Poly(trimethylene carbonate) (PTMC) has wide biomedical applications in the field of tissue engineering, due to its biocompatibility and biodegradability features. Its common manufacturing involves photofabrication, such as stereolithography (SLA), which allows the fabrication of complex and controlled structures. Despite the great potential of SLA-fabricated scaffolds, very few examples of PTMC-based drug delivery systems fabricated using photofabrication can be found ascribed to light-triggered therapeutics instability, degradation, side reaction, binding to the macromers, etc. These concerns severely restrict the development of SLA-fabricated PTMC structures for drug delivery purposes. Methods: In this context, we propose here, as a proof of concept, to load a drug model (dex-amethasone) into electrospun fibers of poly(lactic acid), and then to integrate these bioactive fibers into the photo-crosslinkable resin of PTMC to produce hybrid films. The hybrid films’ properties and drug release profile were characterized; its biological activity was investigated via bone marrow mesenchymal stem cells culture and differentiation assays. Results: The polymer/polymer hybrids exhibit improved properties compared with PTMC-only films, in terms of mechanical performance and drug protection from UV denaturation. We further validated that the dexamethasone preserved its biological activity even after photoreaction within the PTMC/poly(lactic acid) hybrid structures by investigating bone marrow mesenchymal stem cells proliferation and osteogenic differentiation. Conclusion: This study demonstrates the potential of polymer–polymer scaffolds to simultaneously reinforce the mechanical properties of soft matrices and to load sensitive drugs in scaffolds that can be fabricated via additive manufacturing.

Original languageEnglish
Pages (from-to)5701-5718
Number of pages18
JournalInternational journal of nanomedicine
Volume13
DOIs
Publication statusPublished - 1 Jan 2018

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Nanocomposites
Lactic acid
Carbonates
Stereolithography
Molecules
Scaffolds
Pharmaceutical Preparations
Bioactivity
Stem cells
Mesenchymal Stromal Cells
Polymers
Bone
3D printers
Bone Marrow
Denaturation
Fibers
Biodegradability
Cell proliferation
Drug Delivery Systems
Tissue Engineering

Keywords

  • Dexamethasone
  • Fiber-reinforced composite
  • Osteogenic materials
  • Photo-crosslinking
  • Poly(trimethylene carbonate)

Cite this

Zhang, Xi ; Geven, Mike A. ; Wang, Xinluan ; Qin, Ling ; Grijpma, Dirk W. ; Peijs, Ton ; Eglin, David ; Guillaume, Olivier ; Gautrot, Julien E. / A drug eluting poly(Trimethylene carbonate)/ poly(lactic acid)-reinforced nanocomposite for the functional delivery of osteogenic molecules. In: International journal of nanomedicine. 2018 ; Vol. 13. pp. 5701-5718.
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abstract = "Background: Poly(trimethylene carbonate) (PTMC) has wide biomedical applications in the field of tissue engineering, due to its biocompatibility and biodegradability features. Its common manufacturing involves photofabrication, such as stereolithography (SLA), which allows the fabrication of complex and controlled structures. Despite the great potential of SLA-fabricated scaffolds, very few examples of PTMC-based drug delivery systems fabricated using photofabrication can be found ascribed to light-triggered therapeutics instability, degradation, side reaction, binding to the macromers, etc. These concerns severely restrict the development of SLA-fabricated PTMC structures for drug delivery purposes. Methods: In this context, we propose here, as a proof of concept, to load a drug model (dex-amethasone) into electrospun fibers of poly(lactic acid), and then to integrate these bioactive fibers into the photo-crosslinkable resin of PTMC to produce hybrid films. The hybrid films’ properties and drug release profile were characterized; its biological activity was investigated via bone marrow mesenchymal stem cells culture and differentiation assays. Results: The polymer/polymer hybrids exhibit improved properties compared with PTMC-only films, in terms of mechanical performance and drug protection from UV denaturation. We further validated that the dexamethasone preserved its biological activity even after photoreaction within the PTMC/poly(lactic acid) hybrid structures by investigating bone marrow mesenchymal stem cells proliferation and osteogenic differentiation. Conclusion: This study demonstrates the potential of polymer–polymer scaffolds to simultaneously reinforce the mechanical properties of soft matrices and to load sensitive drugs in scaffolds that can be fabricated via additive manufacturing.",
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A drug eluting poly(Trimethylene carbonate)/ poly(lactic acid)-reinforced nanocomposite for the functional delivery of osteogenic molecules. / Zhang, Xi; Geven, Mike A.; Wang, Xinluan; Qin, Ling; Grijpma, Dirk W.; Peijs, Ton; Eglin, David; Guillaume, Olivier; Gautrot, Julien E. (Corresponding Author).

In: International journal of nanomedicine, Vol. 13, 01.01.2018, p. 5701-5718.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Zhang, Xi

AU - Geven, Mike A.

AU - Wang, Xinluan

AU - Qin, Ling

AU - Grijpma, Dirk W.

AU - Peijs, Ton

AU - Eglin, David

AU - Guillaume, Olivier

AU - Gautrot, Julien E.

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N2 - Background: Poly(trimethylene carbonate) (PTMC) has wide biomedical applications in the field of tissue engineering, due to its biocompatibility and biodegradability features. Its common manufacturing involves photofabrication, such as stereolithography (SLA), which allows the fabrication of complex and controlled structures. Despite the great potential of SLA-fabricated scaffolds, very few examples of PTMC-based drug delivery systems fabricated using photofabrication can be found ascribed to light-triggered therapeutics instability, degradation, side reaction, binding to the macromers, etc. These concerns severely restrict the development of SLA-fabricated PTMC structures for drug delivery purposes. Methods: In this context, we propose here, as a proof of concept, to load a drug model (dex-amethasone) into electrospun fibers of poly(lactic acid), and then to integrate these bioactive fibers into the photo-crosslinkable resin of PTMC to produce hybrid films. The hybrid films’ properties and drug release profile were characterized; its biological activity was investigated via bone marrow mesenchymal stem cells culture and differentiation assays. Results: The polymer/polymer hybrids exhibit improved properties compared with PTMC-only films, in terms of mechanical performance and drug protection from UV denaturation. We further validated that the dexamethasone preserved its biological activity even after photoreaction within the PTMC/poly(lactic acid) hybrid structures by investigating bone marrow mesenchymal stem cells proliferation and osteogenic differentiation. Conclusion: This study demonstrates the potential of polymer–polymer scaffolds to simultaneously reinforce the mechanical properties of soft matrices and to load sensitive drugs in scaffolds that can be fabricated via additive manufacturing.

AB - Background: Poly(trimethylene carbonate) (PTMC) has wide biomedical applications in the field of tissue engineering, due to its biocompatibility and biodegradability features. Its common manufacturing involves photofabrication, such as stereolithography (SLA), which allows the fabrication of complex and controlled structures. Despite the great potential of SLA-fabricated scaffolds, very few examples of PTMC-based drug delivery systems fabricated using photofabrication can be found ascribed to light-triggered therapeutics instability, degradation, side reaction, binding to the macromers, etc. These concerns severely restrict the development of SLA-fabricated PTMC structures for drug delivery purposes. Methods: In this context, we propose here, as a proof of concept, to load a drug model (dex-amethasone) into electrospun fibers of poly(lactic acid), and then to integrate these bioactive fibers into the photo-crosslinkable resin of PTMC to produce hybrid films. The hybrid films’ properties and drug release profile were characterized; its biological activity was investigated via bone marrow mesenchymal stem cells culture and differentiation assays. Results: The polymer/polymer hybrids exhibit improved properties compared with PTMC-only films, in terms of mechanical performance and drug protection from UV denaturation. We further validated that the dexamethasone preserved its biological activity even after photoreaction within the PTMC/poly(lactic acid) hybrid structures by investigating bone marrow mesenchymal stem cells proliferation and osteogenic differentiation. Conclusion: This study demonstrates the potential of polymer–polymer scaffolds to simultaneously reinforce the mechanical properties of soft matrices and to load sensitive drugs in scaffolds that can be fabricated via additive manufacturing.

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