Additive manufacturing of bone-forming composite implants using photo-curable poly(trimethylene carbonate)-based resins

Mike Alexander Geven

Research output: ThesisPhD Thesis - Research UT, graduation UTAcademic

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Abstract

Bone tissue is generally able to perfectly restore and remodel itself after fracture or the formation of a defect due to traumatic injury or tumor removal. In some cases however, critical size bone defects are formed. These are of such size that the surrounding bone tissue is unable to restore the damaged site. Implantable and resorbable structures are then needed, to act as a temporary support and to induce de novo bone formation in the defect. Natural bone grafts currently outperform most synthetic implants. The use of natural grafts comes with several disadvantages however, such as risk for disease transmittance, graft rejection and limited options for shaping. Thus, novel synthetic implants are required which do not possess the disadvantages of natural grafts and perform similarly well.

This thesis describes the preparation and characterization of a novel composite material of photo-crosslinked, methacrylate end-group functionalized poly(trimethylene carbonate) (PTMC-MA) and nano-hydroxyapatite (nHA) particles.

These composites were prepared by two additive manufacturing techniques, in order to fabricate a material with a designed external as well as internal structure. Stereolithography was used to prepare well-fitting implants for defects with complex shapes. A low-temperature extrusion-based additive manufacturing technique was used to prepare composite structures with designed macro-scale porosity (several hundreds of micrometers) and micro-scale porosity (in the range of ten micrometer). The macro-scale porosity may allow for bone ingrowth, whereas the micro-scale porosity can allow for nutrient diffusion throughout the structure once implanted.

Composites produced by both techniques are cytocompatible and allow for osteogenic differentiation of human bone marrow mesenchymal stem cells on their surface. Furthermore, the nHA in the composites allows for an enhancement of their stiffness and toughness, the hydrophilicity and the resorbability. Composite structures prepared by stereolithography show a strong surface enrichment with nHA particles as the particle content is increased. This ultimately results in enhanced bone defect restoration and a better osseointegration of the structures in newly formed bone, as shown in small animal experiments.

Overall, the work in this thesis shows that composites of photo-crosslinked PTMC-MA and nHA may indeed be useful in bone tissue engineering applications.
Original languageEnglish
Awarding Institution
  • University of Twente
Supervisors/Advisors
  • Grijpma, D.W., Supervisor
  • Eglin, D., Supervisor
Thesis sponsors
Award date9 May 2018
Place of PublicationEnschede
Publisher
Print ISBNs978-90-365-4543-3
DOIs
Publication statusPublished - 9 May 2018

Fingerprint

3D printers
Bone
Resins
Composite materials
Durapatite
Grafts
Defects
Porosity
Stereolithography
Composite structures
Macros
polytrimethylene carbonate
Tissue
Methacrylates
Hydrophilicity
Stem cells
Tissue engineering
Nutrients
Restoration
Toughness

Cite this

@phdthesis{b7582f512f1646439537b104376c1fb2,
title = "Additive manufacturing of bone-forming composite implants using photo-curable poly(trimethylene carbonate)-based resins",
abstract = "Bone tissue is generally able to perfectly restore and remodel itself after fracture or the formation of a defect due to traumatic injury or tumor removal. In some cases however, critical size bone defects are formed. These are of such size that the surrounding bone tissue is unable to restore the damaged site. Implantable and resorbable structures are then needed, to act as a temporary support and to induce de novo bone formation in the defect. Natural bone grafts currently outperform most synthetic implants. The use of natural grafts comes with several disadvantages however, such as risk for disease transmittance, graft rejection and limited options for shaping. Thus, novel synthetic implants are required which do not possess the disadvantages of natural grafts and perform similarly well.This thesis describes the preparation and characterization of a novel composite material of photo-crosslinked, methacrylate end-group functionalized poly(trimethylene carbonate) (PTMC-MA) and nano-hydroxyapatite (nHA) particles. These composites were prepared by two additive manufacturing techniques, in order to fabricate a material with a designed external as well as internal structure. Stereolithography was used to prepare well-fitting implants for defects with complex shapes. A low-temperature extrusion-based additive manufacturing technique was used to prepare composite structures with designed macro-scale porosity (several hundreds of micrometers) and micro-scale porosity (in the range of ten micrometer). The macro-scale porosity may allow for bone ingrowth, whereas the micro-scale porosity can allow for nutrient diffusion throughout the structure once implanted.Composites produced by both techniques are cytocompatible and allow for osteogenic differentiation of human bone marrow mesenchymal stem cells on their surface. Furthermore, the nHA in the composites allows for an enhancement of their stiffness and toughness, the hydrophilicity and the resorbability. Composite structures prepared by stereolithography show a strong surface enrichment with nHA particles as the particle content is increased. This ultimately results in enhanced bone defect restoration and a better osseointegration of the structures in newly formed bone, as shown in small animal experiments.Overall, the work in this thesis shows that composites of photo-crosslinked PTMC-MA and nHA may indeed be useful in bone tissue engineering applications.",
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year = "2018",
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day = "9",
doi = "10.3990/1.9789036545433",
language = "English",
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Additive manufacturing of bone-forming composite implants using photo-curable poly(trimethylene carbonate)-based resins. / Geven, Mike Alexander.

Enschede : University of Twente, 2018. 195 p.

Research output: ThesisPhD Thesis - Research UT, graduation UTAcademic

TY - THES

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AU - Geven, Mike Alexander

PY - 2018/5/9

Y1 - 2018/5/9

N2 - Bone tissue is generally able to perfectly restore and remodel itself after fracture or the formation of a defect due to traumatic injury or tumor removal. In some cases however, critical size bone defects are formed. These are of such size that the surrounding bone tissue is unable to restore the damaged site. Implantable and resorbable structures are then needed, to act as a temporary support and to induce de novo bone formation in the defect. Natural bone grafts currently outperform most synthetic implants. The use of natural grafts comes with several disadvantages however, such as risk for disease transmittance, graft rejection and limited options for shaping. Thus, novel synthetic implants are required which do not possess the disadvantages of natural grafts and perform similarly well.This thesis describes the preparation and characterization of a novel composite material of photo-crosslinked, methacrylate end-group functionalized poly(trimethylene carbonate) (PTMC-MA) and nano-hydroxyapatite (nHA) particles. These composites were prepared by two additive manufacturing techniques, in order to fabricate a material with a designed external as well as internal structure. Stereolithography was used to prepare well-fitting implants for defects with complex shapes. A low-temperature extrusion-based additive manufacturing technique was used to prepare composite structures with designed macro-scale porosity (several hundreds of micrometers) and micro-scale porosity (in the range of ten micrometer). The macro-scale porosity may allow for bone ingrowth, whereas the micro-scale porosity can allow for nutrient diffusion throughout the structure once implanted.Composites produced by both techniques are cytocompatible and allow for osteogenic differentiation of human bone marrow mesenchymal stem cells on their surface. Furthermore, the nHA in the composites allows for an enhancement of their stiffness and toughness, the hydrophilicity and the resorbability. Composite structures prepared by stereolithography show a strong surface enrichment with nHA particles as the particle content is increased. This ultimately results in enhanced bone defect restoration and a better osseointegration of the structures in newly formed bone, as shown in small animal experiments.Overall, the work in this thesis shows that composites of photo-crosslinked PTMC-MA and nHA may indeed be useful in bone tissue engineering applications.

AB - Bone tissue is generally able to perfectly restore and remodel itself after fracture or the formation of a defect due to traumatic injury or tumor removal. In some cases however, critical size bone defects are formed. These are of such size that the surrounding bone tissue is unable to restore the damaged site. Implantable and resorbable structures are then needed, to act as a temporary support and to induce de novo bone formation in the defect. Natural bone grafts currently outperform most synthetic implants. The use of natural grafts comes with several disadvantages however, such as risk for disease transmittance, graft rejection and limited options for shaping. Thus, novel synthetic implants are required which do not possess the disadvantages of natural grafts and perform similarly well.This thesis describes the preparation and characterization of a novel composite material of photo-crosslinked, methacrylate end-group functionalized poly(trimethylene carbonate) (PTMC-MA) and nano-hydroxyapatite (nHA) particles. These composites were prepared by two additive manufacturing techniques, in order to fabricate a material with a designed external as well as internal structure. Stereolithography was used to prepare well-fitting implants for defects with complex shapes. A low-temperature extrusion-based additive manufacturing technique was used to prepare composite structures with designed macro-scale porosity (several hundreds of micrometers) and micro-scale porosity (in the range of ten micrometer). The macro-scale porosity may allow for bone ingrowth, whereas the micro-scale porosity can allow for nutrient diffusion throughout the structure once implanted.Composites produced by both techniques are cytocompatible and allow for osteogenic differentiation of human bone marrow mesenchymal stem cells on their surface. Furthermore, the nHA in the composites allows for an enhancement of their stiffness and toughness, the hydrophilicity and the resorbability. Composite structures prepared by stereolithography show a strong surface enrichment with nHA particles as the particle content is increased. This ultimately results in enhanced bone defect restoration and a better osseointegration of the structures in newly formed bone, as shown in small animal experiments.Overall, the work in this thesis shows that composites of photo-crosslinked PTMC-MA and nHA may indeed be useful in bone tissue engineering applications.

U2 - 10.3990/1.9789036545433

DO - 10.3990/1.9789036545433

M3 - PhD Thesis - Research UT, graduation UT

SN - 978-90-365-4543-3

PB - University of Twente

CY - Enschede

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