Biomed. Eng.-Biomed. Tech. 2015; aop
Mandy-Nicole Birkholza, Garima Agrawala, Christian Bergmann, Ricarda Schröder, Sebastian J. Lechner, Andrij Pich* and Horst Fischer
Calcium phosphate/microgel composites for 3D powderbed printing of ceramic materials Abstract: Composites of microgels and calcium phosphates are promising as drug delivery systems and basic components for bone substitute implants. In this study, we synthesized novel composite materials consisting of pure β-tricalcium phosphate and stimuli-responsive poly(N-vinylcaprolactam-co-acetoacetoxyethyl methacrylate-co-vinylimidazole) microgels. The chemical composition, thermal properties and morphology for obtained composites were extensively characterized by Fourier transform infrared, X-ray photoelectron spectroscopy, IGAsorp moisture sorption analyzer, thermogravimetric analysis, granulometric analysis, ESEM, energy dispersive X-ray spectroscopy and TEM. Mechanical properties of the composites were evaluated by ball-on-three-balls test to determine the biaxial strength. Furthermore, initial 3D powderbed-based printing tests were conducted with spray-dried composites and diluted 2-propanol as a binder to evaluate a new binding concept for β-tricalcium phosphate-based granulates. The printed ceramic bodies were characterized before and after a sintering step by ESEM. The hypothesis that the microgels act as polymer adhesive agents by efficient chemical interactions with the β-tricalcium phosphate particles was confirmed. The obtained composites can be used for the development of new scaffolds. Keywords: 3D printing; β-tricalcium phosphate; bone substitute; composite; microgel.
a
MNB and GA have contributed equally to this work. *Corresponding author: Andrij Pich, Functional and Interactive Polymers, DWI, Leibniz Institute for Interactive Materials e.V., RWTH Aachen University, Forckenbeckstrasse 50, D-52056 Aachen, Germany, Phone: +49-241-8023310, Fax: +49-241-8023301, E-mail: [email protected] Mandy-Nicole Birkholz, Christian Bergmann and Horst Fischer: Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, Aachen, Germany Garima Agrawal, Ricarda Schröder and Sebastian J. Lechner: Functional and Interactive Polymers, DWI, Leibniz Institute for Interactive Materials e.V., RWTH Aachen University, Aachen, Germany
DOI 10.1515/bmt-2014-0141 Received October 28, 2014; accepted March 9, 2015
Introduction Special adapted porous ceramics [42] are required for different applications such as catalyst supports [46], (hollow fiber) membranes [18, 48] and bone-substitute implants [10, 38]. Our long-term goal is to create tailored bone substitutes using 3D-printing technologies. In this study, we examined β-tricalcium phosphate (β-TCP) in combination with microgels as a building block for the production of bone-substitute implants. For regenerative bone repair, biodegradable scaffolds with tailored porosity and strength are required [5, 10]. The established bone-substitute materials are β-TCP, composites of β-TCP and hydroxyapatite (HA) because of their biocompatibility and, especially for β-TCP, the resorption kinetics [12, 29]. Furthermore, β-TCP allows complete replacement by natural bone and is already in clinical application [11, 29, 33]. For example, an 8-cm-long intercalated rib defect in dogs could be repaired using β-TCP scaffolds [16]. Microgels are hydrated polymer networks that can be manufactured in sizes ranging from less than 0.1 to 1000 μm [30]. The binding capacity for water depends on an external stimulus such as temperature, pH value or ionic strength [9, 14, 31, 36]. Due to the small size and the large surface-to-volume ratio of the so-called stimuliresponsive microgels, the swelling/deswelling response occurs nearly instantaneously compared to macro-gels. Aside from their well-known use as superabsorbents in diapers, useful applications have been found in different areas due to the incorporation of biomacromolecules or inorganic nanoparticles. For example, microgels have been used as drug and gene delivery systems for nanomedical applications and as microreactors for the formation of inorganic nanoparticles [8, 28, 27, 35, 51]. Today, rapid prototyping methods like powderbedbased 3D printing allow building up tailored implants from CT-data and giving them a customized porosity
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2 M.-N. Birkholz et al.: Calcium phosphate/microgel composites for 3D printing
[3]. However, the printed green bodies are mechanically rather unstable. Normally, increasing stability requires high temperature sintering as a post-processing step or a completely hydraulic bone-cement reaction [13]. The latter method causes an unwanted loss of phase purity because of calcium hydrogen phosphate dihydrate (CHPD) formation due to the reaction of TCP and phosphoric acid [6]. In the 3D-printing process, a wide range of polymer additives can be used, ranging from synthetic to natural polymers or their mixtures to improve the printing process and properties of the composites [50]. Natural polymer additives such as polysaccharides are of plant (e.g., starch, dextrose, cellulose, etc.) or animal (e.g., sodium hyaluronate, collagen, etc.) origin or synthesized biotechnologically [microbial production of sodium hyaruronate or poly(hydroxybutyrate-co-hydroxyvalerate)]. Most of the natural polymers are biocompatible, biodegradable, hydrophilic and can be safely used in combination with water as a solvent for the fabrication of materials for medical applications via 3D printing [22, 43]. The main advantage of synthetic polymers is that they can be designed on-demand, and their properties, like molecular weight, chemical structure or chain architecture, can be customized to an actual need. However, many synthetic biocompatible and degradable polymers such as poly(e-caprolactone) (PCL) [15] or poly(lactic acid) (PLLA) [44] are often poorly soluble in aqueous media, so that organic solvents (e.g., chloroform) must be used, which raises toxicity issues [19, 39]. Therefore, new biocompatible aqueous polymer-binding systems and new composite materials are required to facilitate advanced 3D-processing methods to build-up customized scaffolds. Our hypothesis is that a combination of calcium phosphate granulate with microgels could have such advantages. In the presence of water, microgels may act as a soft water-based polymer-binding system to connect the calcium phosphate particles via intermolecular-interparticular-hydrogen bonding interactions [40]. Furthermore, the microgels could enhance the mechanical characteristics of printed scaffolds by improving particle bonding and because of their elasticity. In addition to variations in sintering temperature, the variation of microgel size and content may be useful in tailoring the porosity of the scaffolds. Only a few studies have been concerned with β-TCP microgel composites: (a) β-TCP encapsulated within chitosan microspheres (diameters of 200–400 μm); (b) freeze-dried scaffolds made up of poly(lactic acid) microspheres (diameters of 1–4 μm) and 4.8, 9.1 and 13.0 wt% β-TCP, respectively; and (c) an injectable composite of
alginate, β-TCP and poly(lactide-co-glycolide) microspheres for bone healing [21, 24, 47]. However, the composites mainly consist of pure β-TCP with homogeneously distributed microgels (size
Mandy-Nicole Birkholza, Garima Agrawala, Christian Bergmann, Ricarda Schröder, Sebastian J. Lechner, Andrij Pich* and Horst Fischer
Calcium phosphate/microgel composites for 3D powderbed printing of ceramic materials Abstract: Composites of microgels and calcium phosphates are promising as drug delivery systems and basic components for bone substitute implants. In this study, we synthesized novel composite materials consisting of pure β-tricalcium phosphate and stimuli-responsive poly(N-vinylcaprolactam-co-acetoacetoxyethyl methacrylate-co-vinylimidazole) microgels. The chemical composition, thermal properties and morphology for obtained composites were extensively characterized by Fourier transform infrared, X-ray photoelectron spectroscopy, IGAsorp moisture sorption analyzer, thermogravimetric analysis, granulometric analysis, ESEM, energy dispersive X-ray spectroscopy and TEM. Mechanical properties of the composites were evaluated by ball-on-three-balls test to determine the biaxial strength. Furthermore, initial 3D powderbed-based printing tests were conducted with spray-dried composites and diluted 2-propanol as a binder to evaluate a new binding concept for β-tricalcium phosphate-based granulates. The printed ceramic bodies were characterized before and after a sintering step by ESEM. The hypothesis that the microgels act as polymer adhesive agents by efficient chemical interactions with the β-tricalcium phosphate particles was confirmed. The obtained composites can be used for the development of new scaffolds. Keywords: 3D printing; β-tricalcium phosphate; bone substitute; composite; microgel.
a
MNB and GA have contributed equally to this work. *Corresponding author: Andrij Pich, Functional and Interactive Polymers, DWI, Leibniz Institute for Interactive Materials e.V., RWTH Aachen University, Forckenbeckstrasse 50, D-52056 Aachen, Germany, Phone: +49-241-8023310, Fax: +49-241-8023301, E-mail: [email protected] Mandy-Nicole Birkholz, Christian Bergmann and Horst Fischer: Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, Aachen, Germany Garima Agrawal, Ricarda Schröder and Sebastian J. Lechner: Functional and Interactive Polymers, DWI, Leibniz Institute for Interactive Materials e.V., RWTH Aachen University, Aachen, Germany
DOI 10.1515/bmt-2014-0141 Received October 28, 2014; accepted March 9, 2015
Introduction Special adapted porous ceramics [42] are required for different applications such as catalyst supports [46], (hollow fiber) membranes [18, 48] and bone-substitute implants [10, 38]. Our long-term goal is to create tailored bone substitutes using 3D-printing technologies. In this study, we examined β-tricalcium phosphate (β-TCP) in combination with microgels as a building block for the production of bone-substitute implants. For regenerative bone repair, biodegradable scaffolds with tailored porosity and strength are required [5, 10]. The established bone-substitute materials are β-TCP, composites of β-TCP and hydroxyapatite (HA) because of their biocompatibility and, especially for β-TCP, the resorption kinetics [12, 29]. Furthermore, β-TCP allows complete replacement by natural bone and is already in clinical application [11, 29, 33]. For example, an 8-cm-long intercalated rib defect in dogs could be repaired using β-TCP scaffolds [16]. Microgels are hydrated polymer networks that can be manufactured in sizes ranging from less than 0.1 to 1000 μm [30]. The binding capacity for water depends on an external stimulus such as temperature, pH value or ionic strength [9, 14, 31, 36]. Due to the small size and the large surface-to-volume ratio of the so-called stimuliresponsive microgels, the swelling/deswelling response occurs nearly instantaneously compared to macro-gels. Aside from their well-known use as superabsorbents in diapers, useful applications have been found in different areas due to the incorporation of biomacromolecules or inorganic nanoparticles. For example, microgels have been used as drug and gene delivery systems for nanomedical applications and as microreactors for the formation of inorganic nanoparticles [8, 28, 27, 35, 51]. Today, rapid prototyping methods like powderbedbased 3D printing allow building up tailored implants from CT-data and giving them a customized porosity
Brought to you by | New York University Bobst Library Technical Services Authenticated Download Date | 5/27/15 1:51 PM
2 M.-N. Birkholz et al.: Calcium phosphate/microgel composites for 3D printing
[3]. However, the printed green bodies are mechanically rather unstable. Normally, increasing stability requires high temperature sintering as a post-processing step or a completely hydraulic bone-cement reaction [13]. The latter method causes an unwanted loss of phase purity because of calcium hydrogen phosphate dihydrate (CHPD) formation due to the reaction of TCP and phosphoric acid [6]. In the 3D-printing process, a wide range of polymer additives can be used, ranging from synthetic to natural polymers or their mixtures to improve the printing process and properties of the composites [50]. Natural polymer additives such as polysaccharides are of plant (e.g., starch, dextrose, cellulose, etc.) or animal (e.g., sodium hyaluronate, collagen, etc.) origin or synthesized biotechnologically [microbial production of sodium hyaruronate or poly(hydroxybutyrate-co-hydroxyvalerate)]. Most of the natural polymers are biocompatible, biodegradable, hydrophilic and can be safely used in combination with water as a solvent for the fabrication of materials for medical applications via 3D printing [22, 43]. The main advantage of synthetic polymers is that they can be designed on-demand, and their properties, like molecular weight, chemical structure or chain architecture, can be customized to an actual need. However, many synthetic biocompatible and degradable polymers such as poly(e-caprolactone) (PCL) [15] or poly(lactic acid) (PLLA) [44] are often poorly soluble in aqueous media, so that organic solvents (e.g., chloroform) must be used, which raises toxicity issues [19, 39]. Therefore, new biocompatible aqueous polymer-binding systems and new composite materials are required to facilitate advanced 3D-processing methods to build-up customized scaffolds. Our hypothesis is that a combination of calcium phosphate granulate with microgels could have such advantages. In the presence of water, microgels may act as a soft water-based polymer-binding system to connect the calcium phosphate particles via intermolecular-interparticular-hydrogen bonding interactions [40]. Furthermore, the microgels could enhance the mechanical characteristics of printed scaffolds by improving particle bonding and because of their elasticity. In addition to variations in sintering temperature, the variation of microgel size and content may be useful in tailoring the porosity of the scaffolds. Only a few studies have been concerned with β-TCP microgel composites: (a) β-TCP encapsulated within chitosan microspheres (diameters of 200–400 μm); (b) freeze-dried scaffolds made up of poly(lactic acid) microspheres (diameters of 1–4 μm) and 4.8, 9.1 and 13.0 wt% β-TCP, respectively; and (c) an injectable composite of
alginate, β-TCP and poly(lactide-co-glycolide) microspheres for bone healing [21, 24, 47]. However, the composites mainly consist of pure β-TCP with homogeneously distributed microgels (size
