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Dirk W. Grijpma - One of the best experts on this subject based on the ideXlab platform.
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photo crosslinked synthetic biodegradable polymer networks for biomedical applications
Journal of Biomaterials Science-polymer Edition, 2019Co-Authors: Bas Van Bochove, Dirk W. GrijpmaAbstract:Photo-crosslinked synthetic biodegradable polymer networks are highly interesting materials for utilization in biomedical applications such as drug delivery, cell encapsulation and tissue engineering scaffolds. Varying the architecture, chemistry, degree of functionalization and molecular weight of the macromer precursor molecules results in networks with a wide range of physical- and mechanical properties, crosslinking densities, degradation characteristics and thus in potential applications. Photo-crosslinked networks can easily be prepared and have the possibility to entrap a wide range of (biologically active) substances and cells. Additionally, spatial and temporal control over the crosslinking process when using additive manufacturing processes, allows for the preparation of network structures with complex shapes. Photo-crosslinked networks have been used to prepare drug delivery devices, as these networks allow for drug delivery in a controlled way over a prolonged period of time. Furthermore, additive manufacturing techniques such as extrusion-based additive manufacturing and stereolithography have been used to prepare photo-crosslinked tissue engineering scaffolds. This allows for the preparation of designed porous structures with precise control over the pore size and pore architecture and optimal mechanical properties. In particular for stereolithography, a wide variety of resins based on biodegradable photo-crosslinkable Macromers has been developed.
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Preparation of Designed Poly(trimethylene carbonate) Meniscus Implants by Stereolithography: Challenges in Stereolithography
Macromolecular Bioscience, 2016Co-Authors: Bas Van Bochove, Gerjon Hannink, Pieter Buma, Dirk W. GrijpmaAbstract:Three-armed poly(trimethylene carbonate) Macromers with a relatively high molecular weight of 28.9 kg mol−1 are prepared by ring opening polymerization and subsequent functionalization with methacrylate end groups. A resin suitable for processing by stereolithography is developed using propylene carbonate as a diluent, a photoinitiator, and a dye to control the curing char- acteristics. The difficulties in building designed structures with digital light processing stereo- lithography and the ways of optimizing the resin compositions are described in detail. Using an optimized resin composition, which contained 50 wt% macromer, 50 wt% diluent, 0.05 wt% (relative to the macromer) dye, and 5 wt% (relative to the macromer) photoinitiator, designed 3D porous structures with a gyroid pore network geometry are manufactured. By varying pore sizes and porosities between, respectively, 300 and 1000 µm and 60% and 90%, cylindrical porous poly(trimethylene carbonate) network structures with compression moduli of 85–2320 kPa are prepared. A porous poly(trimethylene carbonate) network meniscus implant is designed on the basis of computed tomography imaging data. By adjusting the characteristics of the gyroid pore architec- ture, an implant with a compression modulus close to 400 kPa, which fits the compression modulus of human meniscal tissue, is manufactured by stereolithography
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rapid photo crosslinking of fumaric acid monoethyl ester functionalized poly trimethylene carbonate oligomers for drug delivery applications
Journal of Controlled Release, 2010Co-Authors: Janine Jansen, Mark Johannes Boerakker, Jean Heuts, Jan Feijen, Dirk W. GrijpmaAbstract:Photo-crosslinkable, fumaric acid monoethyl ester-functionalized poly(trimethylene carbonate) oligomers were synthesized and copolymerized with N-vinyl pyrrolidone (NVP) and vinyl acetate (VAc) to form biodegradable polymer networks. The copolymerization reactions were much faster than homopolymerization of the fumarate end-groups of the Macromers. The hydrophilicity of the networks could by varied by mixing NVP and VAc at different ratios. The prepared network extracts were compatible with NIH 3T3 fibroblasts. Release of vitamin B12, used as a model drug, could be tuned by varying network hydrophilicity and macromer molecular weight. A more hydrophilic and less densely crosslinked network resulted in faster release.
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a poly d l lactide resin for the preparation of tissue engineering scaffolds by stereolithography
Biomaterials, 2009Co-Authors: Ferry P W Melchels, Jan Feijen, Dirk W. GrijpmaAbstract:Porous polylactide constructs were prepared by stereolithography, for the first time without the use of reactive diluents. Star-shaped poly(d,l-lactide) oligomers with 2, 3 and 6 arms were synthesised, end-functionalised with methacryloyl chloride and photo-crosslinked in the presence of ethyl lactate as a non-reactive diluent. The molecular weights of the arms of the Macromers were 0.2, 0.6, 1.1 and 5 kg/mol, allowing variation of the crosslink density of the resulting networks. Networks prepared from Macromers of which the molecular weight per arm was 0.6 kg/mol or higher had good mechanical properties, similar to linear high-molecular weight poly(d,l-lactide). A resin based on a 2-armed poly(d,l-lactide) macromer with a molecular weight of 0.6 kg/mol per arm (75 wt%), ethyl lactate (19 wt%), photo-initiator (6 wt%), inhibitor and dye was prepared. Using this resin, films and computer-designed porous constructs were accurately fabricated by stereolithography. Pre-osteoblasts showed good adherence to these photo-crosslinked networks. The proliferation rate on these materials was comparable to that on high-molecular weight poly(d,l-lactide) and tissue culture polystyrene.
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creep resistant elastomeric networks prepared by photocrosslinking fumaric acid monoethyl ester functionalized poly trimethylene carbonate oligomers
Acta Biomaterialia, 2009Co-Authors: Dirk W. Grijpma, Jan FeijenAbstract:Biodegradable elastomeric networks were prepared from ethyl fumarate-functionalized poly(trimethylene carbonate) oligomers. Photocrosslinkable Macromers were synthesized by reacting three-armed, hydroxyl group-terminated poly(trimethylene carbonate) oligomers with fumaric acid monoethyl ester at room temperature using N,N-dicyclohexylcarbodiimide as a coupling agent and 4-dimethylamino pyridine as a catalyst. Poly(trimethylene carbonate) Macromers with molecular weights ranging between 4500 and 13,900 were prepared and crosslinked by ultraviolet-initiated radical polymerization. The gel contents of the resulting transparent networks varied between 74% and 80%. All obtained networks had low glass transition temperatures, which varied between −18 and −13 °C. They showed rubber-like behavior and excellent mechanical properties, with tensile strengths and elongations at break of up to 17.5 MPa and 750%, respectively. Moreover, static- and dynamic creep experiments showed that these amorphous networks were highly elastic and resistant to creep. In cyclic tensile testing to 50% strain, the permanent deformation after 20 cycles was 0%, while static creep tests at 35% of the yield stress did not indicate creep or permanent deformation after removal of the load. Porous structures were prepared by photopolymerizing the Macromers in the presence of salt particles, and subsequent leaching of the salt. Such networks, built up of non-toxic compounds and designed to release benign degradation products, may find application as tissue engineering scaffolds for dynamic cell culture.
Jason A Burdick - One of the best experts on this subject based on the ideXlab platform.
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influence of hyaluronic acid modification on cd44 binding towards the design of hydrogel biomaterials
Biomaterials, 2019Co-Authors: Mi Y Kwon, Chao Wang, Jonathan H Galarraga, Ellen Pure, Lin Han, Jason A BurdickAbstract:Hyaluronic acid (HA) is a linear polysaccharide of d-glucuronic acid and N-acetyl-d-glucosamine that is native to many tissues and interacts with cells via cell-surface receptors (e.g., CD44). HA has been extensively explored as a chemically-modified macromer for crosslinking into biomaterials, such as hydrogels and macroporous scaffolds. However, the influence of the extent and type of HA modification on its binding to CD44 is not well understood or quantified. To address this, we modified HA at either the carboxylic acid or the primary alcohol with various chemical groups (e.g., norbornenes, methacrylates) and magnitudes (~10, 20, or 40% of disaccharides) and then characterized binding in both soluble and hydrogel forms. HA binding to CD44 immobilized on plates or presented by cells was influenced by the extent and type of its modification, where increased modification (i.e., ~40%) generally decreased binding. The adhesion of CD44-modified beads to hydrogels as measured by atomic force microscopy revealed a similar trend, particularly with decreased adhesion with hydrophobic modifications to the carboxylic acid. Further, the chondrogenesis of mesenchymal stromal cells when encapsulated in hydrogels fabricated from modified HA Macromers was reduced at high modification, behaving similarly to inert hydrogel controls. This work suggests that the types and extents of modification of polysaccharides are important factors that should be considered in preserving their biological function when processed as hydrogels.
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norbornene modified poly glycerol sebacate as a photocurable and biodegradable elastomer
Polymer Chemistry, 2017Co-Authors: Yicheun Yeh, Liliang Ouyang, Christopher B. Highley, Jason A BurdickAbstract:Poly(glycerol sebacate) (PGS) is a biodegradable elastomer that has emerged as a promising material in biomedical applications; however, the traditional thermal crosslinking of PGS limits its processing in the fabrication of three-dimensional (3D) scaffolds. Here, we designed a new photocurable PGS that uses thiol–ene click chemistry to control PGS crosslinking. Specifically, norbornene-functionalized PGS (Nor-PGS) Macromers were crosslinked by varied amounts of a 4-arm thiolated crosslinker to program properties such as mechanics and degradation. The Nor-PGS crosslinked rapidly (<1 min to plateau modulus) under ultraviolet light and the storage modulus was dependent on the crosslinker amount, with a maximum storage modulus observed with an equimolar norbornene/thiol ratio. Tensile properties of Nor-PGS were also altered by the crosslinker concentration, with a simultaneous increase in elastic modulus and failure stress and decrease in elongation (ranging from ∼170–240%) with higher crosslinker concentrations. In turn, the degradation of Nor-PGS was faster with lower crosslinker concentrations. To illustrate the processing of Nor-PGS, porous scaffolds with a range of sizes and shapes were fabricated using extrusion-based 3D printing, where the viscous macromer was extruded and crosslinked with continuous ultraviolet light exposure. Printed scaffolds supported the culture and proliferation of fibroblasts. These results indicate that crosslinked Nor-PGS is a promising functional elastomer for the fabrication of property-controllable scaffolds for biomedical applications.
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3D printing of photocurable poly(glycerol sebacate) elastomers
Biofabrication, 2016Co-Authors: Christopher B. Highley, Liliang Ouyang, Jason A BurdickAbstract:Three-dimensional (3D) printed scaffolds have great potential in biomedicine; however, it is important that we are able to design such scaffolds with a range of diverse properties towards specific applications. Here, we report the extrusion-based 3D printing of biodegradable and photocurable acrylated polyglycerol sebacate (Acr-PGS) to fabricate scaffolds with elastic properties. Two Acr-PGS Macromers were synthesized with varied molecular weights and viscosity, which were then blended to obtain photocurable macromer inks with a range of viscosities. The quality of extruded and photocured scaffolds was dependent on the initial ink viscosity, with flow of printed material resulting in a loss of structural resolution or sample breaking observed with too low or too high viscosity inks, respectively. However, scaffolds with high print resolution and up to ten layers were fabricated with an optimal ink viscosity. The mechanical properties of printed scaffolds were dependent on printing density, where the scaffolds with lower printing density possessed lower moduli and failure properties than higher density scaffolds. The 3D printed scaffolds supported the culture of 3T3 fibroblasts and both spreading and proliferation were observed, indicating that 3D printed Acr-PGS scaffolds are cytocompatible. These results demonstrate that Acr-PGS is a promising material for the fabrication of elastomeric scaffolds for biomedical applications.
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rational design of network properties in guest host assembled and shear thinning hyaluronic acid hydrogels
Biomacromolecules, 2013Co-Authors: Christopher B Rodell, Adam L Kaminski, Jason A BurdickAbstract:Shear-thinning hydrogels afford direct injection or catheter delivery to tissues without potential premature gel formation and delivery failure or the use of triggers such as chemical initiators or heat. However, many shear-thinning hydrogels require long reassembly times or exhibit rapid erosion. We developed a shear-thinning hyaluronic acid (HA) hydrogel based on the guest–host interactions of adamantane modified HA (guest macromer, Ad-HA) and β-cyclodextrin modified HA (host macromer, CD-HA). The ability of the guest and host molecules to interact with their counterpart following conjugation to HA was confirmed by 1H NMR spectroscopy and was similar to that of the native complex. Mixing of Ad-HA and CD-HA resulted in rapid formation of a hydrogel composed of guest–host bonds. The hydrogel physical properties, including mechanics and flow characteristics, were dependent on cross-link density and network structure, which were controlled through macromer concentration, the extent of guest macromer modific...
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biodegradable fibrous scaffolds with tunable properties formed from photo cross linkable poly glycerol sebacate
ACS Applied Materials & Interfaces, 2009Co-Authors: Jamie L Ifkovits, Jeffrey J Devlin, George Eng, Timothy P Martens, Gordana Vunjaknovakovic, Jason A BurdickAbstract:It is becoming increasingly apparent that the architecture and mechanical properties of scaffolds, particularly with respect to mimicking features of natural tissues, are important for tissue engineering applications. Acrylated poly(glycerol sebacate) (Acr-PGS) is a material that can be cross-linked upon exposure to ultraviolet light, leading to networks with tunable mechanical and degradation properties through simple changes during Acr-PGS synthesis. For example, the number of acrylate functional groups on the macromer dictates the concentration of cross-links formed in the resulting network. Three Macromers were synthesized that form networks that vary dramatically with respect to their tensile modulus (∼30 kPa to 6.6 MPa) and degradation behavior (∼20−100% mass loss at 12 weeks) based on the extent of acrylation (∼1−24%). These Macromers were processed into biodegradable fibrous scaffolds using electrospinning, with gelatin as a carrier polymer to facilitate fiber formation and cell adhesion. The resu...
Jan Feijen - One of the best experts on this subject based on the ideXlab platform.
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rapid photo crosslinking of fumaric acid monoethyl ester functionalized poly trimethylene carbonate oligomers for drug delivery applications
Journal of Controlled Release, 2010Co-Authors: Janine Jansen, Mark Johannes Boerakker, Jean Heuts, Jan Feijen, Dirk W. GrijpmaAbstract:Photo-crosslinkable, fumaric acid monoethyl ester-functionalized poly(trimethylene carbonate) oligomers were synthesized and copolymerized with N-vinyl pyrrolidone (NVP) and vinyl acetate (VAc) to form biodegradable polymer networks. The copolymerization reactions were much faster than homopolymerization of the fumarate end-groups of the Macromers. The hydrophilicity of the networks could by varied by mixing NVP and VAc at different ratios. The prepared network extracts were compatible with NIH 3T3 fibroblasts. Release of vitamin B12, used as a model drug, could be tuned by varying network hydrophilicity and macromer molecular weight. A more hydrophilic and less densely crosslinked network resulted in faster release.
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a poly d l lactide resin for the preparation of tissue engineering scaffolds by stereolithography
Biomaterials, 2009Co-Authors: Ferry P W Melchels, Jan Feijen, Dirk W. GrijpmaAbstract:Porous polylactide constructs were prepared by stereolithography, for the first time without the use of reactive diluents. Star-shaped poly(d,l-lactide) oligomers with 2, 3 and 6 arms were synthesised, end-functionalised with methacryloyl chloride and photo-crosslinked in the presence of ethyl lactate as a non-reactive diluent. The molecular weights of the arms of the Macromers were 0.2, 0.6, 1.1 and 5 kg/mol, allowing variation of the crosslink density of the resulting networks. Networks prepared from Macromers of which the molecular weight per arm was 0.6 kg/mol or higher had good mechanical properties, similar to linear high-molecular weight poly(d,l-lactide). A resin based on a 2-armed poly(d,l-lactide) macromer with a molecular weight of 0.6 kg/mol per arm (75 wt%), ethyl lactate (19 wt%), photo-initiator (6 wt%), inhibitor and dye was prepared. Using this resin, films and computer-designed porous constructs were accurately fabricated by stereolithography. Pre-osteoblasts showed good adherence to these photo-crosslinked networks. The proliferation rate on these materials was comparable to that on high-molecular weight poly(d,l-lactide) and tissue culture polystyrene.
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creep resistant elastomeric networks prepared by photocrosslinking fumaric acid monoethyl ester functionalized poly trimethylene carbonate oligomers
Acta Biomaterialia, 2009Co-Authors: Dirk W. Grijpma, Jan FeijenAbstract:Biodegradable elastomeric networks were prepared from ethyl fumarate-functionalized poly(trimethylene carbonate) oligomers. Photocrosslinkable Macromers were synthesized by reacting three-armed, hydroxyl group-terminated poly(trimethylene carbonate) oligomers with fumaric acid monoethyl ester at room temperature using N,N-dicyclohexylcarbodiimide as a coupling agent and 4-dimethylamino pyridine as a catalyst. Poly(trimethylene carbonate) Macromers with molecular weights ranging between 4500 and 13,900 were prepared and crosslinked by ultraviolet-initiated radical polymerization. The gel contents of the resulting transparent networks varied between 74% and 80%. All obtained networks had low glass transition temperatures, which varied between −18 and −13 °C. They showed rubber-like behavior and excellent mechanical properties, with tensile strengths and elongations at break of up to 17.5 MPa and 750%, respectively. Moreover, static- and dynamic creep experiments showed that these amorphous networks were highly elastic and resistant to creep. In cyclic tensile testing to 50% strain, the permanent deformation after 20 cycles was 0%, while static creep tests at 35% of the yield stress did not indicate creep or permanent deformation after removal of the load. Porous structures were prepared by photopolymerizing the Macromers in the presence of salt particles, and subsequent leaching of the salt. Such networks, built up of non-toxic compounds and designed to release benign degradation products, may find application as tissue engineering scaffolds for dynamic cell culture.
Antonios G Mikos - One of the best experts on this subject based on the ideXlab platform.
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Synthesis and Characterization of Diol-Based Unsaturated Polyesters: Poly(diol fumarate) and Poly(diol fumarate-co-succinate)
2017Co-Authors: Alexander M. Tatara, Paul S. Engel, Emma Watson, Tejus Satish, David W. Scott, Dimitrios P. Kontoyiannis, Antonios G MikosAbstract:In this work, we describe the synthesis and characterization of variants of poly(diol fumarate) and poly(diol fumarate-co-succinate). Through a Fischer esterification, α,ω-diols and dicarboxylic acids were polymerized to form aliphatic polyester coMacromers. Because of the carbon-carbon double bond of fumaric acid, incorporating it into the macromer backbone structure resulted in unsaturated chains. By choosing α,ω-diols of different lengths (1,6-hexanediol, 1,8-octanediol, and 1,10-decanediol) and controlling the amount of fumaric acid in the dicarboxylic acid monomer feed (33, 50, and 100 mol %), nine diol-based macromer variants were synthesized and characterized for molecular weight, number of unsaturated bonds per chain, and thermal properties. Degradation and in vitro cytotoxicity were also measured in a subset of Macromers. As proof-of-principle, macromer networks were photo-cross-linked to demonstrate the ability to perform free radical addition using the unsaturated macromer backbone. Cross-linked macromer networks were also characterized for physicochemical properties (swelling, sol fraction, compressive modulus) based on diol length and amount of unsaturated bonds. A statistical model was built using data generated from these diol-based Macromers and macromer networks to evaluate the impact of monomer inputs on final macromer and macromer network properties. With the ability to be modified by free radical addition, biodegradable unsaturated polyesters serve as important Macromers in the design of devices such as drug delivery vehicles and tissue scaffolds. Given the ability to extensively control final macromer properties based on monomer input parameters, poly(diol fumarate) and poly(diol fumarate-co-succinate) represent an exciting new class of Macromers
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Synthesis and Characterization of Injectable, Biodegradable, Phosphate-Containing, Chemically Cross-Linkable,
2016Co-Authors: Thermoresponsive Macromers, Brendan M. Watson, Paul S. Engel, Kurtis F Kasper, Bone Tissue Engineering, Antonios G MikosAbstract:ABSTRACT: Novel, injectable, biodegradable macromer solutions that form hydrogels when elevated to physiologic temperature via a dual chemical and thermo-gelation were fabricated and characterized. A thermogelling, poly(N-isopropylacrylamide)-based macromer with pendant phos-phate groups was synthesized and subsequently functionalized with chemically cross-linkable methacrylate groups via degradable phosphate ester bonds, yielding a dual-gelling macromer. These dual-gelling Macromers were tuned to have transition temperatures between room temperature and physiologic temperature, allowing them to undergo instantaneous thermogelation as well as chemical gelation when elevated to physiologic temperature. Additionally, the chemical cross-linking of the hydrogels was shown to mitigate hydrogel syneresis, which commonly occurs when thermogelling materials are raised above their transition temperature. Finally, degradation of the phosphate ester bonds of the cross-linked hydrogels yielded Macromers that were soluble at physiologic temperature. Further characterization of the hydrogels demonstrated minimal cytotoxicity of hydrogel leachables as well as in vitro calcification, making these novel, injectable Macromers promising materials for use in bon
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Synthesis and characterization of injectable, biodegradable, phosphate-containing, chemically cross-linkable, thermoresponsive Macromers for bone tissue engineering
Biomacromolecules, 2014Co-Authors: Brendan M. Watson, F. Kurtis Kasper, Paul S. Engel, Antonios G MikosAbstract:Novel, injectable, biodegradable macromer solutions that form hydrogels when elevated to physiologic temperature via a dual chemical and thermo-gelation were fabricated and characterized. A thermogelling, poly(N-isopropylacrylamide)-based macromer with pendant phosphate groups was synthesized and subsequently functionalized with chemically cross-linkable methacrylate groups via degradable phosphate ester bonds, yielding a dual-gelling macromer. These dual-gelling Macromers were tuned to have transition temperatures between room temperature and physiologic temperature, allowing them to undergo instantaneous thermogelation as well as chemical gelation when elevated to physiologic temperature. Additionally, the chemical cross-linking of the hydrogels was shown to mitigate hydrogel syneresis, which commonly occurs when thermogelling materials are raised above their transition temperature. Finally, degradation of the phosphate ester bonds of the cross-linked hydrogels yielded Macromers that were soluble at physiologic temperature. Further characterization of the hydrogels demonstrated minimal cytotoxicity of hydrogel leachables as well as in vitro calcification, making these novel, injectable Macromers promising materials for use in bone tissue engineering.
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thermoresponsive in situ cross linkable hydrogels based on n isopropylacrylamide fabrication characterization and mesenchymal stem cell encapsulation
Acta Biomaterialia, 2011Co-Authors: Leda Klouda, Brendan M. Watson, Stephanie J Bryant, Kevin R Perkins, Michael C Hacker, Robert M Raphael, Kurtis F Kasper, Antonios G MikosAbstract:Hydrogels that solidify in response to a dual, physical and chemical, mechanism upon temperature increase were fabricated and characterized. The hydrogels were based on N-isopropylacrylamide, which renders them thermoresponsive, and contained covalently cross-linkable moieties in the Macromers. The effects of the macromer end group, acrylate or methacrylate, and the fabrication conditions on the degradative and swelling properties of the hydrogels were investigated. The hydrogels exhibited higher swelling below their lower critical solution temperature (LCST). When immersed in cell culture medium at physiological temperature, which was above their LCST, hydrogels showed constant swelling and no degradation over 8 weeks, with the methacrylated hydrogels showing greater swelling than their acrylated analogs. In addition, hydrogels immersed in cell culture medium under the same conditions showed lower swelling compared with phosphate-buffered saline. The interplay between chemical cross-linking and thermally induced phase separation affected the swelling characteristics of the hydrogels in different media. Mesenchymal stem cells encapsulated in the hydrogels in vitro were viable over 3 weeks and markers of osteogenic differentiation were detected when the cells were cultured with osteogenic supplements. Hydrogel mineralization in the absence of cells was observed in cell culture medium with the addition of fetal bovine serum and β-glycerol phosphate. The results suggest that these hydrogels may be suitable as carriers for cell delivery in tissue engineering.
Grijpma, Dirk W. - One of the best experts on this subject based on the ideXlab platform.
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Osteogenic differentiation of hBMSCs on porous photo-crosslinked poly(trimethylene carbonate) and nano-hydroxyapatite composites
'Elsevier BV', 2021Co-Authors: Geven, Mike A., Lapomarda Anna, Guillaume Olivier, Sprecher, Christoph M., Eglin David, Vozzi Giovanni, Grijpma, Dirk W.Abstract:Large bone defects are challenging to repair and novel implantable materials are needed to aid in their reconstruction. Research in the past years has proven the beneficial effect of porosity in an implant on osteogenesis in vivo. Building on this research we report here on porous composites based on photo-crosslinked poly(trimethylene carbonate) and nano-hydroxyapatite. These composites were prepared by a temperature induced phase separation of poly(trimethylene carbonate) Macromers from solution in ethylene carbonate. By controlling the ethylene carbonate content in viscous dispersions of nano-hydroxyapatite in poly(trimethylene carbonate) macromer solutions, composites with 40 wt% nano-hydroxyapatite and 27 to 71% porosity were prepared. The surface structure of these porous composites was affected by their porosity and their topography became dominated by deep micro-pore channels with the majority of pore widths below 20 µm and rougher surfaces on the nano-scale. The stiffness and toughness of the composites decreased with increasing porosity from 67 to 3.5 MPa and 263 to 2.2 N/mm2, respectively. In cell culture experiments, human bone marrow mesenchymal stem cells proliferated well on the composites irrespective of their porosity. Furthermore, differentiation of the cells was demonstrated by determination of ALP activity and calcium production. The extent of differentiation was affected by the porosity of the films, offering a reduced mechanical incentive for osteogenic differentiation at higher porosities with topographies likely offering a reduced possibility for cells to aggregate and to elongate into morphologies favourable for osteogenic differentiation. This ultimately resulted in a 3-fold reduction of calcium production of the differentiated cells on composites with 71% porosity compared to those on composites with 27% porosity
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Photo-Crosslinked Elastomeric Bimodal Poly(trimethylene carbonate) Networks
2019Co-Authors: Van Bochove Bas, Schüller-ravoo Sigrid, Grijpma, Dirk W.Abstract:Using methacrylated poly(trimethylene carbonate) oligomers unimodal (prepared from one macromer) and bimodal (prepared from two Macromers with different molecular weights) photo-crosslinked networks and structures are prepared by stereolithography. The obtained biodegradable networks are flexible and elastic. Compared to the corresponding unimodal networks, the tensile properties of bimodal poly(trimethylene carbonate) (PTMC) network films are significantly enhanced. Resilient materials with increased toughness and suture retention strengths are obtained. The mechanical properties of the bimodal networks compare favorably with those of unimodal networks prepared previously from PTMC Macromers with much higher molecular weights. Tough porous PTMC structures with designed diamond pore network architectures can also be readily prepared by stereolithography. Upon swelling of these PTMC structures in a solvent, the pore sizes and pore size distribution increases while the porosity decreases
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Microstructured Photo-Crosslinked Poly(Trimethylene Carbonate) for Use in Soft Lithography Applications: A Biodegradable Alternative for Poly(Dimethylsiloxane)
2018Co-Authors: Schüller-ravoo Sigrid, Teixeira, Sandra M., Papenburg Bernke, Stamatialis Dimitrios, Feijen Jan, Grijpma, Dirk W.Abstract:Photo-crosslinkable poly(trimethylene carbonate) (PTMC) Macromers were used to fabricate microstructured surfaces. Microstructured PTMC surfaces were obtained by hot embossing the macromer against structured silicon masters and subsequent photo-crosslinking, resulting in network formation. The microstructures of the master could be precisely replicated, limiting the shrinkage. Microstructured PTMC was investigated for use in two different applications: as stamping material to transfer a model protein to another surface and as structured substrate for cell culture. Using the flexible and elastic materials as stamps, bovine serum albumin labelled with fluorescein isothiocyanate was patterned on glass surfaces. In cell culture experiments, the behavior of human mesenchymal stem cells on nonstructured and microstructured PTMC surfaces was investigated. The cells strongly adhered to the PTMC surfaces and proliferated well. Compared to poly(dimethylsiloxane) (PDMS), which is commonly used in soft lithography, the PTMC networks offer significant advantages. They show better compatibility with cells, are biodegradable, and have much better mechanical properties. Both materials are transparent, flexible, and elastic at room temperature, but the tear resistance of PTMC networks is much higher than that of PDMS. Thus, PTMC might be an alternative material to PDMS in the fields of biology, medicine, and tissue engineering, in which microfabricated devices are increasingly being applied
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Degradation behavior of, and tissue response to photo-crosslinked poly(trimethylene carbonate) networks
2016Co-Authors: Rongen, Jan J., Grijpma, Dirk W., Van Bochove Bas, Hannink Gerjon, Buma PieterAbstract:Photo-crosslinked networks prepared from three-armed methacrylate functionalized PTMC oligomers (PTMC-tMA Macromers) are attractive materials for developing an anatomically correct meniscus scaffold. In this study, we evaluated cell specific biocompatibility, in vitro and in vivo degradation behavior of, and tissue response to, such PTMC networks. By evaluating PTMC networks prepared from PTMC-tMA Macromers of different molecular weights, we were able to assess the effect of macromer molecular weight on the degradation rate of the PTMC network obtained after photo-crosslinking. Three photo-crosslinked networks with different crosslinking densities were prepared using PTMC-tMA Macromers with molecular weights 13.3, 17.8, and 26.7 kg/mol. Good cell biocompatibility was demonstrated in a proliferation assay with synovium derived cells. PTMC networks degraded slowly, but statistically significant, both in vitro as well as subcutaneously in rats. Networks prepared fromMacromers with higher molecular weights demonstrated increased degradation rates compared to networks prepared from initial Macromers of lowest molecular weight. The degradation process took place via surface erosion. The PTMC networks showed good tissue tolerance during subcutaneous implantation, to which the tissue response was characterized by the presence of fibrous tissue and encapsulation of the implants. Concluding, we developed cell and tissue biocompatible, photo-crosslinked PTMC networks using PTMC-tMA Macromers with relatively high molecular weights. These photo-crosslinked PTMC networks slowly degrade by a surface erosion process. Increasing the crosslinking density of these networks decreases the rate of surface degradation. (C) 2016 Wiley Periodicals, Inc
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Tough biodegradable mixed-macromer networks and hydrogels by photo-crosslinking in solution
'Elsevier BV', 2016Co-Authors: Zant E., Grijpma, Dirk W.Abstract:The preparation of polymeric networks that are both tough and biodegradable remains a challenge. Here we show a very straightforward method to produce tough biodegradable networks from low molecular weight Macromers for applications such as tissue engineering. Photo-crosslinking combinatorial mixtures of methacrylate-functionalized poly(1,3-trimethylene carbonate) (PTMC), poly(d,l-lactide) (PDLLA), poly(ε-caprolactone) (PCL) and poly(ethylene glycol) (PEG) oligomers in propylene carbonate (PC) allowed the preparation of network films with excellent tensile characteristics and resistance to tearing. This method enabled the production of both very tough mixed-macromer elastomers as well as mixed-macromer hydrogels. A mixed-macromer hydrogel prepared from 33 wt.% PTMC, 33 wt.% PCL and 33 wt.% PEG had a very high tearing energy of 0.81 kJ/m2, which is comparable to tearing energies determined for articular cartilage
