From Unregulated Networks to Designed Microstructures: Introducing Heterogeneity at Different Length Scales in Photopolymers for Additive Manufacturing.

Photopolymers have been optimized as protective and decorative coating materials for decades. However, with the rise of additive manufacturing technologies, vat photopolymerization has unlocked the use of photopolymers for three-dimensional objects with new material requirements. Thus, the originally highly cross-linked, amorphous architecture of photopolymers cannot match the expectations for modern materials anymore, revealing the largely unanswered question of how diverse properties can be achieved in photopolymers. Herein, we review how microstructural features in soft matter materials should be designed and implemented to obtain high performance materials. We then translate these findings into chemical design suggestions for enhanced printable photopolymers. Based on this analysis, we have found microstructural heterogenization to be the most powerful tool to tune photopolymer performance. By combining the chemical toolbox for photopolymerization and the analytical toolbox for microstructural characterization, we examine current strategies for physical heterogenization (fillers, inkjet printing) and chemical heterogenization (semicrystalline polymers, block copolymers, interpenetrating networks, photopolymerization induced phase separation) of photopolymers and put them into a material scientific context to develop a roadmap for improving and diversifying photopolymers' performance.

Polymers for 3D Printing and Customized Additive Manufacturing.

Additive manufacturing (AM) alias 3D printing translates computer-aided design (CAD) virtual 3D models into physical objects. By digital slicing of CAD, 3D scan, or tomography data, AM builds objects layer by layer without the need for molds or machining. AM enables decentralized fabrication of customized objects on demand by exploiting digital information storage and retrieval via the Internet. The ongoing transition from rapid prototyping to rapid manufacturing prompts new challenges for mechanical engineers and materials scientists alike. Because polymers are by far the most utilized class of materials for AM, this Review focuses on polymer processing and the development of polymers and advanced polymer systems specifically for AM. AM techniques covered include vat photopolymerization (stereolithography), powder bed fusion (SLS), material and binder jetting (inkjet and aerosol 3D printing), sheet lamination (LOM), extrusion (FDM, 3D dispensing, 3D fiber deposition, and 3D plotting), and 3D bioprinting. The range of polymers used in AM encompasses thermoplastics, thermosets, elastomers, hydrogels, functional polymers, polymer blends, composites, and biological systems. Aspects of polymer design, additives, and processing parameters as they relate to enhancing build speed and improving accuracy, functionality, surface finish, stability, mechanical properties, and porosity are addressed. Selected applications demonstrate how polymer-based AM is being exploited in lightweight engineering, architecture, food processing, optics, energy technology, dentistry, drug delivery, and personalized medicine. Unparalleled by metals and ceramics, polymer-based AM plays a key role in the emerging AM of advanced multifunctional and multimaterial systems including living biological systems as well as life-like synthetic systems.

Laser photofabrication of cell-containing hydrogel constructs.

The two-photon polymerization (2PP) of photosensitive gelatin in the presence of living cells is reported. The 2PP technique is based on the localized cross-linking of photopolymers induced by femtosecond laser pulses. The availability of water-soluble photoinitiators (PI) suitable for 2PP is crucial for applying this method to cell-containing materials. Novel PIs developed by our group allow 2PP of formulations with up to 80% cell culture medium. The cytocompatibility of these PIs was evaluated by an MTT assay. The results of cell encapsulation by 2PP show the occurrence of cell damage within the laser-exposed regions. However, some cells located in the immediate vicinity and even within the 2PP-produced structures remain viable and can further proliferate. The control experiments demonstrate that the laser radiation itself does not damage the cells at the parameters used for 2PP. On the basis of these findings and the reports by other groups, we conclude that such localized cell damage is of a chemical origin and can be attributed to reactive species generated during 2PP. The viable cells trapped within the 2PP structures but not exposed to laser radiation continued to proliferate. The live/dead staining after 3 weeks revealed viable cells occupying most of the space available within the 3D hydrogel constructs. While some of the questions raised by this study remain open, the presented results indicate the general practicability of 2PP for 3D processing of cell-containing materials. The potential applications of this highly versatile approach span from precise engineering of 3D tissue models to the fabrication of cellular microarrays.

Hierarchically porous materials from layer-by-layer photopolymerization of high internal phase emulsions.

A combination of high internal phase emulsion (HIPE) templating and additive manufacturing technology (AMT) is applied for creating hierarchical porosity within an acrylate and acrylate/thiol-based polymer network. The photopolymerizable formulation is optimized to produce emulsions with a volume fraction of droplet phase greater than 80 vol%. Kinetic stability of the emulsions is sufficient enough to withstand in-mold curing or computer-controlled layer-by-layer stereolithography without phase separation. By including macroscale cellular cavities within the build file, a level of controlled porosity is created simultaneous to the formation of the porous microstructure of the polyHIPE. The hybrid HIPE-AMT technique thus provides hierarchically porous materials with mechanical properties tailored by the addition of thiol chain transfer agent.

A Martini 3 coarse-grain model for the simulation of the photopolymerizable organic phase in dental composites.

Light-hardening dental composites can be used in a large number of applications in restorative dentistry. They are based on photopolymerizable resins, which are highly relevant also in other industries like 3D printing. Much effort is therefore being put into developing and optimizing photopolymers. Currently used photopolymers still have limitations regarding mechanical properties, shrinkage and leaching of uncured monomers. These issues are strongly linked to the network structure of the polymer and are usually addressed using trial and error methods. Therefore, it is of interest to have a model for the network structure of such materials and to have a tool to facilitate scientific progress and the development of high-performance photopolymers. This work presents a coarse grain model of Bis-GMA/TEGDMA formulations and their corresponding networks, following the Martini 3 guidelines and using a simulated polymerization algorithm. The model proved to reproduce the densities and volumetric shrinkage values found in the literature well. Furthermore, it was possible to estimate the final double bond conversion of the polymer material. Martini's building block-like design makes it easy to extend the model to other monomers in the future.

The Role of Solvents in Lithography-Based Ceramic Manufacturing of Lithium Disilicate.

Digital dentistry is increasingly replacing conventional methods of manually producing dental restorations. With regards to computer-aided manufacturing (CAM), milling is state of the art. Additive manufacturing (AM), as a complementary approach, has also found its way into dental practices and laboratories. Vat photo-polymerization is gaining increasing attention, because it enables the production of full ceramic restorations with high precision. One of the two predominantly used ceramic materials for these applications is lithium disilicate, Li2Si2O5. This glass ceramic exhibits a substantial fracture toughness, although possesses much lower bending strength, than the other predominantly used ceramic material, zirconia. Additionally, it shows a much more natural optical appearance, due to its inherent translucency, and therefore is considered for anterior tooth restorations. In this work, an optimized formulation for photo-reactive lithium disilicate suspensions, to be processed by vat photo-polymerization, is presented. Following the fundamental theoretical considerations regarding this processing technique, a variety of solvents was used to adjust the main properties of the suspension. It is shown that this solvent approach is a useful tool to effectively optimize a suspension with regards to refractive index, rheology, and debinding behavior. Additionally, by examining the effect of the absorber, the exposure time could be reduced by a factor of ten.

Bio-Inspired Toughening of Composites in 3D-Printing.

Natural materials achieve exceptional mechanical properties by relying on hierarchically structuring their internal architecture. In several marine species, layers of stiff and hard inorganic material are separated by thin compliant organic layers, giving their skeleton both stiffness and toughness. This phenomenon is fundamentally based on the periodical variation of Young's modulus within the structure. In this study, alteration of mechanical properties is achieved through a layer-wise build-up of two different materials. A hybrid 3D-printing device combining stereolithography and inkjet printing is used for the manufacturing process. Both components used in this system, the ink for jetting and the resin for structuring by stereolithography (SLA), are acrylate-based and photo-curable. Layers of resin and ink are solidified separately using two different light sources (λ1 = 375 nm, λ2 = 455 nm). Three composite sample groups (i.e., one hybrid material, two control groups) are built. Measurements reveal an increase in fracture toughness and elongation at break of 70% and 22%, respectively, for the hybrid material compared to the control groups. Moreover, the comparison of the two control groups shows that the effect is essentially dependent on different materials being well contained within separated layers. This bio-inspired building approach increases fracture toughness of an inherently brittle matrix material.

Stereolithographic Additive Manufacturing of High Precision Glass Ceramic Parts.

Lithography based additive manufacturing (AM) is one of the most established and widely used 3D-printing processes. It has enabled the processing of many different materials from thermoplast-like polymers to ceramics that have outstanding feature resolutions and surface quality, with comparable properties of traditional materials. This work focuses on the processing of glass ceramics, which have high optical demands, precision and mechanical properties specifically suitable for dental replacements, such as crowns. Lithography-based ceramic manufacturing (LCM) has been chosen as the optimal manufacturing process where a light source with a defined wavelength is used to cure and structure ceramic filled photosensitive resins. In the case of glass ceramic powders, plastic flow during thermal processing might reduce the precision, as well as the commonly observed sintering shrinkage associated with the utilized temperature program. To reduce this problem, particular sinter structures have been developed to optimize the precision of 3D-printed glass ceramic crowns. To evaluate the precision of the final part, testing using digitizing methods from optical to tactile systems were utilized with the best results were obtained from micro computed tomography (CT) scanning. These methods resulted in an optimized process allowing for possible production of high precision molar crowns with dimensional accuracy and high reproducibility.

Stereolithography-based additive manufacturing of lithium disilicate glass ceramic for dental applications.

With additive manufacturing (AM) on the rise in industrial production, different industries are looking for a way to benefit from the advantages over conventional manufacturing methods like milling or casting. The layer by layer approach allows the parallel construction of different complex structures with simultaneous customization of the parts, while waste material is significantly reduced. This is especially interesting for the processing of advanced ceramic materials, where often customized and single parts are required. Regarding ceramics, Lithographic Ceramic Manufacturing (LCM) provides the highest surface quality and achievable precision compared to any other AM technologies, which is necessary to meet the high demands from dental industry regarding accuracy and reproducibility. At TU Wien, we achieved expertise in printing different kinds of ceramics and glasses by using specially developed stereolithography printers based on digital light processing (DLP) followed by a thermal debinding and sintering processes. In dental industry, glass ceramic materials are widely used for customized and aesthetic restorations. This work deals with the processing of lithium disilicate via an AM technology, offering highly dense (>99%), full ceramic parts which meet the requirements for the use as dental restorations. With outstanding mechanical properties of over 400 MPa flexural strength, excellent translucency and accuracy, veneers, crowns and even bridges, especially for the anterior tooth area can be reproducibly printed, debinded and sintered.

UV-Induced Cationic Ring-Opening Polymerization of 2-Oxazolines for Hot Lithography.

The cationic ring-opening polymerization (CROP) of 2-oxazolines gives polymers with unique characteristics arising from its polyamide backbones and structural versatility. Up to now, poly(2-oxazoline)s were obtained by classical thermal polymerization methods not aiming for application in bulk curing of structural polymers. We introduce the cationic photopolymerization of 2-oxazolines at elevated temperatures for the direct UV-induced curing of materials with exclusive chemical and structural particularities. After efficient photoinitiation via onium salt photoacid generators (PAGs), the immanent low-rate propagation is crucially promoted by thermal energy input to the ring-opening reaction. In simultaneous thermal analysis (STA), photo-DSC, and (thermo)mechanical analyses we investigated the UV-induced CROP of 2-oxazolines in a temperature range of 100-140 °C and show the exceptional potential of the introduced photopolymers. Furthermore, we applied the photopolymerizable system in Hot Lithography, a stereolithography-based 3D printing technology at elevated temperatures.

A highly efficient waterborne photoinitiator for visible-light-induced three-dimensional printing of hydrogels.

A bis(acyl)phosphane oxide (BAPO) photoinitiator was conveniently synthesized in an efficient one-pot process. It shows excellent dispersibility in water, good storage stability, and high photo-reactivity in 3D printing of hydrogels under visible-light irradiation (460 nm).

Visible Light Photoinitiator for 3D-Printing of Tough Methacrylate Resins.

Lithography-based additive manufacturing was introduced in the 1980s, and is still the method of choice for printing accurate plastic parts with high surface quality. Recent progress in this field has made tough photopolymer resins and cheap LED light engines available. This study presents the influence of photoinitiator selection and post-processing on the thermomechanical properties of various tough photopolymers. The influence of three photoinitiators (Ivocerin, BAPO, and TPO-L) on the double-bond conversion and mechanical properties was investigated by mid infrared spectroscopy, dynamic mechanical analysis and tensile tests. It was found that 1.18 wt % TPO-L would provide the best overall results in terms of double-bond conversion and mechanical properties. A correlation between double-bond conversion, yield strength, and glass transition temperature was found. Elongation at break remained high after post-curing at about 80-100%, and was not influenced by higher photoinitiator concentration. Finally, functional parts with 41 MPa tensile strength, 82% elongation at break, and 112 °C glass transition temperature were printed on a 405 nm DLP (digital light processing) printer.

Laser 3D printing with sub-microscale resolution of porous elastomeric scaffolds for supporting human bone stem cells.

A reproducible method is needed to fabricate 3D scaffold constructs that results in periodic and uniform structures with precise control at sub-micrometer and micrometer length scales. In this study, fabrication of scaffolds by two-photon polymerization (2PP) of a biodegradable urethane and acrylate-based photoelastomer is demonstrated. This material supports 2PP processing with sub-micrometer spatial resolution. The high photoreactivity of the biophotoelastomer permits 2PP processing at a scanning speed of 1000 mm s(-1), facilitating rapid fabrication of relatively large structures (>5 mm(3)). These structures are custom printed for in vitro assay screening in 96-well plates and are sufficiently flexible to enable facile handling and transplantation. These results indicate that stable scaffolds with porosities of greater than 60% can be produced using 2PP. Human bone marrow stromal cells grown on 3D scaffolds exhibit increased growth and proliferation compared to smooth 2D scaffold controls. 3D scaffolds adsorb larger amounts of protein than smooth 2D scaffolds due to their larger surface area; the scaffolds also allow cells to attach in multiple planes and to completely infiltrate the porous scaffolds. The flexible photoelastomer material is biocompatible in vitro and is associated with facile handling, making it a viable candidate for further study of complex 3D-printed scaffolds.

3D alkyne-azide cycloaddition: spatiotemporally controlled by combination of aryl azide photochemistry and two-photon grafting.

A novel fluoroaryl azide with an alkyne tail was synthesized and precisely immobilized within a PEG-based matrix via two-photon induced decomposition and nitrene insertion. Well defined 3D positioning of the terminal alkyne allows site-specific micropatterning. The subsequent 3D alkyne-azide cycloaddition was realized using dye-functionalized molecules containing "clickable" azide moieties.

High-fidelity, inexpensive surgical middle ear simulator.

HYPOTHESIS: A high-fidelity, inexpensive middle ear simulator could be created to enhance surgical training that would be rated as having high face validity by experts. BACKGROUND: With rapid prototyping using additive manufacturing technology (AMT), one can create high-resolution 3-dimensional replicas of the middle ear at low cost and high fidelity. Such a simulator could be of great benefit for surgical training, particularly in light of new resident training guidelines. METHODS: AMT was used to create surgical middle ear simulator (SMS) with 2 different materials simulating bone and soft tissue. The simulator is composed of an outer box with dimensions of an average adult external auditory canal without scutum and an inner cartridge based on an otosclerosis model. The simulator was then rated by otology experts in terms of face validity and fidelity as well as their opinion on the usefulness of such a device. RESULTS: Eighteen otologists from 6 tertiary academic centers rated the simulator; 83.3% agreed or highly agreed that SMS has accurate dimensions and 66.6% that it has accurate tactile feedback. When asked if performance of stapedotomy with the SMS improves with practice, 46% agreed. As to whether practicing stapedotomy with the SMS translates to improvement with live surgery, 78% agreed with this statement. Experts' average rating of the components of SMS (of possible 5) was as follows: middle ear dimensions, 3.9; malleus, 3.7; incus, 3.6; stapes, 3.6; chorda tympani, 3.7; tensor tympani, 4.1; stapedius, 3.8; facial nerve, 3.7; and promontory, 3.5. Overall, 83% found SMS to be at least "very useful" in training of novices, particularly for junior and senior residents. CONCLUSION: Most experts found the SMS to be accurate, but there was a large discrepancy in rating of individual components. Most found it to be very useful for training of novice surgeons. With these results, we are encouraged to proceed with further refinements that will strengthen the SMS as a training tool for otologic surgery.

Photo-sensitive hydrogels for three-dimensional laser microfabrication in the presence of whole organisms.

Hydrogels are polymeric materials with water contents similar to that of soft tissues. Due to their biomimetic properties, they have been extensively used in various biomedical applications including cell encapsulation for tissue engineering. The utilization of photopolymers provides a possibility for the temporal and spatial controlling of hydrogel cross-links. We produced three-dimensional (3-D) hydrogel scaffolds by means of the two-photon polymerization (2PP) technique. Using a highly efficient water-soluble initiator, photopolymers with up to 80 wt.% water were processed with high precision and reproducibility at a writing speed of 10 mm/s. The biocompatibility of the applied materials was verified using Caenorhabditis elegans as living test organisms. Furthermore, these living organisms were successfully embedded within a 200×200×35 µm³ hydrogel scaffold. As most biologic tissues exhibit a window of transparency at the wavelength of the applied femtosecond laser, it is suggested that 2PP is promising for an in situ approach. Our results demonstrate the feasibility of and potential for bio-fabricating 3-D tissue constructs in the micrometre-range via near-infrared lasers in direct contact with a living organism.

Elastomeric degradable biomaterials by photopolymerization-based CAD-CAM for vascular tissue engineering.

A predominant portion of mortalities in industrial countries can be attributed to diseases of the cardiovascular system. In the last decades great efforts have been undertaken to develop materials for artificial vascular constructs. However, bio-inert materials like ePTFE or PET fail as material for narrow blood vessel replacements (coronary bypasses). Therefore, we aim to design new biocompatible materials to overcome this. In this paper we investigate the use of photoelastomers for artificial vascular constructs since they may be precisely structured by means of additive manufacturing technologies. Hence, 3D computer aided design and manufacturing technologies (CAD-CAM) offer the possibility of creating cellular structures within the grafts that might favour ingrowth of tissue. Different monomer formulations were screened concerning their suitability for this application but all had drawbacks, especially concerning the suture tear resistance. Therefore, we chose to modify the original network architecture by including dithiol chain transfer agents which effectively co-react with the acrylates and reduce crosslink density. A commercial urethane diacrylate was chosen as base monomer. In combination with reactive diluents and dithiols, the properties of the photopolymers could be tailored and degradability could be introduced. The optimized photoelastomers were in good mechanical accordance with native blood vessels, showed good biocompatibility in in vitro tests, degraded similar to poly(lactic acid) and were successfully manufactured with the 3D CAD-CAM technology.

In vitro determination of biomechanical properties of human articular cartilage in osteoarthritis using multi-parametric MRI.

The objective of this study was to evaluate the correlations between MR parameters and the biomechanical properties of naturally degenerated human articular cartilage. Human cartilage explants from the femoral condyles of patients who underwent total knee replacement were evaluated on a micro-imaging system at 3T. To quantify glycosaminoglycan (GAG) content, delayed gadolinium-enhanced MRI of the cartilage (dGEMRIC) was used. T(2) maps were created by using multi-echo, multi-slice spin echo sequences with six echoes: 15, 30, 45, 60, 75, and 90 ms. Data for apparent diffusion constant (ADC) maps were obtained from pulsed gradient spin echo (PGSE) sequences with five b-values: 10.472, 220.0, 627.0, 452.8, 724.5, and 957.7. MR parameters were correlated with mechanical parameters (instantaneous (I) and equilibrium (Eq) modulus and relaxation time (tau)), and the OA stage of each cartilage specimen was determined by histological evaluation of hematoxylin-eosin stained slices. For some parameters, a high correlation was found: the correlation of T(1Gd) vs Eq (r=0.8095), T(1Gd) vs I/Eq (r=-0.8441) and T(1Gd) vs tau (r=0.8469). The correlation of T(2) and ADC with selected biomechanical parameters was not statistically significant. In conclusion, GAG content measured by dGEMRIC is highly related to the selected biomechanical properties of naturally degenerated articular cartilage. In contrast, T(2) and ADC were unable to estimate these properties. The results of the study imply that some MR parameters can non-invasively predict the biomechanical properties of degenerated articular cartilage.