Browsing by Subject "3D printing"

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  • Germini, Giorgia; Peltonen, Leena (2021)
    The aim of the study was to prepare indomethacin nanocrystal-loaded, 3D-printed, fast-dissolving oral polymeric film formulations. Nanocrystals were produced by the wet pearl milling technique, and 3D printing was performed by the semi-solid extrusion method. Hydroxypropyl methyl cellulose (HPMC) was the film-forming polymer, and glycerol the plasticizer. In-depth physicochemical characterization was made, including solid-state determination, particle size and size deviation analysis, film appearance evaluation, determination of weight variation, thickness, folding endurance, drug content uniformity, and disintegration time, and drug release testing. In drug nanocrystal studies, three different stabilizers were tested. Poloxamer F68 produced the smallest and most homogeneous particles, with particle size values of 230 nm and PI values below 0.20, and was selected as a stabilizer for the drug-loaded film studies. In printing studies, the polymer concentration was first optimized with drug-free formulations. The best mechanical film properties were achieved for the films with HPMC concentrations of 2.85% (w/w) and 3.5% (w/w), and these two HPMC levels were selected for further drug-loaded film studies. Besides, in the drug-loaded film printing studies, three different drug levels were tested. With the optimum concentration, films were flexible and homogeneous, disintegrated in 1 to 2.5 min, and released the drug in 2-3 min. Drug nanocrystals remained in the nano size range in the polymer films, particle sizes being in all film formulations from 300 to 500 nm. When the 3D-printed polymer films were compared to traditional film-casted polymer films, the physicochemical behavior and pharmaceutical performance of the films were very similar. As a conclusion, 3D printing of drug nanocrystals in oral polymeric film formulations is a very promising option for the production of immediate-release improved- solubility formulations.
  • Shaqour, Bahaa; Reigada, Ines; Gorecka, Zaneta; Choinska, Emilia; Verleije, Bart; Beyers, Koen; Swieszkowski, Wojciech; Fallarero, Adyary; Cos, Paul (2020)
    Additive manufacturing technologies have been widely used in the medical field. More specifically, fused filament fabrication (FFF) 3D-printing technology has been thoroughly investigated to produce drug delivery systems. Recently, few researchers have explored the possibility of directly 3D printing such systems without the need for producing a filament which is usually the feedstock material for the printer. This was possible via direct feeding of a mixture consisting of the carrier polymer and the required drug. However, as this direct feeding approach shows limited homogenizing abilities, it is vital to investigate the effect of the pre-mixing step on the quality of the 3D printed products. Our study investigates the two commonly used mixing approaches-solvent casting and powder mixing. For this purpose, polycaprolactone (PCL) was used as the main polymer under investigation and gentamicin sulfate (GS) was selected as a reference. The produced systems' efficacy was investigated for bacterial and biofilm prevention. Our data show that the solvent casting approach offers improved drug distribution within the polymeric matrix, as was observed from micro-computed topography and scanning electron microscopy visualization. Moreover, this approach shows a higher drug release rate and thus improved antibacterial efficacy. However, there were no differences among the tested approaches in terms of thermal and mechanical properties.
  • Pernaa, Johannes; Wiedmer, Susanne (2020)
    The focus of this systematic literature analysis is to provide a comprehensive review of earlier research on the utilisation of 3D printers in chemistry education. The objective is to offer research-based knowledge for developing chemistry education through following research questions: what kind of work has been done in the field of 3D printing in chemistry education; what kind of design strategies have been implemented; how 3D printing has been used in chemistry education research. The data consists of 47 peer-reviewed articles which were analysed via qualitative content analysis using a technological pedagogical content knowledge framework. Theoretical framework was selected because integrating 3D printing in chemistry education requires knowledge of chemistry, technology, and most importantly, pedagogy. Our research indicates that integrating 3D printing begins by analysing current challenges which are reasoned via pedagogical or technological content knowledge-based arguments. 3D printing was used for producing solutions (e.g. physical models) that support working with found challenges. In chemistry education research, 3D printing has mainly been used for printing research instruments; few studies have investigated its effect on learning or students’ perceptions towards it. There is a great need for comprehensive student-centred pedagogical models for the use of 3D printing in chemistry education.
  • Ahi, Alan A.; Sinkovics, Noemi; Shildibekov, Yelnur; Sinkovics, Rudolf R.; Mehandjiev, Nikolay (2022)
    Advanced digital technologies, such as the Internet of Things, blockchain, big data analytics and augmented reality, are gradually transforming the way multinational firms do business. Due to the extent of this transformation many scholars argue that the integration of these technologies marks the commencement of the fourth industrial revolution (Industry 4.0). However, the question how these advanced technologies impact international business activities needs further attention. To this end, we adopt a multidisciplinary approach to review the related literature in international business (IB), general management, information systems, and operations research. We include the two latter fields, because advanced technologies have received more attention in these bodies of literature. Based on our analysis, we discuss the implications of these technologies for international business. Further, we highlight the drivers of technology utilisation by multinational firms and likely outcomes. We also provide future research avenues.
  • Ajdary, Rubina; Abidnejad, Roozbeh; Lehtonen, Janika; Kuula, Jani; Raussi-Lehto, Eija; Kankuri, Esko; Tardy, Blaise; Rojas, Orlando J. (2022)
    Owing to its purity and exceptional mechanical performance, bacterial nanocellulose (BNC) is well suited for tissue engineering applications. BNC assembles as a network that features similarities with the extracellular matrix (ECM) while exhibiting excellent integrity in the wet state, suitable for suturing and sterilization. The development of complex 3D forms is shown by taking advantage of the aerobic process involved in the biogenesis of BNC at the air/culture medium interphase. Hence, solid supports are used to guide the formation of BNC biofilms that easily form auxetic structures. Such biomaterials are demonstrated as implantable meshes with prescribed opening size and infill density. The measured mechanical strength is easily adjustable (48-456 MPa tensile strength) while ensuring shape stability (>87% shape retention after 100 burst loading/unloading cycles). We further study the cytotoxicity, monocyte/macrophage pro-inflammatory activation, and phenotype to demonstrate the prospective use of BNC as supportive implants with long-term comfort and minimal biomaterial fatigue.
  • Rautamo, Maria M; Kvarnström, Kirsi; Siven, Mia; Airaksinen, Marja; Lahdenne, Pekka Olavi; Sandler, Niklas (2020)
    The utilization of three-dimensional (3D) printing technologies as innovative manufacturing methods for drug products has recently gained growing interest. From a technological viewpoint, proof-of-concept on the performance of different printing methods already exist, followed by visions about future applications in hospital or community pharmacies. The main objective of this study was to investigate the perceptions of healthcare professionals in a tertiary university hospital about oral 3D-printed medicines for pediatric patients by means of focus group discussions. In general, the healthcare professionals considered many positive aspects and opportunities in 3D printing of pharmaceuticals. A precise dose as well as personalized doses and dosage forms were some of the advantages mentioned by the participants. Especially in cases of polypharmacy, incorporating several drug substances into one product to produce a polypill, personalized regarding both the combination of drug substances and the doses, would benefit drug treatments of several medical conditions and would improve adherence to medications. In addition to the positive aspects, concerns and prerequisites for the adoption of 3D printing technologies at hospital settings were also expressed. These perspectives are suggested by the authors to be focus points for future research on personalized 3D-printed drug products.
  • Mendes, Luis; Kangas, Anneli; Kukko, Kirsi; Molgaard, Bjarke; Saamanen, Arto; Kanerva, Tomi; Ituarte, Inigo Flores; Huhtiniemi, Marika; Stockmann-Juvala, Helene; Partanen, Jouni; Hämeri, Kaarle; Eleftheriadis, Konstantinos; Viitanen, Anna-Kaisa (2017)
    3D printers are currently widely available and very popular among the general public. However, the use of these devices may pose health risks to users, attributable to air-quality issues arising from gaseous and particulate emissions in particular. We characterized emissions from a low-end 3D printer based on material extrusion, using the most common polymers: acrylonitrile-butadiene-styrene (ABS) and polylactic acid (PLA). Measurements were carried out in an emission chamber and a conventional room. Particle emission rates were obtained by direct measurement and modeling, whereas the influence of extrusion temperature was also evaluated. ABS was the material with the highest aerosol emission rate. The nanoparticle emission ranged from 3.7.10(8) to 1.4.10(9) particles per second (# s(-1)) in chamber measurements and from 2.0.10(9) to 4.0.10(9) # s(-1)in room measurements, when the recommended extruder temperature was used. Printing with PLA emitted nanoparticles at the rate of 1.0.10(7) # s(-1) inside the chamber and negligible emissions in room experiments. Emission rates were observed to depend strongly on extruder temperature. The particles' mean size ranged from 7.8 to 10.5 nanometers (nm). We also detected a significant emission rate of particles of 1 to 3nm in size during all printing events. The amounts of volatile organic and other gaseous compounds were only traceable and are not expected to pose health risks. Our study suggests that measures preventing human exposure to high nanoparticle concentrations should be adopted when using low-end 3D printers.
  • Kallela, Karla (Helsingin yliopisto, 2021)
    3D printing has been described as a revolutionary technology challenging copyright law to the core. 3D printing essentially enables the fast reproduction of objects and enables transforming digital items into physical ones effortlessly. This thesis examines the copyright status of a computer-aided design (CAD) file, which functions as the blueprint and instructions for a 3D printer. Such a file carries information about the design it contains, and a 3D printer may read these instructions and produce the digital item in physical, three-dimensional form. The core of this thesis is to examine whether a CAD file fits within the scope of application of copyright law and further inspects the repercussions of copyright protection being granted for such files. Moreover, the writer suggests practical interpretations and changes as to how copyright law should be interpreted for the regime to be better adapted to technological change in the future. In this thesis, the writer concludes that based on the Finnish Copyright Act (404/1961) and Directive 2001/29/EC as well as applicable case law developed by the Court of Justice of the European Union (CJEU), there is nothing precluding treating such a file as subject matter which may be protected under the national (and EU) copyright regime. This interpretation is in fact encouraged from the basis of applicable case by the CJEU, such as cases C-5/08 Infopaq, C-355/12 Nintendo, C-310/17 Levola and C‑683/17 Cofemel. For something to constitute protectable subject matter, the focal point is for the expression to be contained with sufficient precision and objectivity and more importantly, that the expression constitutes the intellectual creation of its author. With regard to the repercussions of this protection, it is clear that should a CAD file be protected by way of a copyright, a 3D item produced from such a file should either constitute a reproduction or derivative work of such a file. Further, the writer suggests that in order to provide a clear framework for operators in the field, a position paper similar to the one adopted by the European Communities Trade Mark Association in April 2021 as regards design law and 3D printing should be developed. In addition, it is recommended that rightholders take proactive measures in safeguarding their works by adapting business models so that their authentic products are offered by way of different licensing models to combat piracy, similar to the solution developed in the music industry after peer-to-peer online sharing posed troubles for the industry. In the event of the true mass commercialization of 3DP, a centralized body to monitor the industry should be developed, one that establishes functioning licensing models to benefit rightholders. Finally, the FCA should be interpreted in a truly technologically neutral manner. It is likely that such an interpretation will however not fix all the issues copyright law is posed with, and thus, a cohesive copyright reform may be necessary in the future.
  • Akmal, Jan Sher; Salmi, Mika; Hemming, Björn; Teir, Linus; Suomalainen, Anni; Kortesniemi, Mika; Partanen, Jouni; Lassila, Antti (2020)
    Featured Application Accuracy of additively manufactured implants for clinical surgery. Abstract In craniomaxillofacial surgical procedures, an emerging practice adopts the preoperative virtual planning that uses medical imaging (computed tomography), 3D thresholding (segmentation), 3D modeling (digital design), and additive manufacturing (3D printing) for the procurement of an end-use implant. The objective of this case study was to evaluate the cumulative spatial inaccuracies arising from each step of the process chain when various computed tomography protocols and thresholding values were independently changed. A custom-made quality assurance instrument (Phantom) was used to evaluate the medical imaging error. A sus domesticus (domestic pig) head was analyzed to determine the 3D thresholding error. The 3D modeling error was estimated from the computer-aided design software. Finally, the end-use implant was used to evaluate the additive manufacturing error. The results were verified using accurate measurement instruments and techniques. A worst-case cumulative error of 1.7 mm (3.0%) was estimated for one boundary condition and 2.3 mm (4.1%) for two boundary conditions considering the maximum length (56.9 mm) of the end-use implant. Uncertainty from the clinical imaging to the end-use implant was 0.8 mm (1.4%). This study helps practitioners establish and corroborate surgical practices that are within the bounds of an appropriate accuracy for clinical treatment and restoration.
  • Salmi, Mika; Wolff, Jan; Mäkitie, Antti (2022)
  • Sodupe Ortega, Enrique; Sanz-Garcia, Andres; Pernia-Espinoza, Alpha; Escobedo-Lucea, Carmen (2019)
    Hybrid constructs represent substantial progress in tissue engineering (TE) towards producing implants of a clinically relevant size that recapitulate the structure and multicellular complexity of the native tissue. They are created by interlacing printed scaffolds, sacrificial materials, and cell-laden hydrogels. A suitable biomaterial is a polycaprolactone (PCL); however, due to the higher viscosity of this biopolymer, three-dimensional (3D) printing of PCL is slow, so reducing PCL print times remains a challenge. We investigated parameters, such as nozzle shape and size, carriage speed, and print temperature, to find a tradeoff that speeds up the creation of hybrid constructs of controlled porosity. We performed experiments with conical, cylindrical, and cylindrical shortened nozzles and numerical simulations to infer a more comprehensive understanding of PCL flow rate. We found that conical nozzles are advised as they exhibited the highest shear rate, which increased the flow rate. When working at a low carriage speed, conical nozzles of a small diameter tended to form-flatten filaments and became highly inefficient. However, raising the carriage speed revealed shortcomings because passing specific values created filaments with a heterogeneous diameter. Small nozzles produced scaffolds with thin strands but at long building times. Using large nozzles and a high carriage speed is recommended. Overall, we demonstrated that hybrid constructs with a clinically relevant size could be much more feasible to print when reaching a tradeoff between temperature, nozzle diameter, and speed.
  • Akmal, Jan Sher; Salmi, Mika; Mäkitie, Antti; Björkstrand, Roy; Partanen, Jouni (2018)
    The purpose of this study is to demonstrate the ability of additive manufacturing, also known as 3D printing, to produce effective drug delivery devices and implants that are both identifiable, as well as traceable. Drug delivery devices can potentially be used for drug release in the direct vicinity of target tissues or the selected medication route in a patient-specific manner as required. The identification and traceability of additively manufactured implants can be administered through radiofrequency identification systems. The focus of this study is to explore how embedded medication and sensors can be added in different additive manufacturing processes. The concept is extended to biomaterials with the help of the literature. As a result of this study, a patient-specific drug delivery device can be custom-designed and additively manufactured in the form of an implant that can identify, trace, and dispense a drug to the vicinity of a selected target tissue as a patient-specific function of time for bodily treatment and restoration.
  • Itämö, Satu (Helsingfors universitet, 2018)
    Marketing authorized pharmaceutical preparations that are aimed at adult use cause problems both in administration and when dosing. Over and underdosing are the most common medication errors in pediatric population. Only a fraction of medicinal products are clinically tested and evaluated for pediatric use. Children should have the right for the best achievable health, medical care and rehabilitation. The aim of this study was to determine problematic pharmaceutical preparations, formulations or excipients experienced by healthcare professionals. The another aim of this study was to comprise (?) the view of healthcare professionals about 3D-printed medicinal products by using the collected data. By using the data, the problems, challenges, targets for development and other suggestions regarding pediatric medication were identified. New 3D printed medicines suitable for children can be developed by using the observations of this study. The study was carried out as semi-structured interview. Frameworks of the themes were structured by using the subjects of a recently made semi-structured questionnaire. The semi-structured interview was carried out as a group-interview, where the participants were presented open questions according to the themes structured before. According to the study results, the prejudices of the interviewees towards the new technology were mainly positive. The adjustability of the printed medicine by the means of the patient was most highlighted property in the interviews. Accoring to the experiences of the interviewees’, the most suitable pharmaceutical preparations used are liquid preparations such as oral liquids or suspensions. When using solid oral formulations, the age of the patient was not seen as significant. The most common reason for compounding the preparation was the wrong size of the product or dose. The varying availability of pharmaceutical preparations was seen as delaying factor at the start of the medical treatment. In the interview the pharmacists recognized the most common excipients causing adverse events. The different roles of the occupational groups were identified according to their work duties.
  • Auvinen, Vili-Veli; Virtanen, Juhani; Merivaara, Arto; Virtanen, Valtteri; Laurén, Patrick; Tuukkanen, Sampo; Laaksonen, Timo (2020)
    Nanocellulose hydrogel has been shown to be an excellent platform for drug delivery and it has been lately studied as an injectable drug carrier. 3D printing is an effective method for fast prototyping of pharmaceutical devices with unique shape and cavities enabling new types of controlled release. In this study, we combined the versatility of 3D printing capsules with controlled geometry and the drug release properties of nanocellulose hydrogel to accurately modulate its drug release properties. We first manufactured non-active capsules via 3D printing from biocompatible poly(lactic acid) (PLA) that limit the direction of drug diffusion. As a novel method, the capsules were filled with a drug dispersion composed of model compounds and anionic cellulose nanofiber (CNF) hydrogel. The main benefit of this device is that the release of any CNF-compatible drug can be modulated simply by modulating the inner geometry of the PLA capsule. In the study we optimized the size and shape of the capsules inner cavity and performed drug release tests with common beta blockers metoprolol and nadolol as the model compounds. The results demonstrate that the sustained release profiles provided by the CNF matrix can be accurately modulated via adjusting the geometry of the 3D printed PLA capsule, resulting in adjustable sustained release for the model compounds.
  • Helinko, Orvokki; Irace, Alexandria L.; Suomalainen, Anni; Hagström, Jaana; Mesimäki, Karri (2021)
  • Huotilainen, Eero; Salmi, Mika; Lindahl, Jan (2019)
    Background: The fit of the allograft is a particular concern in fresh cadaveric osteochondral allograft (FOCA) surgery. Digital design and fabrication were utilized in conjunction with traditional surgery to enable efficient discovery and reproduction of appropriately dimensioned allograft. Methods: A patient with large osteochondral defects in the lateral femoral condyle was to undergo FOCA surgery. A digital virtual operation was performed, based on computed tomography (CT) images of the patient. Polyamide saw templates were manufactured using a selective laser sintering process, and gypsum powder was used to manufacture preoperative and intraoperative medical models with binder jetting process. The design dimensions were verified numerically by determining the intactness of the section surface and allograft volume based on four independent measurements of the initial design, and an automated design optimization strategy was postulated. For the surgery, a lateral longitudinal approach was employed. Results: The virtual operation allowed an efficient design of the saw templates. Their shape and dimensions were verified with a numerical CT analysis method. The allograft dimensions (medial-lateral/superior-inferior/anterior-posterior) were approximately 40/28.5/24 mm, respectively, with the anterosuperior corner diagonally removed, yielding a section volume of approximately 16.5 cm(3). These manually chosen dimensions were reminiscent of the corresponding computationally optimized values. Conclusions: Use of computer-aided design in virtual operation planning and three-dimensional printing in the fabrication of designed templates allowed for an efficient FOCA procedure and accurate allograft fitting. The numerical optimization method allowed for a semiautomated design process, which could in turn be realized also with surgical navigation or robotic surgery methods. (C) 2019 Elsevier B.V. All rights reserved.
  • Makitie, A. A.; Salmi, M.; Lindford, A.; Tuomi, J.; Lassus, J. (2016)
    Background and aims: Prosthetic mask restoration of the donor face is essential in current facial transplant protocols. The aim was to develop a new three-dimensional (3D) printing (additive manufacturing; AM) process for the production of a donor face mask that fulfilled the requirements for facial restoration after facial harvest. Materials and methods: A digital image of a single test person's face was obtained in a standardized setting and subjected to three different image processing techniques. These data were used for the 3D modeling and printing of a donor face mask. The process was also tested in a cadaver setting and ultimately used clinically in a donor patient after facial allograft harvest. Results: and Conclusions: All the three developed and tested techniques enabled the 3D printing of a custom-made face mask in a timely manner that is almost an exact replica of the donor patient's face. This technique was successfully used in a facial allotransplantation donor patient. (C) 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
  • Oblom, Heidi; Sjöholm, Erica; Rautamo, Maria; Sandler, Niklas (2019)
    To date, the lack of age-appropriate medicines for many indications results in dose manipulation of commercially available dosage forms, commonly resulting in inaccurate doses. Various printing technologies have recently been explored in the pharmaceutical field due to the flexible and precise nature of the techniques. The aim of this study was, therefore, to compare the currently used method to produce patient-tailored warfarin doses at HUS Pharmacy in Finland with two innovative printing techniques. Dosage forms of various strengths (0.1, 0.5, 1, and 2 mg) were prepared utilizing semisolid extrusion 3D printing, inkjet printing and the established compounding procedure for oral powders in unit dose sachets (OPSs). Orodispersible films (ODFs) drug-loaded with warfarin were prepared by means of printing using hydroxypropylcellulose as a film-forming agent. The OPSs consisted of commercially available warfarin tablets and lactose monohydrate as a filler. The ODFs resulted in thin and flexible films showing acceptable ODF properties. Moreover, the printed ODFs displayed improved drug content compared to the established OPSs. All dosage forms were found to be stable over the one-month stability study and suitable for administration through a naso-gastric tube, thus, enabling administration to all possible patient groups in a hospital ward. This work demonstrates the potential of utilizing printing technologies for the production of on-demand patient-specific doses and further discusses the advantages and limitations of each method.