Finland Archives - Perfect 3D Printing Filament

Finland is one of Europe’s most forested nations. Over 70 percent of the country’s boreal forest is covered with spruce, pine, downy birch, and silver birch. But beyond the splendor of the Finnish woodlands, all these trees have one thing in common, and that is nanocellulose. A light solid substance obtained from plant matter which comprises cellulose nanofibrils (CNF) and is considered a pseudo-plastic that possesses the property of specific kinds of gels that are generally thick in normal conditions. Overall, it is a very environmentally friendly and non-toxic substance that is compatible with the human body and has the potential to be used for a range of medical applications.

In 2018, the Department of Bioproducts and Biosystems at Aalto University, located just outside Helsinki, began searching for new ideas to revitalize one of the country’s traditional economic engines, forests (which are handled sustainably thanks to renewable forest resources). At the time, they noticed that one of the possible applications could be working with nanocellulose. Forward two years and the researchers have come up with a new bioink formulation praising nanocellulose at its basis.

Thanks to the structural similarity to extracellular matrices and excellent biocompatibility of supporting crucial cellular activities, nanocellulose-based bioprinting has clearly emerged for its potential in tissue engineering and regenerative medicine. The qualities of the generally thick and fluid light substance make it an excellent match to develop bioinks that are both suitable and scalable in their production, but also have consistent properties. However, there have been major challenges in processing nanocellulose.

As described by Aalto University researchers in a recently published paper in the science journal ACS Publication, the unresolved challenges of bioink formulations based on nanocelluloses are what stops the substance from becoming one of the preferred components for 3D bioprinting structures. This is why Finnish researchers focused on developing a single-component bioink that could be used to create scaffolds with potential applications in cardiac biomedical devices, while fundamentally dealing with some of the limitations of using nanocellulose-based bioinks.

A co-author of the paper and a doctoral candidate at Aalto’s Department of Bioproducts and Biosystems, Rubina Ajdary, told 3DPrint.com that “other than natural abundance and as a renewable resource, nanocellulose has demonstrated to have an outstanding performance in tissue engineering.” She also suggested that “recent efforts usually consider the use of nanocellulose in combination with other biopolymers, for example, in multicomponent ink formulations or to encapsulate nanoparticles. But we were interested in investigating the potential of monocomponent nanocellulose 3D printed scaffolds that did not require crosslinking to develop the strength or solidity.”

In fact, the Biobased Colloids and Materials (BiCMat) research group at Aalto University, led by Orlando Rojas, proposed heterogeneous acetylation of wood fibers to ease their deconstruction into acetylated nanocellulose (AceCNF). As a unique biomaterial opportunity in 3D scaffold applications, the team considered using nanocelluloses due to the natural, easy to sterilize, and high stability porosity of the substance, and chose to introduce AceCNF for the generation of 3D printed scaffolds for implantation in the human body. The team then went on to evaluate the interactions of the scaffolds with cardiac myoblast cells.

“Most modifications make the hydrogels susceptible to dimensional instability after 3D printing, for instance, upon drying or wetting. This is exacerbated if the inks are highly diluted, which is typical of nanocellulose suspensions, forming gels at low concentrations,” went on Ajdary. “This instability is one of the main reasons why nanocellulose is mainly combined with other compounds. Instead, in this research, we propose heterogeneous acetylation of wood fibers to ease their deconstruction into acetylated nanocellulose for direct ink writing. A higher surface charge of acetylated nanocellulose, compared to native nanocellulose, reduces aggregation and favors the retention of the structure after extrusion even in significantly less concentration.”

This is exactly why it was important for the researches to develop a single component bioink. Nanocellulose has shown promises when combined with other biopolymers and particles. However, Ajdary insists that benefits including similarity to the extracellular matrix, high porosity, high swelling capacity, ease of surface modification, and shear thinning behavior of cellulose, encouraged them to study the potential of monocomponent surface-modified nanocelluloses.

Acetylated nanocellulose (Credit: Aalto University School of Chemical Engineering)

The team at Aalto University used the sustainable and widely available nanocelluloses to make several formulations of bioinks and evaluate them, including unmodified nanocellulose CNF, Acetylated CNF (AceCNF), and TEMPO-oxidized CNF.

To 3D bioprint the hydrogels, researchers used Cellink bioprinters, something Ajdary attributed to the user-friendliness of the device and because it provided a lot of flexibility to test different types of hydrogels and emulsions produced in the research group.

In this new process, the single-component nanocellulose inks were first 3D printed into scaffolds using Cellink’s BIO X bioprinter, which is equipped with a pneumatic print head was used to extrude single filaments and form the 3D structures. Then freeze-dried to avoid extensive shrinkage, and sterilized under UV light. After sterilization the scaffold was ready and cells seeded on the samples.

“3D structures of acetylated nanocellulose are highly stable after extrusion in far less concentrations. The lower concentration in wet condition facilitates the scaffold with higher porosity after dehydration which can improve the cell penetration in the structure and assist in nutrient transport to the cells as well as in the transport of metabolic waste,” specified Ajdary.

The researchers claim that the method was successful as the 3D printed scaffolds were compatible with the cardiomyoblast cells, enabling their proliferation and attachment, and revealing that the constructs are not toxic. Although still in research stages, these bioinks and technique can be used for the inexpensive, consistent fabrication and storage of constructs that can be applied as base materials for cardiac regeneration.

What is novel in this study is the particular focus on single-component nanocellulose-based bioinks that open up a possibility for the reliable and scale-up fabrication of scaffolds appropriate for studies on cellular processes and for tissue engineering. Since this is an ongoing research, we can expect to read more published material from Aalto University researchers as they continue testing their unique technique even further.

Scaffolds corresponding to 3D printed AceCNF (Credit: Aalto University)

The post Aalto University Develops a Novel Bioink for Cardiac Tissue Applications appeared first on 3DPrint.com | The Voice of 3D Printing / Additive Manufacturing.

Finnish researchers reach further into the potential of 3D printed medications, outlining their findings in the recently published ‘Towards Printed Pediatric Medicines in Hospital Pharmacies: Comparison of 2D and 3D Printed Orodispersible Warfarin Films with Conventional Oral Powders in Unit Dose Sachets.’

Researchers continue to seek ways to prevent error in the dispensing of medications, along with offering more patient-specific, on-demand services in healthcare—with an even further sense of urgency to find better ways to treat children. In this study, the scientific team compared traditional techniques in preparing doses of warfarin—a commonly used blood thinner—at HUS Pharmacy in Finland with two new methods for dealing with pediatric dosage.

Experimenting with both semisolid extrusion 3D printing and inkjet printing, the researchers created samples of orodispersible films (ODFs) for a range of prescription strengths, at 0.1, 0.5, 1, and 2 mg.

Treating children can be challenging due to the obvious differences in size and weight, and the seriousness of an overdose. The dosages presented for the study are meant for infants aged 6 to 23 months and preschool children aged 2 to 6 years, with the ODFs composed of thin films that disintegrate quickly upon sticking to the tongue, with no water required. This is one benefit to making medication more enticing to kids, but aesthetic preferences are a considering too—especially for children—in terms of color, size, and taste.

“The different sizes for the EXT ODFs were designed to increase in volume in the same ratio as the dose escalation in order to enable the use of the same printing solution for manufacturing of all sizes. The final sizes of the IJP ODFs were designed to be equal to the sizes designed for the EXT,” stated the researchers.

Designed geometries for the ODFs

The team used a Biobots 1 printer to fabricate both placebo and drug-loaded ODFs, with films created on transparent sheets. The films were printed in three different batches, evaluated daily. For inkjet printing, the team used a PixDro LP50 piezoelectric printer with 128 nozzles, and a camera to monitor the jetted droplets.

“One printing run resulted in 32 printed films of a certain size that were allowed to dry in ambient conditions overnight and subsequently cut with a scalpel according to a template in order to obtain the final size,” stated the researchers.

Individual sachets were created, weighing 200 mg each, with three batches per dose size produced over three days. Drug concentration depended on the ‘wet weight’ of printed placebos and target doses. The samples and dosages were weighed after EXT printing, offering QA methods that could be used in a hospital setting.

“One discovered drawback with the used EXT printer was that it was difficult to attain the set pressure and even during printing of a single ODF the pressure would typically fluctuate. As pressure is one of the most important parameters to determine how much material is deposited per unit time, it may result in ODFs with fluctuating drug amount,” discussed the researchers. “Other factors to consider when using an EXT 3D printer is that the distance between the syringe tip and the build platform will have an impact on the amount of solution that is being deposited. Furthermore, the length of the tip and the amount of solution in the syringe was seen to influence the pressure required and the amount of solution being deposited. Consequently, at least all of these factors should be standardized or monitored to achieve ODFs with similar properties.”

IJP ODFs were also created in three steps using a modified, high concentration ink, with target doses created in a single layer.

“To achieve the target dose by printing a single layer, the dpi was calculated as described in the methods section,” explained the researchers. “No clogging of the nozzles was observed during printing with the described ink formulation, even though recrystallization during printing of high concentration inks containing solvents that are easily evaporated may be of concern for IJP.”

Manufacturing times for EXT ODFs and IJP ODFs. The manufacturing time includes the actual printing time, not premanufacturing steps nor drying times of films. For inkjet printing 51 ± 9 nozzles were used for target doses 0.1, 0.5, and 1 mg and 45 ± 7 nozzles for a target dose of 2 mg.

All the prepared ODF samples possessed suitable mechanical properties and were ‘superior’ in comparison to traditionally made counterparts, in terms of uniformity, leaving the research team confident about the possibility of printing them in a hospital, fabricating patient-specific doses.

(A) EXT drug-loaded ODF imprinted with a QR code containing information about the dosage form and (B) the same EXT ODF rolled up to visualize the flexibility of the film. (C) IJP drug-loaded ODF with a printed QR code and (D) the flexible ODF is subsequently coiled up for illustrative purposes.

“This study, among other recent studies in the field, have shown the feasibility and potential of using printing techniques for manufacturing of flexible doses, contributing to safer and improved treatments for various patient groups in the future,” concluded the researchers. “In order to produce personalized on-demand dosage forms for children in a hospital pharmacy setting, special attention should be paid to the safety of used excipients, implementation of suitable non-destructive and fast quality assurance methods. Furthermore, the possibility to use disposable parts instead of time-consuming cleaning procedures and short turnaround time for the complete manufacturing process including printing solution preparation and drying time of final dosage form should be ensured in order to successfully implement printing methods as a part of the manufacturing techniques used in a hospital pharmacy.”

Stability of the manufactured dosage forms with a target dose of 2 mg at time points 1, 7, 14, 21, and 28 days. The gray columns represent the target dose of 2 mg. Data shown as average ± SD, n = 10.

As 3D printing continues to make countless impacts in the medical field, medication is definitely an area where there will be long-lasting changes, from creating accelerated doses to DIY drugs and medication dispensers.

What do you think of this news? Let us know your thoughts! Join the discussion of this and other 3D printing topics at 3DPrintBoard.com.

Pictures of the prepared dosage forms: (A) EXT ODFs; (B) IJP ODFs; (C) oral powder; and (D) OPS.

[Source / Images: ‘Towards Printed Pediatric Medicines in Hospital Pharmacies: Comparison of 2D and 3D Printed Orodispersible Warfarin Films with Conventional Oral Powders in Unit Dose Sachets’]

The post Finland: 3D Printing Patient-Specific Doses of Warfarin for Children appeared first on 3DPrint.com | The Voice of 3D Printing / Additive Manufacturing.