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Bioprinting Hot Dogs with Hierarchical Structures

Researchers around the world continually surprise us with innovation, but rarely do they reach into the roots of popular culture—and the food that accompanies it—applying it to the world of bioprinting…and with hot dogs in mind, no less. However, that’s exactly what has inspired German and Chinese scientists to build bioprinting structures, with their study outlined in the recently published ‘3D Printing of Hot Dog-Like Biomaterials with Hierarchical Architecture and Distinct Bioactivity.’

Fabrication and morphology of hot dog‐like scaffolds (HD‐AKT). a) The schemata of preparation of HD‐AKT, combining 3D printing and bidirectional freezing to realize 3D printed scaffolds containing rods with aligned lamellar microstructure. b–e) 3D micro‐CT images and f,g) 2D micro‐CT images of HD‐AKT from different views showing the scaffold structure, which is hollow tube macrospores embedded by bioceramic rods with the uniformly aligned lamellar structure of rods.

The researchers fabricated hierarchical structures using direct ink writing (DIW), with the hot dog structure figuring in with the use of tubes:

“The scaffolds are composed of hollow bioceramic tubes (mimicking the “bread” in hot dogs, pore size: ≈1 mm) embedded by bioceramic rods (mimicking the “sausage” in hot dogs, diameter: ≈500 µm) and the sausage‐like bioceramic rods possess uniformly aligned lamellar micropores (lamellar pore size: ≈30 µm),” said the researchers.

While hierarchical structures are often used in bioprinting, it can be challenging to find suitable materials in creating micro/nanostructures, and especially with DIW. And while challenges have continued in implanting 3D printed scaffolds to regenerate bone growth, there has been some success. The researchers contend, however, that hierarchy in structure is needed to promote better tissue growth, with the ‘hot-dog like structure’ lending itself to better cell adhesion and supply of nutrients, with the rods enhancing delivery of osteogenic drugs.

“By mimicking the function of nutrition supply for sausages in hot dog, the potential of the scaffolds for loading icariin (Ica, a model osteogenic drug), was investigated in this study,” explained the researchers.

“However, the Ica loading efficiency and capacity of S‐AKT were much lower than that of HD‐AKT, indicating the excellent loading capacity of the hierarchical hot dog‐like scaffolds. The thermogravimetric analysis further verified the significantly improved loading efficiency of HD‐AKT scaffolds as compared to those without hot dog microstructure.”

Hot dog‐like scaffolds are an excellent carrier for drug and protein. The drug Ica and protein BSA loading and release properties of the HD‐AKT. a) The Ica loading efficiency, and b) the loading capacity of traditional solid struts scaffolds(S‐AKT), H‐AKT, and different kinds of HD‐AKT. c) Thermogravimetric analysis of the scaffolds after loading the Ica. d) The Ica release of different kinds of scaffolds after loading Ica (S‐AKT/Ica, H‐AKT/Ica, HD‐20AKT/Ica, HD‐30AKT/Ica, HD‐40AKT/Ica, and HD‐50AKT/Ica). e) The BSA loading efficiency. f) The BSA release of the scaffolds. g–i) SEM images of the hot dog rod of scaffolds g) after 90 d Ica release. h) Surface images and i) the cross‐section image show lots of mineralized hierarchical structures on the surface of hot dog rod of scaffolds. Compared with the S‐AKT and H‐AKT, the HD‐AKT have higher loading efficiency and capacity. Meantime, HD‐AKT possess longer Ica/BSA release time.

The research team also discovered that other drugs could be distributed too, such as the large molecule protein bull serum albumin (BSA). Even more encouraging, the researchers found that the scaffolds exhibited ‘excellent bioactivity,’ proven through in vivo processes for bone regeneration as they implanted drugs into ‘rabbit femoral defects’ for eight weeks with no inflammation, and proof of bone tissue growth.

Hot dog‐like scaffolds are an excellent platform for cell delivery and differentiation. The proliferation, morphology, and relative genes expression of rBMSCs cultured on different scaffolds. a‐d) Confocal and SEM images of rBMSCs cultured on a) S‐AKT, b) H‐AKT, c) HD‐30AKT, and d) HD‐30AKT/Ica. e) The rBMSCs (red color) adhesion on the rod of HD‐AKT. f) The proliferation of rBMSCs after seeding in different kinds of scaffolds, showing hot dog‐like scaffolds are beneficial for cell proliferation. g) The relative osteogenic genes expression (OCN, Runx2, OPN, and ALP) of rBMSCs in scaffolds, indicating that the Ica release from the scaffolds promotes the relative osteogenic genes expression of rBMSCs (n = 6, *P < 0.05, and **P < 0.01.).

“Our study suggests that the hot dog‐like scaffolds can be used for the multifunctional biomaterials for drug delivery, tissue engineering, and regenerative medicine. The combined strategy of DIW 3D printing with bidirectional freezing is a promising method to prepare biomimetic and hierarchical biomaterials,” concluded the researchers.

Hot dog‐like scaffolds possess excellent bone‐forming bioactivity after implanted in the femoral defects of rabbits. The characterizations of hot dog‐like scaffolds for osteogenesis in vivo. a1–d1) Digital, a2–d2) 2D micro‐CT, and 3D micro‐CT images (a3–d3: transverse view, and a4–d4: sagittal view) of the defects at week 8. In 3D micro‐CT images, green, red and white represents new bone, scaffold, and primary bone, respectively. e) Micro‐CT reconstruction analysis exhibits the volume ratio of the new bone to the original defect regions (BV/TV) at week 8. HD‐30AKT and HD‐30AKT/Ica indicate significantly. f) The newly formed bones (red) grow into the lamellar microstructures (green arrows) of hot dog‐like scaffold. g–j) Hard histological sections stained with Van Gieson’s picrofuchsin of g) Blank, h) H‐AKT, i) HD‐AKT, and j) HD‐AKT/Ica, red color stands newly formed bone and black color represents scaffolds. Newly formed bone can grow into the hierarchical rods of the scaffolds (blue circle point to the new bone in the hierarchical rods). improvement in new bone regeneration as compared to Blank control. In addition, Ica can also promote osteogenesis, suggesting that both hierarchical structure and the Ica delivery of the hot dog‐like scaffolds contribute to the bone regeneration (n = 6, *P < 0.05, **P < 0.01, and ***P < 0.001.).

While man-made processed foods are certainly inspiring to many, undoubtedly nature continues to propel scientists and designers forward from creating conductive parts to custom-made shoes, and liquid polymers for 3D printing. 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.

[Source / Images: ‘3D Printing of Hot Dog-Like Biomaterials with Hierarchical Architecture and Distinct Bioactivity’]

 

 

 

 

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SUTD researchers integrate functional components to 3D printed microfluidic devices

Singapore University of Technology and Design‘s (SUTD) Soft Fluidics Lab has developed a simple method to 3D print microfluidic devices integrated with fluid handling and functional components. The lab’s direct ink writing 3D printer dispenses a fast-curing flexible silicone resin on various substrates to form microchannels. Microchannels fabricated by SUTD have tunable dimensions and a […]
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UV Assisted Direct Ink Writing of 3D Printed and “4D Printed” Shape Memory Epoxy Parts

The magic of 3D printing has touched most of us in some way by now, as schools in many countries are establishing programs, libraries offer makerspaces for patrons, and designers like architects show us their often bold new 3D printed works made possible by accessible new technology. Some researchers, designers, and engineers not only envision the next step, however, but have already made strides in 4D innovation—characterized by parts that are not only highly functional but may be smart enough to morph into different shapes or textured on an as-needed basis.

Researchers from both Southwest Jiaotong University and Georgia Institute of Technology discuss their findings on exploring both 3D and 4D printing via UV-assisted direct-ink write printing. While noting that traditional 3D printing processes make use of typical materials like ABS, PLA, and more, the researchers looked toward epoxy for more expansive uses which may require coating and adhesives. Epoxy is also known for being mechanically strong, and more resistant in the face of temperature and chemicals—qualities that make it suitable for applications like aerospace.

Previously epoxy has presented challenges with strain break and affordability, but 3D printing with direct ink writing capability has been more successful with the use of nanoparticles that add a ‘shear-thinning effect.’ The thermal curing process can be an issue though if not performed at lower temperatures, and with close control and monitoring.

High temperatures may lead to warping of the printed object, though, and this alternative preparation of ingredients for the direct-writing ink has been considered ‘tedious,’ according to previous researchers. Others have developed DIW processes with UV curing. It was successful in applications for creating items such as conductive spring coils and freestanding nanocomposite strain sensors, but there were still significant challenges such as clogging, brittleness, and printed parameter issues.

The research team created a new method, still relying on UV-assistance for curing, but in two stages:

“A new resin containing rapid photocurable resin and thermally curable epoxy oligomer is reinforced with fumed SiO2, which can be utilized as ink for DIW printing,” state the researchers. “Each layer is printed followed by ex situ UV curing, which can efficiently avoid nozzle clogging. The flexible network formed by the UV curable resin can hold the shape of the part very well even at an elevated temperature.”

“After DIW printing, the part with the complex structure is moved into a heating oven and thermally cured similar to conventional epoxy resin. Moreover, good interfacial bonding can be achieved by forming chemical bonds between different filaments leading to isotropic mechanical properties. This two-stage curing process enables the fabrication of interpenetrating polymer network (IPN) epoxy composites, which show high toughness with tunable mechanical properties. The printed epoxy composite also shows a good shape memory effect with a high shape fixity ratio, shape recovery ratio, and cycling stability.”

Schematic illustration of the 3D printing epoxy composite material

With the new DIW method, they printed:

The researchers state that lower speed is an issue with this technique, but other benefits make up for that, such as ‘excellent interfacial bonding’ of materials and ‘widely tunable mechanical properties’ that are apparent in the post-curing stage. In 3D printing with epoxy composites, one layer of material was deposited with DIW, and then it was UV cured for ten seconds. This is repeated for each layer, allowing for printing of parts with complex geometries, later cured for two hours and post-cured for one hour.

“After that, the epoxy oligomer in the first network was polymerized to form an IPN with highly enhanced mechanical properties,” state the researchers.

Photographs and SEM images of the 3D printing with photo and thermal cure results of epoxy composites. The photos above the dashed line show the printed structures with the photo cure, and the photos under the dashed lines show the structures with two-stage cures (photo cure and subsequent thermal cure). (a) Square-shaped lattice structure; (b) gear wheel; (c) spiral swirl bowl; (d) 3-links trophy; (scale bars in a–d are 6 mm); (e) lattice structure with a single-layered wall and its enlarged SEM images.

The nanocomposite ink, measured with a viscometer, began to exhibit shear-thinning behavior as silica was added, allowing for successful extrusion. In testing, the team created numerous complex structures with a 22 GA nozzle (0.41 mm inner diameter). Not only was 3D printing with their ink sufficient, but they deemed the results to be excellent. Along with this, they began 3D printing with a focus on shape memory, testing their efforts on a 3D printed logo that responded within ten seconds after being immersed in a hot oil bath. Results were the same with a printed test strip also.

With a wide choice of UV-curable resin, thermal curing resin and nanoparticles, this UV-assisted DIW 3D printing via a two-stage curing method can broaden the implementation of 3D printing to directly fabricate thermosetting materials with tunable and enhanced properties for high performance and functional applications,” concluded the researchers. If commercialized this kind of a process would have a broad range of applications in light-based applications.

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.

[Source / Images: ‘Fabrication of Tough Epoxy with Shape Memory Effects by UV-assisted Direct-ink Write Printing’]

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Virginia Tech Researchers 3D Print Kapton Using Direct Ink Writing

Daniel Rau works with a 3D printer in the DREAMS Lab.

Last year, a group of Virginia Tech researchers developed a method for 3D printing Kapton, a foil-like polyimide that possesses excellent thermal and chemical stability and therefore is commonly used in insulation for aerospace applications. It also acts as an electrical insulator and is resistant to ultraviolet radiation. It doesn’t dissolve in solvents and has a degradation temperature of about 550°C.

“(Kapton) can withstand all kinds of harsh environmental insults: radiation, high temperature, chemical reagents,” said Timothy Long, a professor of chemistry and the director of Virginia Tech’s Macromolecules Innovation Institute (MII). “It’s one of these molecules that is the ultimate in terms of performance.”

Prior to last year’s study, Kapton was only available in thin two-dimensional sheets, like tape or the “gold foil” that wraps around satellites to insulate them, but the researchers then figured out how to 3D print the material using SLA. Now they have developed a second method for 3D printing Kapton: direct ink writing, or DIW. They detailed their research in a recent paper entitled “Ultraviolet-Assisted Direct Ink Write to Additively Manufacture All-Aromatic Polyimides.“

“If you think of caulking a bathtub or decorating a cake with icing, (DIW is) a very similar process,” said Daniel Rau, one of the co-authors and a Ph.D. student in the Design, Research, and Education for Additive Manufacturing Systems (DREAMS) Lab in the Department of Mechanical Engineering. “Because it’s so simple, (DIW) gives us incredible flexibility on the ink, synthesis, and the properties it has.”

After 3D printing the material using direct ink writing, the printed parts had similar properties to commercially available Kapton film. They had similar mechanical properties up to 400°C, and their degradation temperature was 534°C. According to Rau, while SLA is better for 3D printing entire objects, direct ink writing is better for 3D printing different materials side by side.

“All of the different additive manufacturing processes are like different tools in the workshop,” Rau said. “You have hammers and that has its strengths. You have saws and that has its strengths.”

In addition to multi-material 3D printing, the researchers can also now print Kapton directly onto an existing material using direct ink writing, said Christopher Williams, director of the DREAMS Lab and associate director of MII. They can also print the material on curved surfaces.

“As soon as we were able to print Kapton, people asked us about applications,” Williams said. “The answer we often gave was printed electronics, but that’s challenging to do in stereolithography. This new technique could really enable that as we look towards simultaneous printing of conductive materials and this excellent insulator.”

In last year’s study on SLA 3D printing, Jana Herzberger, a postdoctoral student in the Long Group, created a precursor polymer to Kapton in liquid form. The liquid wouldn’t work for direct ink writing because it wouldn’t hold its shape after extrusion. Instead, Herzberger created a resin with a consistency similar to peanut butter.

“When Dr. Williams challenged us to modify the resin for the direct ink write process, we all thought it would be rather straightforward,” Herzberger said. “It turned out that the ‘easy’ route didn’t work, and we had to make some modifications to the original resin. Often times, I synthesized a resin and studied its rheological properties [rheology is the study of how a matter flows or moves in the presence of deformation], and Danny tested if it performed in the printer as we predicted. It was a new experience for me to work with engineers, and I think we learned a lot from each other and improved our communication skills quite a bit.”

Herzberger and Rau both worked on finding the right balance of an ink that she could synthesize and he could print.

“We both had to meet in the middle and make concessions and communicate,” Rau said. “This was a great partnership — an iterative process — to make this ink printable. Neither of us had the knowledge to go from material creation to final part.”

Long’s and Williams’ groups worked closely together as well to create the new method.

“My group makes macromolecules and Chris’ group puts them into unique geometric shapes,” Long said. “It’s almost like one group working together to solve really complex questions like this.”

Discuss this and other 3D printing topics at 3DPrintBoard.com or share your thoughts below. 

[Source/Images: Virginia Tech]