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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Bioprinting for Bone Regeneration with Nanofiber Coated Tubular Scaffolds

Researchers from both Mexico and Costa Rica have joined efforts to further research into bone regeneration via bioprinting, allowing doctors and surgeons to create patient-specific scaffolds for improved treatment. 3D printing and tissue engineering show great promise for scientists because of the opportunity to build complex geometries, with precision. All the classic benefits of 3D printing are enjoyed during these experiments too, like affordability, speed in production, and best of all—the ability to create on-demand in the lab, manufacturing and making changes to structures in a completely self-sustained fashion.

The team of researchers detail their findings further in ‘Biocompatibility of Developing 3D Printed Tubular Scaffold Coated with Nanofibers for Bone Applications’ explaining how bone scaffolds can be improved further with an added composite layer that creates a layer more conducive to cell attachment and uniform seeding. To create these scaffolds, the team used a unique air jet spinning (AJS) technique, featuring a specialized spinning system nozzle and a surface for collecting polymer fibers and compressed gas—and they also 3D printed tubular scaffolds with PLA, featuring ‘submicrometric fiber surface coating in the biological response of human fetal osteoblast cells (hFOB).’

This new method uses both the inner core of the PLA 3D printing material and the outer layer of its nanofibers, with the researchers using Cura software for internal geometries and a MakerMex 3D printer to manufacture the tubular structures. The dual technique allowed the team to create a fiber layer dispersion resulting in a surface with ‘homogeneous thickness distribution’ and nanofibers adapting well to merging with the 3D printed scaffold. Adhesion was noted as ‘very strong,’ with the composites showing an increase in thermal stability, and the coating imbuing the tubular scaffold with properties critical to tissue engineering for bone regeneration.

SEM micrographs showing the morphology of the 3D-printed tubular scaffold

“The 3D surface of the printed tubular scaffold exhibited distinctive morphologies and structures analyzed by SEM, and the surface roughness of the tubular scaffolds increased with the incorporation of the coating functionalization by the fiber membrane,” concluded the authors.

“Moreover, scaffolds coated with submicrometric fibers allow hFOB cells to adhere and proliferate better than uncoated 3D tubular scaffolds showing that the fibers work as a platform to improve cell biocompatibility (being not toxic to cells) and provide support to colonization and cell growth by the osteoblast cells. Moreover, the 3D tubular scaffold coated with fibers needs more studies as a biomineralization process for it to have a potential future use in bone tissue engineering or for it to have an application in the vascularization process.”

Optical profiler data showing the topography of a 3D-printed tubular scaffold. (a) Images show the uncoated smooth surface and
(b) the coated surface where roughness is strongly enhanced by the presence of nanofibers.

The field of bone regeneration is fraught with challenge, but doctors and surgeons press on to make improvements in both surgical techniques and devices such as implants so that they can improve the quality of life for patients who may be debilitated or in great pain. Researchers have engaged in many different studies over the years regarding 3D printing, producing devices such as implants made just for patients in China, bone scaffolds created at low temperatures, and other different types of bone scaffolding platforms. 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.

SEM micrographs of the 3D-printed tubular scaffold coated with 7% PLA nanofibers.

SEM micrographs of the 3D tubular scaffold surface seeded with hFOB cells showing some cells with an oval to spindle-shaped morphology typical of osteoblasts cells.

[Source / Images: ‘Biocompatibility of Developing 3D Printed Tubular Scaffold Coated with Nanofibers for Bone Applications’]