Hydrogel 3d printer


3D printing of hydrogel composite systems: Recent advances in technology for tissue engineering

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3D printing of high-strength chitosan hydrogel scaffolds without any organic solvents

Luyu Zhou, ‡ab   Hamed Ramezani,‡ab   Miao Sun,c   Mingjun Xie,ab   Jing Nie,ab   Shang Lv,ab   Jie Cai, d   Jianzhong Fu*ab  and  Yong He *ab  

Author affiliations

* Corresponding authors

a State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou 310027, China
E-mail: fjz@zju. edu.cn, [email protected]

b Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou 310027, China

c Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China

d College of Chemistry & Molecular Sciences, Wuhan University, Wuhan 430072, China

Abstract

3D printing of chitosan hydrogels has attracted wide interest because of their excellent biocompatibility, antibacterial activities, biodegradability, zero toxicity and low cost. However, chitosan inks are often involved in toxic and organic solvents. Moreover, the recently reported 3D-printed chitosan scaffolds lack enough strength, thus limiting their use in tissue engineering. Here, we reported a chitosan ink obtained by dissolving chitosan into an alkali aqueous solution. This chitosan ink is a stable solution at low temperature (5 °C), but once heated, the chitosan chains self-assemble to lead to gelation. Based on this principle, a corresponding direct ink writing (DIW) method was developed to print high-strength chitosan hydrogels. Specifically, the chitosan ink was extruded into heated deionized water to complete the in situ gelation. The temperature of the nozzle and hot water was well controlled to keep the printing process stable. The rheological behavior of the chitosan ink was investigated and the printing parameters were systematically studied to print chitosan hydrogel scaffolds with high quality and high strength. Based on these, high-strength (2.31 MPa for compressive strength) and complex chitosan hydrogel structures can be directly printed. The cell culture and the wound healing results further show that the printed chitosan scaffolds with this method have great potential in tissue engineering.

hybrid hydrogel and extrusion 3D printing / Sudo Null IT News For a long time, 3D printers were used exclusively for the production of functional or aesthetic prototypes, and the technology itself was called "rapid prototyping". The rapid development of computing technology has led to the emergence of various methods for implementing additive technologies: from laser stereolithography (SLA) to the more famous 3D printing (3DP). Another term that appeared as early as 1894, this is a hydrogel - a polymer capable of absorbing water (if very exaggerated). Hydrogels, like additive technologies, have many applications: medicine, pharmacology, and even energy.

So scientists from the University of North Carolina decided to combine 3D printing and hydrogel to create hydrogel structures with the desired properties. There was news about this development on Habré, but we will try to dig deeper. What does the hydrogel under study consist of, what properties can it be endowed with, and what can be made of it? We will find answers to these questions in the report of scientists. Go. nine0003

Research basis

To begin with, it is worth briefly explaining what a hydrogel is. This is a network of intersecting polymer chains capable of equilibrium and reversible swelling in water and aqueous solutions. The basis of the hydrogel are hydrophilic molecules.

The problem with classical hydrogels made from polymer networks in water is that they are soft and brittle; they lack elasticity and strength. Because of this, the use of hydrogels in various industries (robotics, tissue engineering, etc.) is severely limited. nine0003

The elasticity of hydrogel materials can be improved by combining interpenetrating covalent and ionic polymer networks to form highly extensible and strong structures. Another method for improving the mechanical properties of hydrogels is based on the use of fillers with a high aspect ratio (high ratio of the length of the filler to the diameter of its cross section). This allows the gel matrix to be mechanically strengthened. However, the use of a filler material other than the matrix material results in stresses on the interface surfaces that cause cracking when deformed or heated. nine0003

The opposite method is based on the use of single-polymer composites or so-called homocomposites. The mesoscale amplifying network of homocomposites is made from a material that is chemically identical to the primary matrix material. Networks of homocomposite reinforcement make it possible to modulate the mechanical properties of the primary (main) matrix without stress, delamination points, etc. It sounds very promising, but there is also a problem - the manufacture of HHG (from homocomposite hydrogel , i.e. homocomposite hydrogel) is an extremely difficult process due to the lack of methods for creating reinforcing networks with the same chemical composition as the hydrogel matrix. nine0003

In the work we are considering today, scientists describe a new type of HHG, in which both the primary gel matrix and the reinforcing network consist of sodium alginate (SA from sodium alginate ; C 6 H 9 NaO 7 ). These HHGs are reinforced with a fibrillar network of alginate soft dendritic colloids (SDC from soft dendritic colloid ). SDC is a hierarchically structured class of soft matter synthesized through a shear-induced deposition process in a turbulent medium. nine0003

The high degree of branching around the cores of SDC particles makes them morphologically similar to polymeric molecular dendrimers. However, SDCs are much larger than these dendrimers. Scientists believe that hierarchically branched SDCs could be an excellent option for effective reinforcement of composite materials. Significantly, the SDC branches cover a larger surface area, which can increase the stability of the composite by distributing the load more evenly.

Study results

The first step was to prepare soft alginate dendritic colloids (i.e. SDC) to serve as reinforcing meshes. For this, turbulent settling was used. To obtain an SDC hydrogel, an alginate solution (120–190 kDa) was introduced into an aqueous solution of Ca 2+ ions, which efficiently bind two -COO- side groups on the alginate backbone ().


Image #1

The precipitation process leads to the formation of SDC with a characteristic hierarchical morphology ( 1b ) with branching of different scale and generations (secondary branches) of fibers. In fact, SDCs are made up of micron-sized fibers that fork repeatedly into ever finer fibers. The outermost layer ("crown") surrounding each SDC is made up of flexible nanofibers that can be up to 10 nm thick ( 1b ). The nanofibers in the coronas endow them with physical adhesion, which is a major factor in the ability of dendricolloids to create the structural strength of the colloidal network. The final size of conventional SDCs, including their corona, is in the range of 100–500 µm. nine0003

Next, the viscoelastic properties of aqueous SDC suspensions had to be evaluated. First, the scientists tested whether alginate SDC hydrogels form a colloidal network at low volume fractions in water. In theory, in aqueous suspensions, contacting SDCs will adhere strongly due to van der Waals forces to form a percolation* network of branched fiber subcontacts ( 2a ).

Percolation* - in chemistry, the phenomenon of the flow or non-flow of liquids through porous materials. nine0056

Image #2

Evaluation of the storage moduli (G') and loss (G″) of SDC suspensions in the linear viscoelastic region showed that SDCs have a strong tendency to form colloidal networks.

Dynamic modulus* : the dynamic modulus G set can be used to represent the relationship between vibrational voltage and load: G' is the accumulation module; G″ is the loss modulus. nine0003

Yield strength was observed in aqueous suspensions of 0.25 wt% SDC, i.e. at a lower concentration than most types of conventional colloidal gels.

A suspension of 1.0 wt.% SDC showed a G' value of 200 Pa, while the reported value for 1.0 wt.% alginate microgels should be 10–100 Pa. Those. SDC slurries have more pronounced solid-like characteristics than conventional alginate particle slurries.

Continuous phase HHG consists of molecular alginate gel combined with Ca 9 ions0033 2+ . First of all, the scientists analyzed the properties of molecular hydrogels containing 1.0 wt.% bound alginate, but without SDC. The hydrogel was prepared by adding CaCO 3 nanoparticles and D-gluconic acid δ-lactone (GDL) to the SA solution. As GDL undergoes hydrolysis and lowers pH, CaCO 3 slowly releases Ca 2+ ions. After 2 hours of equilibration, data were obtained regarding the viscoelastic properties of the hydrogel ( 2c ). At a concentration of CaCO 3 above 0.05 wt.% the hydrogel behaved like a solid. With further introduction of Ca 2+ into the hydrogel, its rigidity continued to increase. But at CaCO 3 above 0.2 wt.%, syneresis (structure aging) of the hydrogel was observed, followed by water release. As a result, it was found that to maintain the stability of the hydrogel, its composition should contain 1.0 wt.% SA and 0.1 wt.% CaCO 3 .

As a result, the researchers had two components on hand that required combining - SA SDC (alginate soft dendritic colloids) and SA CMH molecular matrix (alginate gel bound by Ca 9 ions0033 2+ ).

A variety of hybrid HHGs have been synthesized where the total SA concentration is kept constant at 1 wt% and the ratio of SDC to CMH is varied.


Image #3

All samples obtained in this way exhibited solids characteristics ( 3a ). The characteristic stress-strain curves ( 3b ) obtained from the mechanical tensile test also demonstrate that hybrid HHGs are more stiff than SDC or CMH gels alone. On chart 3c shows tensile-strain and rheometry measurements for all specimens. Analysis of these data shows that homocomposite systems containing mixed SDC and CMH exhibit a strong synergistic effect. The complex modulus (G) and Young's modulus (E) values ​​for the homocomposite gels showed a threefold increase with maxima at low SDC to CMH ratios.

However, this cannot be attributed solely to the increase in the concentration of Ca 2+ in the homocomposite system. So the maximum shear modulus in HHG (G = 950 Pa at 0.125 wt. % SDC / 0.875 wt.

Therefore, a strong synergistic effect leading to an increase in the mechanical strength of HHG can be directly related to the physical interweaving of molecular SA and colloidal networks of SDC ( 3d ). The resulting structure is stable in most environments, but can be easily destroyed by placing it in solutions of strong chelating agents such as EDTA (ethylenediaminetetraacetic acid; C 10 H 16 N 2 O 8 ).

Scientists note that another important feature of the developed hybrid hydrogel is the ability to change the kinetics of its gelation depending on.

First, the dependence of gelation on time was tested for three variants of samples: SDC, CMH and composite HHG (the SA concentration was the same for all - 1 wt.%).


Picture #4

On the graph 4a presents the results of the analysis of a pure suspension of SDC. It can be seen that SDC immediately exhibits a solid behavior without the addition of CaCO 3 or GDL. This is explained by the fact that the formation of this network occurs due to contact splitting and interweaving of fibrillar dendricolloids.

On the other hand, pure CMH exhibits liquid behavior at first and gradually solidifies as the bonding agent Ca 2+ is released by hydrolysis. The CMH becomes a fully connected structure after 120 minutes ( 4b ).

It is important to note that the time dependent evolution of HHG is directly dependent on the kinetics with which SDC and CMH (the main building blocks of HHG) are assembled in the network. HHG initially solidifies due to gelation of the mechanically rigid SDC network. A stronger hydrogel then forms as the interpenetrating CMH molecular network becomes bound by Ca 2+ ions ( 4c and 4d ).

These material properties show controlled initial yield stresses and a slow increase in hydrogel elasticity over time. Therefore, such a material can be used in 3D printing, which the scientists decided to test at the next stage of the study. nine0003

The fact that the created hydrogel is a homocomposite system allows precise control of its properties. Due to this, such a hydrogel can be used in 3D printing using extrusion, which was previously an extremely difficult task. For example, both SDC and CMH are not extrudable in their pure form, unlike hybrid HHG.

The ability to control the properties of the hydrogel allows the creation of an extrusion "ink" in which the time-independent yield strength and setting time can be adjusted to suit the individual. nine0003

Synergistic effect in mixed SA-SDC composites.

Because the 3D printer applies a pressure drop that exceeds the HHG yield strength, the extruded shape is maintained by the rapid gelation of the SDC network ( 4c , video above).


Image No. 5

It is also important that the developed hydrogel could be used for printing under normal conditions without additional processing or preparation of the material ( ). It is noteworthy that the G' of a pure SDC suspension (1500 Pa) is almost four orders of magnitude greater than that of the CMH mixture before the addition of GDL (0.5 Pa; 5b ).

Despite maximum HHG gel stiffness occurring at lower SDC/CMH ratios ( 4c ), HHG with higher SDC ratios produced more filaments with improved layering (video below).

3D printing of a multilayer structure by extrusion.

for 5a and 5c show the process of 3D printing a homocomposite hydrogel by direct extrusion. HHG is extruded through a nozzle (25 G, inner diameter 0.26 mm) at 140 kPa and the gel retains its shape due to its yield strength (≈80 Pa). Additional structuring in the z-direction can be achieved by stacking successive layers that have been found to adhere well to the underlying ones. The scientists were able to additively print more than 10 layers of hydrogel in the vertical direction without reducing the extrusion speed. After curing (60 minutes), the finished printed structure could be easily removed from the substrate ( 5d ). If there is a need for a structure of large dimensions, then staged extrusion is necessary, giving additional time for the gel to solidify, it is also necessary to increase the yield strength of the material by changing the composition of HHG.

For a more detailed acquaintance with the nuances of the study, I recommend looking at the report of scientists and additional materials to it.

Epilogue

In this work, scientists have demonstrated their amazing creation - a composite hydrogel, the properties of which can be manipulated depending on the needs of the end user. The hydrogel they created is great for 3D printing via extrusion, something that previous hydrogels could not boast of. nine0003

Scientists say that water-based materials are not very strong, they are brittle and soft, which is quite expected. However, if alginate soft dendritic colloids and alginate gel bound by Ca 2+ ions are combined, a hydrogel with increased strength can be obtained. In other words, they have combined two different hydrogels into one with properties that are superior to those of its constituents.

Applications for the new hydrogel include medicine, the food industry, and soft robotics. But full use is still far away, since the hydrogel needs to be improved. In particular, the scientists want to modify the hydrogel so that it can be used in 3D printing of biomedical injection materials. nine0003

Thank you for your attention, stay curious and have a great week everyone. :)

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3D printed hydrogel cartilage, Chinese dynamic filling algorithms and 3D printed Australian satellites

News

In this issue, we will talk about experiences in the manufacture of durable hydragel implants on desktop 3D printers, Chinese developments in creating algorithms for dynamic filling of 3D models, and the launch of three Australian satellites with a 3D printed design at once. nine0003

Hydrogel Cartilage

Researchers at Duke University have created a high-strength composite hydrogel material to mimic cartilage. The material consists of 3D printed hydrogels with different mechanical properties - one provides the necessary rigidity, and the second provides elasticity. The compressive and tensile strength indicators exceed the characteristics of standard hydrogels by about two times, while the resulting composite does not deform upon contact with water. For the sake of the experiment, scientists printed a meniscus implant, that is, the cartilage lining of the knee joint. An important advantage of such endoprostheses will be the possibility of manufacturing on extremely cheap equipment: in the experiments, a budget desktop 3D printer costing only about $300, equipped with a syringe extruder, was used. nine0003

“We have greatly simplified the task of printing objects similar in mechanical properties to cartilage by offering a simple and inexpensive process. Available hydrogels do not reach the strength characteristics of human tissues and, as a rule, simply spread out at the outlet of the nozzle, because for the most part they consist of water. I hope this demonstration will help others interested in creating realistic and 3D printable hydrogels with mechanical properties that mimic human tissue even more closely,” said researcher Benjamin Wylie. The report of the research team is published at this link. nine0003

Chinese version of dynamic infill

Scientists at Southeast University in Nanjing, China, have published a study to develop algorithms that optimize the infill of 3D printed models. Emphasis is placed on the selective distribution of internal structures to maximize time and material savings while maintaining or even improving strength characteristics. The report of Chinese scientists is published at this link.

Recall that similar algorithms are already available to owners of MakerBot 3D printers using the Print proprietary slicer. The update was released a month ago, and the developers promised users up to 30% material savings on average when using the MinFill dynamic filling mode. Details here. nine0003

Australia returns to space

For the first time in fifteen years, Australian-made satellites will surf the near space: yesterday, the successful launch of an Atlas 5 launch vehicle carrying payloads for the International Space Station took place. This is even a kind of record, because before that only two Australian satellites had been in space, one of which was launched in 2002, and the first in the distant 1967. Now, three vehicles designed by scientists from the University of New South Wales went on board the ISS at once. nine0003

The launch of small satellites in the CubeSat format into free flight from the ISS will be carried out using a special installation of the NanoRacks company. Recall that additive technologies were used in the manufacture of the devices, and one of the tasks of the new Australian space program will be the testing of experimental 3D printed materials. More information about the creation and appointment of Australian satellites can be found at this link.

Do you have interesting news? Share your developments with us, and we will tell the whole world about them! We are waiting for your ideas at news@3Dtoday.


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