Bioprinting has been a promising additive manufacturing technology that has proven its competency for biomaterials, cells, tissues, and human organs. Through manipulation of pre-, post-printing processes, bioprinting has been able to find wide applications in drug development, fabrication of organs, tissue engineering, wound management, treatment, etc. However, these are the fields that traditionally fit into the application area of bioprinting.

Evolving needs and customer-centric solutions have put a demand on creating new biomedical devices. This has also highlighted the need for new manufacturing ways that are compatible with new forms factors, designs, and materials. So far bioprinting has caused the excitement for organ printing, but we have somehow overlooked its potential for other fields. The use of bioprinting methods may extend far and wide beyond what it is currently used for. 

Bioelectronics is an area that encompasses electronic devices that find application in the healthcare and biomedical sector. This is an exciting field, which lies at the interdisciplinary boundaries of electronic engineering, biology, and manufacturing. Research at the intersection of such fields has the potential to become a pillar of medical treatment and play a key role in the future of MedTech innovation. Bioelectronic devices are manufactured using traditional electronic technologies. Although these technologies are reliable and have been standardized, they use high-temperature and vacuum processing that is not compatible with new emerging materials.

Our research group at Aarhus University, Denmark has been working extensively in the area of bioelectronics trying to combine biology with electronics in new ways through the bioprinting route. We are looking to go beyond the traditional roles of bioprinting, i.e. to replace damaged tissues and organs. We believe that bioprinting is a powerful tool that can contribute to building the next generation of bioelectronic devices. By pushing the boundaries of the biomedical field. We have created new-age devices for wound management, muscle atrophy, and health monitoring well-suited for fabricating skin-compatible and soft devices.  

Quest for new biodegradable and biocompatible materials

Electronics have made a tremendous impact on human society, and this has also led to issues of electronic waste pilling on earth, just like plastic. This has led to research efforts in the direction of creating new electronic materials that are biodegradable. When it comes to biomedical devices, there is an additional need for the devices to be biocompatible and have transient nature. There are various scenarios in healthcare where electronics need to operate for a limited time and then degrade generating biologically safe products. Our research group is focused on creating a library of novel materials that are environmentally safe and have good electronic properties. We have started work on piezoresistive, piezoelectric, and conducting materials that are prepared using green chemistries, and possess different water dissolution rates. The as-synthesized materials are then converted into printable inks to create devices with a specific thickness. The focus is more on polymer materials due to their biodegradability and ease of processing. We have developed a printable piezoelectric material based on polyvinylidene difluoride (PVDF) that shows remarkable properties to make sensitive sensors. The material can be partially degraded but uses non-toxic reagents. The natural extension of this project was to work on a fully biodegradable piezoelectric material. This poly-L-lactic acid (PLLA) based material can have tunable properties of amorphous nature and crystallinity, thus giving it a unique spin for various applications. In another project, we have taken inspiration from mussels and created polyvinyl alcohol (PVA) and dopamine composite to have not just biodegradable properties but good adhesive qualities as well.

Next-generation bioelectronics

Working with new materials requires new fabrication methods to make devices. We are exploring several different bioprinting methods namely 2D, 3D, inkjet-, laser- and extrusion- to print next-generation bioelectronics devices. Leveraging the attractive features of bioprinting with traditional techniques allows us to create new-form factors with complete integration for soft devices.  

Figure 3 shows some of the printed devices fabricated at PET lab. pH patch sensor used bioprinting to print a multilayered architecture to monitor the pH levels in the wound extrude and also the hydration around the wound site. A flexible pressure sensor was created on eco flex via inkjet printing. The printed ink and the substrate can also be stretched without losing functionality. The electrostimulation patch was an interesting study, wherein room-temperature metal ink was printed and sandwiched between printed hydrogel layers. The fully printed patch did not require any post-processing or sintering to functionalize the materials. The patch was stable in bio-medium for several dates and no ink leakage was observed. The patch was tested for biocompatibility using C2C12 and fibroblast cells. All these patches are partially biodegradable. To move towards bioresorbable electronics, which degrades completely inside the human body environment, we printed an antenna circuit on a melt-drawn Polycaprolactone (PLC) biodegradable polymer coated with a hydrogel. Our current research, thus, is directed towards creating conformal, flexible, and biocompatible devices for future medical applications through the printing route.

Research Goals

Forward progress will require contributions from a multidisciplinary team. Our research group is composed of electronics engineering, material scientists, chemistry, and biomedical experts. What is also unique about our group is that we research fundamental science pertaining to materials but also have projects higher on technology readiness level (TRL) with industry partners. Through understanding the science behind bioprinting, we are hopeful to create impactful work for the healthcare and biomedical sector. 

About the Author:

Shweta Agarwala is a tenure-track assistant professor at Electrical and Computer Engineering, Aarhus University. Her vision is to enable component and wire-free electronic circuits that are flexible, bendable, conformable, and biodegradable. She is achieving this through material innovation and the 3D printing routes by printing electronics on unconventional substrates for next-generation electronics especially catering to the healthcare and biomedical sector. Shweta is the author of more than 40 peer-reviewed papers published in internationally renowned journals, books, and conferences. She is the vice-chair for the Women in Engineering chapter in IEEE Denmark section and an enthusiast STEM advocate. 

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The post Rethinking Bioprinting for Sustainable Bioelectronics appeared first on 3DHeals.

(Featured Image: Planar lattice structure and b)

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Exciting things are happening in the fields of tissue engineering and regenerative medicine, all thanks to 3D bioprinting. The high precision and convenient operation allow 3D bioprinting to expand into new areas. Current research efforts all over the world are now leading to innovations in regenerative medicine, vascularized printed organs and replicating organ functionalization. However, to attain reproducibility or to print clinically relevant forms and sizes, material control is important. The implementation of bioprinting relies on the geometrical accuracy of replicating the design file. This, in turn, depends on printing parameters and material properties. Studying and understanding the correlation between hydrogel material characteristics and successful bioprinting is important to obtain functional 3d constructs to fulfill intended applications. Much research has been done on ink properties and printing optimization. However, little attention has been paid to the relation between hydrogel parameters and printing fidelity. Most of the users are uninformed about the properties of hydrogels that should be kept in mind for obtaining a good 3D printed construct for the intended application. There are many material parameters that influence the printing process and resolution directly and can be tuned to achieve a finely tuned process.

Be mindful of Gelation Time

Not all hydrogels are created equal. Gelation time in hydrogel varies according to their crosslinking chemistry. This parameter has to be kept in mind when choosing a hydrogel for a particular application. Collagen has been found to be the slowest to gel so far [1]. 

How is the swelling?

Swelling is defined as the ratio of the mass of swollen hydrogel to the mass at the equilibrium. Swelling contractile characteristics can be of central concern for producing biological constructs especially for skin and wound applications. The swelling rate also governs the stability, as one would want the bioprinted hydrogel to be in place for a sufficient amount of time.

Against the gravity

Care has to be taken to avoid diffusion of hydrogels in one another when overlapping layers are printed. The diffusion phenomenon will make the printed pores to decrease in diameter when printing more layers. For a lattice structure, with an increase in line distance, the diffusion rate can be slowed down thus reducing the diffusion effect (fig 1).

Figure 1: Graph depicting the relationship between line distance and diffusion rate in a lattice structure (reprinted with permission from ref. 2)]. 

Control your curves

Fabricating sharp angles through 3D bioprinting is a challenge. Sharp bends create material overlap resulting in non-uniform thickness, which eventually leads to printing failures. Most of the time the construct has to be re-designed to avoid such issues. An alternate way is to reduce the extrusion rate for such prints.

The Game of Viscosity

This material property is the most important and well-understood for printing. For hydrogels, the viscosity (η) should ideally lie between 300-30000 cps (centipoise) for most printers. Although attempts have been made to print hydrogels with η˃30000 cps using higher pressure systems, however, the printing is not reproducible and stable with time. 

References:

[1]. S. V. Murphy, A. Skardal, A. Atala, Evaluation of hydrogels for bio-printing applications, Journal of Biomedical Materials Research 101A (2013) 272-284.

[2]. Y. He, F. F. Yang, H. M. Zhao, Q. Gao, B. Xia, J. Z. Fu, Research on the printability of hydrogels in 3D bioprinting, Scientific Reports 6 (2016) 29977.

About the Author:

Shweta Agarwala is Assistant professor at Department of Engineering, Aarhus University (Denmark). Dr. Agarwala graduated in electronics engineering from Nanyang Technological University, Singapore and obtained her Ph.D. in the same field from the National University of Singapore. Her research is directed towards printed electronics for flexible devices and bioelectronics. She is pioneering new routes to put electronics on unconventional surfaces to enable future generation healthcare. 

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The post Control your 3D Bioprinting Hydrogels appeared first on 3DHeals.

Want to write a piece for 3DHEALS Expert Corner? Email us: info@3dheals.com

“Bioprinting” is a well-known word now, thanks to burgeoning research papers and blogs on the theme. 3D bioprinting has been at the center point of activity and news hub, all thanks to the demonstrated potential. As more and more researchers join the bioprinting community, the promise that it brings to the table seems more realistic. When I started my research in this field five years back, I was amazed at the possibilities that bioprinting could bring to healthcare, biomedical and regenerative medicine. However, being trained as an electronics engineer, I saw something beyond the obvious. Could bioprinting help in combining two distinct fields of biology and electronics to create new avenues for healthcare? 

Bioelectronics is the area, which deals with interfacing electrical devices and circuits with biological materials and species. Pacemakers, artificial prosthetics, and implantable devices belong to this class that has been around for some time. However, most of the present day bioelectronics devices use rigid electronic components, which are a mismatch for soft human tissues. This incompatibility causes issues in the long run, for example, tissues scarring and infections. The vision has been to replace the rigid electronics with flexible and if possible soft electronics. Being an electronic engineer, I saw a huge potential where bioprinting can be put to use to achieve this target. 

I have been making small research efforts in this domain, where bioprinting is used to put down conformal electronics on biomaterials loaded with cells. The drop-on-demand bioprinting technique of microvalve is well-suited for printing low viscosity electronic conducting inks and hydrogels. This paves the way to fabricate external bioelectronic and even implantable devices that have Young’s modulus close to human tissues. The central idea is to encapsulate electronic between biomaterials that will support cell growth. Embedding electronics with biomaterials requires added functionality of biocompatibility, stability in wet environment and flexibility. Our paper “A novel 3D bioprinted flexible and biocompatible hydrogel bioelectronic platform” highlighted that bioprinting can achieve a 3D platform by printing successive layers of biomaterials and electronics. Bioprinting gives the freedom to use different nozzle sizes and control the pressure depending on the viscosity of the inks. This makes it possible to print low viscosity nanoparticle inks for electrical circuits in between layers of high viscosity biomaterials. 

Thus bioprinting functions as a novel tool for design innovation. One can, hence, see the potential of this technology other than in tissue engineering and organ fabrication. Bioprinting can well be a tool to make a new type of healthcare devices. A field that once was though a thing of future is quickly becoming reality, thanks to bioprinting. 

About the author

Shweta Agarwala is Assistant professor at Department of Engineering, Aarhus University (Denmark). Dr. Agarwala graduated in electronics engineering from Nanyang Technological University, Singapore and obtained her Ph.D. in the same field from the National University of Singapore. Her research is directed towards printed electronics for flexible devices and bioelectronics. She is pioneering new routes to put electronics on unconventional surfaces to enable future generation healthcare. 

Related Articles:

3D Printing for the Human Organ Shortage: Putting Bio back into Bioprinting

3D Bioprinting: Chiasm of Art, Design, Science, Technology, and Evolution

3D Printing (and Bioprinting) will help healthcare with a quantum leap?

3D Bioprinting: Truth is Beautiful

The post Enabling Futuristic Bioelectronics With Bioprinting: Beyond the Obvious appeared first on 3DHeals.