Additive manufacturing of electrochemical systems and their application in bioelectronic medicine

Bioelectronic medicine is a growing field where a combination of electronic and biological systems are used to induce a therapeutic response. Despite the advancements achieved in the area with the production of retinal and cochlear implants, vagus nerve stimulators and wearable biosensors, there are some challenging limitations, including a poor integration in the bioelectronic interfaces and low specificity of the outputs. In order to solve this, additive manufacturing and electrochemical approaches are explored in this work. Bioelectronic interfaces were produced in situ, growing silver microwires between CHO cells, offering an example of engineering of seamless functional interfaces controlled remotely. A model of wireless intracellular bioelectronic communication was also provided, where gold nanoparticles (AuNPs) conjugated with a redox-dependent fluorescent porphyrin were used as intracellular transducers, reducing the typical invasiveness of electronic systems and converting electronic inputs into a fluorescent output when an external electric field was applied. The last part of the investigation was to create conductive polymeric scaffolds fabricated by two-photon polymerisation (2PP) with nano- and micro-topographies to provide mechanical and electrical cues to human induced pluripotent stem cells-derived cardiomyocytes and advance their in vitro maturation state

Electrochemically stimulating developments in bioelectronic medicine

Cellular homeostasis is in part controlled by biological generated electrical activity. By interfacing biology with electronic devices this electrical activity can be modulated to actuate cellular behaviour. There are current limitations in merging electronics with biology sufficiently well to target and sense specific electrically active components of cells. By addressing this limitation, researchers give rise to new capabilities for facilitating the twoway transduction signalling mechanisms between the electronic and cellular components. This is required to allow significant advancement of bioelectronic technology which offers new ways of treating and diagnosing diseases. Most of the progress that has been achieved to date in developing bioelectronic therapeutics stimulate neural communication, which ultimately orchestrates organ function back to a healthy state. Some devices used in therapeutics include cochlear and retinal implants and vagus nerve stimulators. However, all cells can be effected by electrical inputs which gives rise to the opportunity to broaden the use of bioelectronic medicine for treating disease. Electronic actuation of non-excitable cells has been shown to lead to ‘programmed’ cell behaviour via application of electronic input which alter key biological processes. A neglected form of cellular electrical communication which has not yet been considered when developing bioelectronics therapeutics is faradaic currents. These are generated during redox reactions. A precedent of electrochemical technology being used to modulate these reactions thereby controlling cell behaviour has already been set. In this mini review we highlight the current state of the art of electronic routes to modulating cell behaviour and identify new ways in which electrochemistry could be used to contribute to the new field of bioelectronic medicine

multifunctional bioinstructive 3d architectures to modulate cellular behavior

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Printing bio-hybrid materials for bioelectronic cardio-3D-cellular constructs

Conductive hydrogels are emerging as promising materials for bioelectronic applications as they minimise the mismatch between biological and electronic systems. We propose a strategy to bioprint bio-hybrid conductive bioinks based on decellularized extracellular matrix (dECM) and multi-walled carbon nanotubes. These inks contained conductive features and morphology of the dECM fibres. Electrical stimulation (ES) was applied to bioprinted structures containing human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). It was observed that in the absence of external ES, the conductive properties of the materials can improve the contractile behaviour of the hPSC-CMs and this effect is enhanced under the application of external ES. Genetic markers indicated a trend towards a more mature state of the cells with upregulated calcium handling proteins and downregulation of calcium channels involved in the generation of pacemaking currents. These results demonstrate the potential of our strategy to manufacture conductive hydrogels in complex geometries for actuating purposes

Additive manufacturing of electrochemical systems and their application in bioelectronic medicine

Bioelectronic medicine is a growing field where a combination of electronic and biological systems are used to induce a therapeutic response. Despite the advancements achieved in the area with the production of retinal and cochlear implants, vagus nerve stimulators and wearable biosensors, there are some challenging limitations, including a poor integration in the bioelectronic interfaces and low specificity of the outputs. In order to solve this, additive manufacturing and electrochemical approaches are explored in this work. Bioelectronic interfaces were produced in situ, growing silver microwires between CHO cells, offering an example of engineering of seamless functional interfaces controlled remotely. A model of wireless intracellular bioelectronic communication was also provided, where gold nanoparticles (AuNPs) conjugated with a redox-dependent fluorescent porphyrin were used as intracellular transducers, reducing the typical invasiveness of electronic systems and converting electronic inputs into a fluorescent output when an external electric field was applied. The last part of the investigation was to create conductive polymeric scaffolds fabricated by two-photon polymerisation (2PP) with nano- and micro-topographies to provide mechanical and electrical cues to human induced pluripotent stem cells-derived cardiomyocytes and advance their in vitro maturation state

A Concise Review on Electrospun Scaffolds for Kidney Tissue Engineering

Chronic kidney disease is one of the deadliest diseases globally and treatment methods are still insufficient, relying mostly on transplantation and dialysis. Engineering of kidney tissues in vitro from induced pluripotent stem cells (iPSCs) could provide a solution to this medical need by restoring the function of damaged kidneys. However, implementation of such approaches is still challenging to achieve due to the complexity of mature kidneys in vivo. Several strategies have been defined to obtain kidney progenitor endothelial and epithelial cells that could form nephrons and proximal tube cells, but these lack tissue maturity and vascularisation to be further implemented. Electrospinning is a technique that has shown promise in the development of physiological microenvironments of several tissues and could be applied in the engineering of kidney tissues. Synthetic polymers such as polycaprolactone, polylactic acid, and poly(vinyl alcohol) have been explored in the manufacturing of fibres that align and promote the proliferation and cell-to-cell interactions of kidney cells. Natural polymers including silk fibroin and decellularised extracellular matrix have also been explored alone and in combination with synthetic polymers promoting the differentiation of podocytes and tubular-specific cells. Despite these attempts, further work is still required to advance the applications of electrospun fibres in kidney tissue engineering and explore this technique in combination with other manufacturing methods such as bioprinting to develop more organised, mature and reproducible kidney organoids

3D Bioprinting of Novel κ-Carrageenan Bioinks: An Algae-Derived Polysaccharide

Novel green materials not sourced from animals and with low environmental impact are becoming increasingly appealing for biomedical and cellular agriculture applications. Marine biomaterials are a rich source of structurally diverse compounds with various biological activities. Kappa-carrageenan (κ-c) is a potential candidate for tissue engineering applications due to its gelation properties, mechanical strength, and similar structural composition of glycosaminoglycans (GAGs), possessing several advantages when compared to other algae-based materials typically used in bioprinting such as alginate. For those reasons, this material was selected as the main polysaccharide component of the bioinks developed herein. In this work, pristine κ-carrageenan bioinks were successfully formulated for the first time and used to fabricate 3D scaffolds by bioprinting. Ink formulation and printing parameters were optimized, allowing for the manufacturing of complex 3D structures. Mechanical compression tests and dry weight determination revealed young’s modulus between 24.26 and 99.90 kPa and water contents above 97%. Biocompatibility assays, using a mouse fibroblast cell line, showed high cell viability and attachment. The bioprinted cells were spread throughout the scaffolds with cells exhibiting a typical fibroblast-like morphology similar to controls. The 3D bio-/printed structures remained stable under cell culture conditions for up to 11 days, preserving high cell viability values. Overall, we established a strategy to manufacture 3D bio-/printed scaffolds through the formulation of novel bioinks with potential applications in tissue engineering and cellular agriculture