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.

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 two-way 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 impacted 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 bioelectronic 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.

Osteoporotic-related fractures are among the leading causes of chronic disease morbidity in Europe and in the US. While a significant percentage of fractures can be repaired naturally, in delayed-union and non-union fractures surgical intervention is necessary for proper bone regeneration. Given the current lack of optimized clinical techniques to adequately address this issue, bone tissue engineering (BTE) strategies focusing on the development of scaffolds for temporarily replacing damaged bone and supporting its regeneration process have been gaining interest. The piezoelectric properties of bone, which have an important role in tissue homeostasis and regeneration, have been frequently neglected in the design of BTE scaffolds. Therefore, in this study, we developed novel hydroxyapatite (HAp)-filled osteoinductive and piezoelectric poly(vinylidene fluoride-co-tetrafluoroethylene) (PVDF-TrFE) nanofibers via electrospinning capable of replicating the tissue’s fibrous extracellular matrix (ECM) composition and native piezoelectric properties. The developed PVDF-TrFE/HAp nanofibers had biomimetic collagen fibril-like diameters, as well as enhanced piezoelectric and surface properties, which translated into a better capacity to assist the mineralization process and cell proliferation. The biological cues provided by the HAp nanoparticles enhanced the osteogenic differentiation of seeded human mesenchymal stem/stromal cells (MSCs) as observed by the increased ALP activity, cell-secreted calcium deposition and osteogenic gene expression levels observed for the HAp-containing fibers. Overall, our findings describe the potential of combining PVDF-TrFE and HAp for developing electroactive and osteoinductive nanofibers capable of supporting bone tissue regeneration.