In organ donation and transplantation, the high demand for organs exceeds supply, greatly, leading to limited access to transplantation. The waiting lists for a heart transplant in the UK increased by c. 134%, from 2010 to 2019, combined with a disproportionate number of available organs. In the US, in 2014, around 17,107 kidney transplants took place, in disparity with a waiting list that increased to peak at about 121,678 individuals in 2016. This imbalance in organ availability versus need is observed worldwide, and this trend is aggravated by common drawbacks and challenges associated with organ rejection, complications related to the use of immune-suppressing medication, and the limited lifespan of transplanted organs. In 2023, the global figures were appalling, besides the World Health Organization (WHO) 13th General Programme of Work (2019-2023), which was planned to strengthen international cooperation, to leverage key resources and to enhance international policies, to better the statistics.

Transplantation of human cells, tissues and organs is a life-saving mechanism when alternative solutions are not an option. Haematopoietic stem cell grafts are used to treat leukaemia patients, corneal grafts can cure corneal blindness, and severe heart failure can be remediated via coronary transplantation. Xenotransplantation studies are becoming popular, with a large body of the literature reporting on novel techniques to overcome animal-to-human compatibility drawbacks, to leverage the shortfall in human material for transplantation. From this perspective, tissue engineering, regenerative cell-tissue technology, synthetic materials, and AI-micro-nano automation programmed into bio-compatible chipsets, ultimately lead to genetically designed organs and (or) biocompatible artificial organs that are groundbreaking alternatives for the burden of cell, tissue, and organ donation and transplantation.

It has commonly been assumed that synergistic approaches are promising in cell and tissue regeneration and engineering, and in the design of bio-compatible artificial organs, where limitations are leveraged and strengths are enhanced by combined approaches. The contemporary cell, tissue, and whole organ engineering combines gene-redesign and regenerative approaches as the ones based on stem cell technology. However, artificial organs may go one step ahead, benefiting from nano-materials combined with programmable chipsets. Nanocomposites are promising as drug delivery systems, encapsulating myriad of clinically relevant compounds -- e.g., plant metabolites; reducing non-targeted interactions with the immune system and optimising drug distribution.

Pioneering research is creating biocompatible nanoparticles that can be programmed to deliver regenerative composites and plant-derived compounds in a defined timescale and to monitor their concentration, at target locations, within the human body. Nanotechnology has been also widely applied in both prognosis and diagnosis, allowing the implementation of minimally invasive clinical approaches in precision medicine (e.g., magnetic fields driving superparamagnetic metal nanoparticles within the human body). It is fundamental for these applications to optimally exploit the physical properties of the materials used to manufacture these biocompatible complexes. Indeed, while artificial organs may normally be static structures, their coupling with dynamically moving imaging probes, circulating tissue regeneration stem particles, and other biocompatible dynamic elements are of great interest for the scientific community. Therefore, this Research Topic highlights the important role of novel materials that allow the creation of autonomously driven micro- and nano-robots and that modulate the external-field-based directed motion of micro- and nano automatons used in clinical diagnosis, treatment, and prognosis. Nano sensors such as the graphene nano-complexes (graphene transistors and electrodes) have boosted bioelectronics, conceiving adaptive implant-tissue interfaces, and reducing the risk of immune toxicity-driven side effects. This Research Topic highlights Artificial Intelligence (AI) models that have shown great potential supporting biomedicine, and enhancing medical robotics and automation, being implemented in nano-micro bio-compatible chipsets, to forecast, classify, mimic, and orchestrate the activity of autonomous devices. This Research Topic highlights stem cell technology, genetic engineering, and plant metabolites commonly applied in regenerative medicine.

In conclusion, this collection of manuscripts introduces state of the art groundbreaking technology in cell and tissue engineering, in tissue regeneration, and in the design of biocompatible artificial organs. This collection of manuscripts covers reviews and technical essays, along with state of the art methods and protocols.

The collection is organised in four subtopics:

(1) Gene-Driven Synthetic Biology Strategies and Nano-Biotechnology in Next Generation Artificial Organs
and Cell-Tissue Engineering
(2) AI-Based Forecasting, Medical Robotics and Automation
(3) Nano-Automatons in Minimally Invasive Medical Diagnosis, Treatment, and Prognosis, and
(4) Clinical Nanotechnology boosted by Plant Metabolites in Regenerative Medicine.

The first subtopic presents technical reviews, methods and protocols about artificial organs and cell-tissue engineering, benefiting from state of the art technologies.
The second subtopic focuses on AI forecasting and automation, ideally used in medical robotics and programmable chipsets, applicable to implantable medical devices.
The third subtopic shows the technical aspects of micro and nano automatons.
The fourth subtopic is centered in tissue regeneration, ideally supported by nanocomposites, combined with plant-derived compounds.

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Frontiers in Medical Technology

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