Tissue Engineering (TE) strategies combining stem cells, biomaterial scaffolds, and biochemical/physical cues have emerged as promising approaches for the repair/replacement of injured tissues and organs. However, a direct translation of TE strategies to clinical use remains challenging due to scientific, technical, and regulatory limitations. TE approaches are mostly adopted for the fabrication of advanced and reliable biomimetic models for basic and pre-clinical studies, disease research, drug and toxicological screening, and safety assessment of biomedical products. Biomimetic models are also gaining attention in space biology for studying the effects of microgravity and radiation on human physiology.

Despite the great recent scientific advances in the field, very few approaches achieved successful clinical translation. In this scenario, bioprocessing methods, e.g. bioreactor technologies, are crucial for the scalable manufacturing of functional cell-based tissue-engineered constructs. Moreover, recently, tissue-specific bioreactor systems have been successfully developed and used to create controlled in vivo-like microenvironments to support cell differentiation/tissue maturation and to study the physiopathology of diseases like cancer as well as their response to therapies. Furthermore, the use of advanced biomaterial processing techniques, e.g., 3D-bioprinting or microfabrication, to fabricate tissue constructs with higher architectural complexity and biomimicry is emerging as a very promising approach. In parallel, the development and use of increasingly sophisticated in silico models based on advanced computer modelling and artificial intelligence (AI) are becoming crucial to optimize, control, and automate TE strategies. Advanced in vitro and in silico approaches have been recently recognized by regulatory bodies, such as the FDA, as effective alternatives to animal tests and overall they are becoming indispensable for a broader and successful translation of TE into clinical practice.

Advances in bioprocessing technologies have allowed the scalable and reproducible fabrication of TE constructs with higher structural complexity and functionality, achieving a closer mimicry of native-like tissue microenvironments. This Research Topic aims to provide an overview of the major advances in bioprocessing technologies and methods for TE and regenerative medicine applications. Relevant strategies involving bioreactors, microfluidic systems, 3D bio-printed tissues and organ-on-chips that provide biomimetic, monitored, and controlled 3D in vitro culture conditions for the biophysical stimulation of cells or TE constructs towards improved functionality will receive special attention. Novel stem cell bioengineering and biomaterial-based approaches applied to regenerative medicine and in vitro disease modelling are also of special interest, together with new technologies for biological tissue characterization or for identifying and testing innovative pharmacological treatments. Moreover, innovative in silico and AI-based approaches paving the way towards optimized and automated TE strategies are also welcomed.

This Research Topic invites contributions (Original Research articles and Literature Review manuscripts) describing and discussing the most recent and innovative developments in bioprocessing TE strategies for regenerative medicine and disease modelling applications, leveraged by advances in bioreactor systems, novel biomaterials, 3D bioprinting methods, imaging and biosensing, computational modelling, AI and machine learning, among others.

Specific topics and themes of this Research Topic will include but are not limited to:

- In vitro 3D models;

- Novel bioprocesses for the expansion of human stem cells and their derived products (e.g., extracellular vesicles);

- In vitro 3D bio-printed tissue and organs models;

- Biomimetic bioreactors, microfluidics, and organ-on-chips;

- Sensors and monitoring devices for in vitro 3D cultures;

- Test bench technologies;

- In silico and artificial intelligence approaches;

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Frontiers in Bioengineering and Biotechnology

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