iBB

Advances in bioprocessing technologies have allowed the scalable and reproducible fabrication of tissue engineering (TE) constructs with higher structural complexity and functionality, achieving a closer mimicry of native-like microenvironments. The Research Topic co-edited by iBB researchers Dr. João C. Silva and Dr. Carlos Rodrigues in collaboration with Prof. Eirini Velliou (University College London, UK) and Prof. Diana Massai (Politecnico di Torino, Italy) 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.

Endogenous human brain tissue is not easily available for studying neurodevelopment and neurodegenerative diseases. However, human pluripotent stem cells (PSCs) have been used to generate a variety of glial and neuronal cells of the central nervous system. Still, reproducible protocols for generating in vitro models of the human cerebellum are scarce. In this context, Silva et al. describe the scalable production of human PSC-derived cerebellar organoids using single-use vertical-wheel bioreactors. The transcriptomic profile of cerebellar organoids derived under dynamic conditions demonstrates a faster cerebellar differentiation combined with significant enrichment of extracellular matrix and upregulation of transcripts involved in angiogenesis when compared with the static protocol. The authors anticipate that large-scale production of cerebellar organoids may help developing models for drug screening, toxicological tests and studying pathological pathways involved in cerebellar degeneration.

In a new paper published in Frontiers in Bioengineering and Biotechnology, SCERG-iBB researchers in collaboration with colleagues from the Institute of Molecular Medicine (iMM) describe a novel differentiation strategy that uses defined medium to generate Purkinje cells, granule cells, interneurons, and deep cerebellar nuclei projection neurons, that self-formed and matured into electrically active cells. This research is expected to result in better models for the study of cerebellar dysfunctions and represent an important advancement towards the development of autologous replacement strategies for treating cerebellar degenerative diseases.

The project "CardioWheel: Upscaling the Production of Human Pluripotent Stem Cell-derived Cardiomyocytes using Vertical-Wheel Bioreactors" has been recommended for funding by FCT (2017 Call for SR&TD Project Grants). The goal of CardioWheel is the application of bioreactor technology for human Pluripotent Stem Cell expansion and cardiomyocyte differentiation in a single process, culturing cells in suspension in the novel single-use Vertical-Wheel Bioreactors. These bioreactors will be characterized using computational fluid dynamics and this knowledge will be used to scale up the culture. The generated cells will be tested for functional and pharmacological activity to demonstrate their applicability in drug discovery and regenerative medicine. The project, which falls within the scientific area of Chemical Engineering, is headed by Carlos Rodrigues and Joaquim Cabral from SCERG-iBB.

CellAgri Portugal, the Portuguese Association for Cellular Agriculture Development, is a recently created independent non-profit organization, headquartered at IST-TagusPark.

The mission of CellAgri Portugal is to facilitate and encourage the cooperative development of cellular_agriculture in Portugal as well as to inform the public about the industrial, scientific, and technological developments in the field involving the Portuguese community worldwide.

Joaquim Cabral is the president of CellAgri Portugal and Carlos Rodrigues is the executive director. CellAgri Portugal also counts with the iBB researchers Frederico Ferreira, Ana Fernandes-Platzgummer, Paola Alberte, and the iBB PhD students Diana Marques and Hélder Tavares.

The project "SMART:New technologies and strategies for Stem cell Manufacturing bioprocess monitoring and ARTificial intelligence-based modeling" has been recommended for funding by FCT (2020 Call for SR&TD Project Grants). The goal of SMART is to develop new monitoring and modeling strategies envisaging more efficient bioreactor-based processes for the manufacturing of human induced Pluripotent Stem Cell-derived cardiomyocytes for biomedical applications, using artificial intelligence to integrate bioprocess monitoring data with biological data. The project, which falls within the scientific area of Chemical Engineering, is headed by Carlos Rodrigues from SCERG-iBB.

During crude oil extraction, the reduction in temperature and pressure results in the precipitation of paraffin wax, which may accumulate inside production tubes, pipelines, and also in tankers during petroleum transportation. Few bacterial strains are able to degrade this type of solid substrates. In a paper, published  in Biotechnology Journal, Carlos Rodrigues and Carla CCR de Carvalho (BERG-iBB) evaluate the biodegradation of paraffin by Rhodococcus erythropolis cells. The cells could grow as a thick biofilm over the solid substrate and rapidly degrade paraffin when it was supplied in the form of microparticles. The phenotypic adaptations allowing the cells to degrade the 20-40 chain hydrocarbons are discussed in the paper.