Microbial-derived materials are emerging for applications in biomedicine, sensors, food, cosmetics, construction, and fashion. They offer considerable structural properties and process reproducibility compared to other bio-based materials. However, challenges related to efficient and sustainable large-scale production of microbial-derived materials must be addressed to exploit their potential fully. This review analyzes the synergistic contribution of circular, sustainable, and biotechnological approaches to enhance bacterial cellulose (BC) production and fine-tune its physico-chemical properties. BC was chosen as an ideal example due to its mechanical strength and chemical stability, making it promising for industrial applications. The review discusses upcycling strategies that utilize waste for microbial fermentation, simultaneously boosting BC production. Additionally, biotechnology techniques are identified as key to enhance BC yield and tailor its physico-chemical properties. Among the different areas where cellulose-based materials are employed, BC shows promise for mitigating the environmental impact of the garment industry. The review emphasizes that integrating circular and biotechnological approaches could significantly improve large-scale production and enhance the tunability of BC properties. Additionally, these approaches may simultaneously provide environmental benefits, depending on their future progresses. Future advancements should prioritize circular fermentation and biotechnological techniques to expand the potential of BC for sustainable industrial applications.

Over the past decade, the development of three-dimensional (3D) models has increased exponentially, facilitating the unravelling of fundamental and essential cellular mechanisms by which cells communicate with each other, assemble into tissues and organs and respond to biochemical and biophysical stimuli under both physiological and pathological conditions. This section presents a concise overview of the most recent updates on the significant contribution of different types of 3D cell cultures including spheroids, organoids and organ-on-chip and bio-printed tissues in advancing our understanding of cellular and molecular mechanisms. The case studies presented include the 3D cultures of breast cancer (BC), endometriosis, the liver microenvironment and infections. In BC, the establishment of 3D culture models has permitted the visualization of the role of cancer-associated fibroblasts in the delivery of exosomes, as well as the significance of the physical properties of the extracellular matrix in promoting cell proliferation and invasion. This approach has also become a valuable tool in gaining insight into general and specific mechanisms of drug resistance. Given the considerable heterogeneity of endometriosis, 3D models offer a more accurate representation of the in vivo microenvironment, thereby facilitating the identification and translation of novel targeted therapeutic strategies. The advantages provided by 3D models of the hepatic environment, in conjunction with the high throughput characterizing various platforms, have enabled the elucidation of complex molecular mechanisms underlying various threatening hepatic diseases. A limited number of 3D models for gut and skin infections have been developed. However, a more profound comprehension of the spatial and temporal interactions between microbes, the host and their environment may facilitate the advancement of in vitro, ex vivo and in vivo disease models. Additionally, it may pave the way for the development of novel therapeutic approaches in diverse research fields. The interested reader will also find concluding remarks on the challenges and prospects of using 3D cell cultures for discovering cellular and molecular mechanisms in the research areas covered in this review.

The main problems in drug development are connected to enormous costs related to the paltry success rate. The current situation empowered the development of high‐throughput and reliable instruments, in addition to the current golden standards, able to predict the failures in the early preclinical phase. Being hepatotoxicity responsible for the failure of 30% of clinical trials, and the 21% of withdrawal of marketed drugs, the development of complex in vitro models (CIVMs) of liver is currently one of the hottest topics in the field. Among the different fabrication techniques, 3D‐bioprinting is emerging as a powerful ally for their production, allowing the manufacture of three‐dimensional constructs characterized by computer‐controlled and customized geometry, and inter‐batches reproducibility. Thanks to these, it is possible to rapidly produce tailored cell‐laden constructs, to be cultured within static and dynamic systems, thus reaching a further degree of personalization when designing in vitro models. This review highlights and prioritizes the most recent advances related to the development of CIVMs of the hepatic environment to be specifically applied to pharmaceutical research, with a special focus on 3D‐bioprinting, since the liver is primarily involved in the metabolism of drugs.

Detection and monitoring of lactate and glucose levels in biological fluids and cell cultures are essential for understanding metabolic disorders. While electrochemical biosensors are commonly used, traditional enzymatic sensors face challenges related to stability, reproducibility, and cost. To address these limitations, we developed non-enzymatic sensors for lactate and glucose detection using nanostructured nickel oxide (NiO)-modified screen-printed carbon electrodes. The sensors were fabricated by drop-casting a NiO/Nafion/ethanol dispersion onto the working electrode, and their performance was evaluated using cyclic voltammetry and amperometry. Optimal sensitivity and linearity were achieved at a working potential of ∼0.5 V. The sensors exhibited linear responses for both lactate and glucose in the 0.1-5 mM range, with detection limits of 0.03 mM (lactate) and 0.025 mM (glucose), and sensitivities of 1.564 μA/mM (lactate) and 1.842 μA/mM (glucose) in 0.1 M NaOH-KCl electrolyte. To address glucose interference in lactate sensing, dual-sensing strategies were employed by varying Nafion concentration, applying differential potentials, or modifying the sensors with Prussian Blue to achieve selective detection. Validation against commercial lactate and glucose assay kits in cell culture medium showed good agreement, confirming the sensors' accuracy. Finally, the sensor was integrated with a microfluidic chip, demonstrating its potential as a flow-through, enzyme-free metabolic sensor for future organ-on-a-chip applications.

Bioprinting is a key technique to fabricate cell-laden volumetric constructs with controlled geometry. It can be used not only to replicate the architecture of a target organ but also to produce shapes that allow for the mimicry, in vitro, of specific desired features. Among the various materials suitable to be processed with this technique, sodium alginate is currently considered one of the most appealing because of its versatility. To date, the most widespread strategies to print alginate-based bioinks exploit external gelation as a primary process, by directly extruding the hydrogel-precursor solution into a crosslinking bath or within a sacrificial crosslinking hydrogel, where the gelation takes place. In this work, we describe the print optimization and the processing of Hep3Gel: an internally crosslinked alginate and ECM-based bioink for the production of volumetric hepatic tissue models. We adopted an unconventional strategy, by moving from the reproduction of the geometry and the architecture of liver tissue to the use of bioprinting to fabricate structures that can promote a high degree of oxygenation, as is the case with hepatic tissue. To this end, the design of structures was optimized by employing computational methods. The printability of the bioink was then studied and optimized through a combination of different a priori and a posteriori analyses. We produced 14-layered constructs, thus highlighting the possibility to exploit internal gelation alone to directly print self-standing structures with finely controlled viscoelastic properties. Constructs loaded with HepG2 cells were successfully printed and cultured in static conditions for up to 12 d, underlining the suitability of Hep3Gel to support mid/long-term cultures.

The intrinsic heterogeneity of bacterial niches should be retained in in vitro cultures to represent the complex microbial ecology. As a case study, mucin‐containing hydrogels ‐CF‐Mu³Gel ‐ are generated by diffusion‐induced gelation, bioinspired on cystic fibrosis (CF) mucus, and a microbial niche challenging current therapeutic strategies. At breathing frequency, CF‐Mu³Gel exhibits a G′ and G″ equal to 24 and 3.2 Pa, respectively. Notably, CF‐Mu³Gel exhibits structural gradients with a gradual reduction of oxygen tension across its thickness (280–194 µmol L⁻¹). Over the culture period, a steep decline in oxygen concentration occurs just a few millimeters below the air–mucus interface in CF‐Mu³Gel, similar to those of CF airway mucus. Importantly, the distinctive features of CF‐Mu³Gel significantly influence bacterial organization and antimicrobial tolerance in mono‐ and co‐cultures of Staphylococcus aureus and Pseudomonas aeruginosa that standard cultures are unable to emulate. The antimicrobial susceptibility determined in CF‐Mu³Gel corroborates the mismatch on the efficacy of antimicrobial treatment between planktonically cultured bacteria and those in patients. With this example‐based research, new light is shed on the understanding of how the substrate influences microbial behavior, paving the way for improved fundamental microbiology studies and more effective drug testing and development.