Review
Engineering, Biomedical
Zhenzhen Zhou, Jianyu He, Yuan Pang, Wei Sun
Summary: Recent advances in tumor microenvironment (TME) modeling and its applications to cancer therapy have led to dramatic changes in the management of multiple malignancies. Various three-dimensional (3D) cell culture techniques have been developed to understand and replicate cancer biology. This review highlights the progress in in vitro 3D TME modeling techniques, such as cell-based, matrix-based, and vessel-based approaches, and their applications in studying tumor-stroma interactions and responses to cancer therapies. The review also addresses the limitations of current TME modeling approaches and proposes new ideas for constructing more clinically relevant models.
Review
Biochemistry & Molecular Biology
Louise Orcheston-Findlay, Samuel Bax, Robert Utama, Martin Engel, Dinisha Govender, Geraldine O'Neill
Summary: The life expectancy of patients with high-grade glioma (HGG) has not improved, highlighting the need for advanced models for future improvement. Currently, advanced models are crucial for identifying new targets and evaluating treatment modalities. While pediatric HGG (pHGG) models lag behind those of adults, there is hope to bring this to light and improve pGBM models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell & Tissue Engineering
Fermin Robledo, Lila Gonzalez-Hodar, Pablo Tapia, Ana-Maria Figueroa, Fernando Ezquer, Victor Cortes
Summary: Researchers successfully extracted multipotent cells from the brown adipose tissue of newborn mice, forming adipose spheroids with complex organoid structure and enhanced leptin secretion upon insulin stimulation. These findings have important implications for the potential therapeutic application of adipose tissue-derived stromal vascular fraction cells.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Multidisciplinary Sciences
Miriam Filippi, Oncay Yasa, Roger Dale Kamm, Ritu Raman, Robert K. Katzschmann
Summary: The next frontier in robotics will be led by biohybrids, and microfluidics is essential for sustaining, improving, and scaling the architectural complexity of biological tissues. Advances in microfluidics have already transformed disease modeling and drug development, and now have the potential to impact regenerative medicine through biohybrids. By combining microfluidics with living materials, tissue perfusion and maturation can be improved, and precise patterning of sensing, processing, and control elements can be achieved.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Robotics
Maria Guix, Rafael Mestre, Tania Patino, Marco De Corato, Judith Fuentes, Giulia Zarpellon, Samuel Sanchez
Summary: Bioinspired hybrid soft robots, which combine living and synthetic components, utilize unique characteristics not found in artificial materials, such as adaptability and response to external stimuli. By optimizing 3D-printed skeleton designs and electrically activating muscle tissue, these robots are able to achieve both swimming and gliding motion mechanisms.
Review
Pharmacology & Pharmacy
Estrella Gonzales-Aloy, Aria Ahmed-Cox, Maria Tsoli, David S. Ziegler, Maria Kavallaris
Summary: Brain cancer is the most deadly cancer and the blood-brain barrier (BBB) poses a challenge for drug delivery. The BBB becomes disrupted in brain cancers, forming the blood-brain tumor barrier (BBTB). 3D cell models have the potential to serve as physiologically relevant in vitro models for studying the BBB and BBTB.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Review
Engineering, Biomedical
Woochan Kim, Yonghyun Gwon, Sunho Park, Hyoseong Kim, Jangho Kim
Summary: Three-dimensional stem cell culture systems have the potential to mimic complex interactions between cells and the extracellular matrix, and have unique properties that can be applied in therapeutics.
BIOACTIVE MATERIALS
(2023)
Review
Biochemistry & Molecular Biology
Shuo Chen, Lijuan Wang, Lei Yang, Abdus Samad Rana, Chuanglong He
Summary: Organoid is an emerging frontier technology in the field of life science, wherein pluripotent stem cells or tissue-derived differentiated/progenitor cells form 3D structures according to their multi-directional differentiation potential and self-assembly ability. This review summarizes the recent development of engineered biomimetic microenvironments for organoids, including the composition of the matrix for organoid culture and strategies for engineering the microenvironment from biophysical, biochemical, and cellular perspectives. The newly developed monitoring technologies are also reviewed, and a brief conclusion and outlook for future research are presented.
MACROMOLECULAR BIOSCIENCE
(2023)
Article
Engineering, Environmental
Yujuan Zhu, Lingyu Sun, Xiao Fu, Junying Liu, Zhenjiang Liang, Hui Tan, Weiping Li, Yuanjin Zhao
Summary: Our multidisciplinary strategy involves engineering vascularized human induced pluripotent stem cells (hiPSCs)-derived brain organoids system with biomimetic features using microfluidic hydrogel microcapsules. The precise fluids control of microfluidic electrospray technology enables the efficient encapsulation of hiPSCs-derived neural cells and formation of uniform human brain organoids. The resulting vascularized brain organoids exhibit structured organization, reasonable tissue size, in vivo-like neural identity, brain region, layered cortex, and complex vascular networks.
CHEMICAL ENGINEERING JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Zheng Ao, Sunghwa Song, Chunhui Tian, Hongwei Cai, Xiang Li, Yifei Miao, Zhuhao Wu, Jonathan Krzesniak, Bo Ning, Mingxia Gu, Luke P. Lee, Feng Guo
Summary: Aging of the immune system influences brain aging and the development of age-related diseases. This study presents the development of a human brain organoid microphysiological analysis platform to investigate immune-driven brain aging. The platform incorporates 3D printing and dynamic rocking flow to model neuroimmune interaction and demonstrates that aged monocytes may drive brain aging. The researchers believe that this platform holds promise for studying aging, neural immunological diseases, autoimmune disorders, and cancer.
Article
Cell Biology
S. Soroush Nasseri, Erika M. J. Siren, Jayachandran N. N. Kizhakkedathu, Karen Cheung
Summary: Three-dimensional cell cultures are increasingly used as in vitro models to mimic in vivo tissues for drug screening. However, the penetration of three-dimensional microscopy techniques is limited by the light scattering of tissues. Traditional tissue clearing protocols are not suitable for small spheroids and organoids. In this study, a novel tissue clearing solution called HyClear was developed for small spheroids and organoids. This protocol allows for one-step tissue clearing and is compatible with high-throughput screening studies.
Review
Chemistry, Multidisciplinary
Guocheng Fang, Yu-Cheng Chen, Hongxu Lu, Dayong Jin
Summary: Multicellular spheroids and organoids are promising models in personalized medicine and drug screening, replicating the structural and functional characteristics of human organs. Microfluidic technology and micro-nano fabrication meet the high requirements of engineering approaches in spheroids and organoids research. This review discusses how spheroids- and organoids-on-a-chip technology facilitates their establishment, expansion, and application through spatial-temporal control, mechanical cues modeling, high-throughput analysis, co-culture, multi-tissue interactions, biosensing, and bioimaging integration. The potential opportunities and challenges in developing spheroids- and organoids-on-a-chip technology are also highlighted.
ADVANCED FUNCTIONAL MATERIALS
(2023)
Article
Neurosciences
Paula Barreras, David Pamies, Thomas Hartung, Carlos A. Pardo
Summary: Microphysiological systems (MPS), including organoids and spheroids, have become valuable tools in studying and modeling neuroinfectious diseases. These systems, derived from induced pluripotent cells or embryonic stem cells, replicate the structural and physiological aspects of the human brain, allowing for the study of viral infections, cell-pathogen interactions, cytopathological effects, and therapeutic compound screening. This review provides an overview of the different methodologies and applications of MPS in studying specific infections such as Zika, Dengue, JC virus, and influenza viruses. It also highlights the limitations and potential of these models in disease modeling and antiviral agent screening.
EXPERIMENTAL NEUROLOGY
(2023)
Review
Pharmacology & Pharmacy
Alexandre Perez-Lopez, Ana Isabel Torres-Suarez, Cristina Martin-Sabroso, Juan Aparicio-Blanco
Summary: The blood-brain barrier (BBB) poses challenges for drug delivery to the central nervous system, resulting in unmet medical needs for brain diseases. Research on the three-dimensional structure of the BBB provides insights into its pathology and aids in the development of novel brain disease therapies. Various 3D models, including hydrogel, spheroid, organoid-based static models, and microfluidic-based BBB-on-a-chip models, have been developed to mimic the human neurovascular unit. This review discusses the development and application of these BBB models for permeability testing of nanomedicines, as well as their advantages and disadvantages, and the validation of their results with in vivo preclinical data.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Article
Chemistry, Multidisciplinary
Minkyu Shin, Taehyeong Ha, Joungpyo Lim, Joohyun An, Geunyoung Beak, Jin-Ha Choi, Ambrose Ashwin Melvin, Jinho Yoon, Jeong-Woo Choi
Summary: A biohybrid robot-on-a-chip based on the human motor system is proposed to evaluate the drug effect on neurodegenerative diseases. The electrophysiological signals from the cerebral organoid induce muscle bundle movement through connected motor neuron spheroids. The drug effect on Parkinson's disease is evaluated by measuring muscle bundle movement.
Article
Physics, Applied
Margherita Ronchini, Milad Zamani, Hai Au Huynh, Yasser Rezaeiyan, Gabriella Panuccio, Hooman Farkhani, Farshad Moradi
Summary: Recent research shows the application of neuromorphic systems in processing biological signals and interfacing with biological tissues, primarily for automatic anomaly detection. This approach lightens the burden on healthcare professionals and enables on-site processing without the need for external processors. The study proposes a neuromorphic device implemented in CMOS technology for the detection of epileptic seizures, demonstrating promising results with low power consumption.
JOURNAL OF PHYSICS D-APPLIED PHYSICS
(2022)
Article
Chemistry, Multidisciplinary
Claudia Lubrano, Ugo Bruno, Chiara Ausilio, Francesca Santoro
Summary: This study investigates the short-term depression of a biomembrane-based organic electrochemical transistor (OECT) through supported lipid bilayer mediation. The ionic barrier behavior of the lipid bilayer is utilized to enhance the neuromorphic operation of the OECT. These biomimetic neuromorphic devices pave the way for in vitro platforms resembling synapses to study and characterize synaptic plasticity loss in neurodegenerative diseases.
ADVANCED MATERIALS
(2022)
Review
Chemistry, Multidisciplinary
Anna Mariano, Claudia Lubrano, Ugo Bruno, Chiara Ausilio, Nikita Bhupesh Dinger, Francesca Santoro
Summary: The plasma membrane is a highly dynamic structure that can stretch, bend, and bud to allow cells to respond and adapt to their environment. Biomimetic strategies based on substrate dimensionality, utilizing conductive polymers, and biofunctionalization through ECM proteins or lipid bilayers have been developed to optimize cell-chip coupling and maximize interfacial interactions.
Article
Biology
Davide Caron, Angel Canal-Alonso, Gabriella Panuccio
Summary: This study suggests that controlling seizure activity by mimicking the temporal dynamics of an anti-ictogenic interictal pattern through electrical stimulation can be an effective and efficient strategy for treating drug-refractory epilepsy. It also highlights the importance of moving towards physiologically meaningful DBS parameters.
Article
Nanoscience & Nanotechnology
Anna Mariano, Claudia Latte Bovio, Valeria Criscuolo, Francesca Santoro
Summary: The development of a functional nervous system depends on interactions between neurons and cues in the neural extracellular matrix (ECM). ECM topographical cues strongly influence neuronal function and behavior. This article discusses how the blueprint of the brain's ECM organization can inspire the design of biomimetic substrates that enhance neural interfaces and control neuronal behavior. Strategies to mimic cell-ECM and cell-cell interactions are explored, including the use of roughness and 3D scaffolds. Anisotropic features such as grooves and fibers can guide neuronal development, while isotropic topographical cues can reproduce neuron-neuron interactions. Advanced techniques like two-photon polymerization and dynamic interfaces are paving the way for smart biointerfaces in neural tissue engineering and repair strategies.
Article
Chemistry, Multidisciplinary
Alice Lunghi, Anna Mariano, Michele Bianchi, Nikita Bhupesh Dinger, Mauro Murgia, Eliana Rondanina, Andrea Toma, Pierpaolo Greco, Michele Di Lauro, Francesca Santoro, Luciano Fadiga, Fabio Biscarini
Summary: This study presents a straightforward approach for fabricating soft interfaces featuring 3D PEDOT:PSS micropillars on a flexible substrate. The 3D micropillars show increased capacitance compared to planar electrodes and support cell adhesion, growth, and influence neurite outgrowth direction. Soft micropillars also act as excellent anchoring loci for elongating neurites, increasing the contact points between cells and electrodes.
ADVANCED MATERIALS INTERFACES
(2022)
Article
Chemistry, Multidisciplinary
Laura Matino, Anna Mariano, Chiara Ausilio, Raghav Garg, Tzahi Cohen-Karni, Francesca Santoro
Summary: The correct wiring of a neural network requires neurons to integrate cues from their extracellular environment, and biologically inspired micro- and nanostructured substrates can regulate axonal outgrowth. Graphene, as a conductive neural interface, has the potential to enhance cell adhesion and neural sprouting. This study found that nanoscale protruding features influenced neuronal growth and branching, and the integrin-mediated contact adhesion points and plasma membrane curvature processes played a crucial role in neurons-to-graphene coupling.
Article
Engineering, Biomedical
Margherita Ronchini, Yasser Rezaeiyan, Milad Zamani, Gabriella Panuccio, Farshad Moradi
Summary: This study introduces a fully-analog neuromorphic device implemented in CMOS technology for analyzing LFP signals in an in vitro model of acute ictogenesis. The developed system can detect ictal and interictal events with ms-latency and with high precision, consuming on average 3.50 nW during the task. The significance of this work lies in paving the way for a new generation of brain implantable devices for personalized closed-loop stimulation for epilepsy treatment.
JOURNAL OF NEURAL ENGINEERING
(2023)
Article
Chemistry, Multidisciplinary
Anna Mariano, Ines Fasolino, Nikita Bhupesh Dinger, Claudia Latte Bovio, Irene Bonadies, Alessandro Pezzella, Luigi Ambrosio, Maria Grazia Raucci, Francesca Santoro
Summary: During neural system development, neurons respond to cues found in the brain's environment, and these cues have been used in neural tissue engineering to create scaffolds that can guide neuronal behavior. Anisotropic aligned fibers, mimicking natural fiber structures, have proven effective in promoting cell alignment and neuronal differentiation. Melanins, including eumelanin, possess beneficial properties and have been used as coatings. Aligned poly(lactic acid) fibers coated with eumelanin promote cell alignment, morphology, and maturation of neuroblastoma cells.
ADVANCED MATERIALS INTERFACES
(2023)
Article
Materials Science, Multidisciplinary
Giovanni Maria Matrone, Ugo Bruno, Csaba Forro, Claudia Lubrano, Stefano Cinti, Yoeri van de Burgt, Francesca Santoro
Summary: Researchers have developed an electrochemical neuromorphic organic device (ENODe) that functions as an artificial synapse, emulating neurotransmitter transmission and modulation while overcoming electrochemical and readout interferences. The platform replicates high-level biological processes and holds promise for tissue-integrated neuromorphic systems.
ADVANCED MATERIALS TECHNOLOGIES
(2023)
Article
Engineering, Biomedical
Davide Caron, Stefano Buccelli, Angel Canal-Alonso, Javad Farsani, Giacomo Pruzzo, Bernabe Linares Barranco, Juan Manuel Corchado, Michela Chiappalone, Gabriella Panuccio
Summary: The objective of this study is to evaluate the efficacy and robustness of an artificial bridge in controlling ictogenesis and restoring the functional connectivity of the hippocampal loop in the treatment of epilepsy. The main results show that the bridge significantly decreased or prevented ictal activity and recovered the functional connectivity of the hippocampal loop. The significance of this work lies in its potential to shift the conceptual design of stimulation devices for epilepsy treatment towards functional restoration of brain circuits.
JOURNAL OF NEURAL ENGINEERING
(2023)
Article
Engineering, Electrical & Electronic
Ugo Bruno, Anna Mariano, Daniela Rana, Tobias Gemmeke, Simon Musall, Francesca Santoro
Summary: The computation of the brain relies on efficient communication among neurons. Efforts to leverage brain-inspired principles have led to the introduction of artificial neural networks, and researchers are now exploring novel solutions to emulate specific brain features. The development of neurohybrid systems that integrate silicon-based and organic electronics-based technologies may enable bidirectional communication between biological and artificial brains, offering potential therapeutic applications and advancements in prosthetics.
NEUROMORPHIC COMPUTING AND ENGINEERING
(2023)
Meeting Abstract
Cell & Tissue Engineering
Natalia Gostynska, Giulia Della Rosa, John Wesley Ephraim, Monica Moroni, Gabriella Panuccio, Nicola Tirelli, Gemma Palazzolo
TISSUE ENGINEERING PART A
(2022)
Article
Materials Science, Biomaterials
Matteo Battaglini, Alessio Carmignani, Chiara Martinelli, Jamila Colica, Attilio Marino, Stefano Doccini, Valentina Mollo, Francesca Santoro, Martina Bartolucci, Andrea Petretto, Filippo Maria Santorelli, Gianni Ciofani
Summary: This study evaluated the effects of polydopamine nanoparticles (PDNPs) on human fibroblasts derived from patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) in terms of antioxidant properties and protein expression. The results showed that PDNPs can partially counteract ROS-induced damages in ARSACS patient-derived fibroblasts.
BIOMATERIALS SCIENCE
(2022)
Article
Engineering, Electrical & Electronic
Dennis Christensen, Regina Dittmann, Bernabe Linares-Barranco, Abu Sebastian, Manuel Le Gallo, Andrea Redaelli, Stefan Slesazeck, Thomas Mikolajick, Sabina Spiga, Stephan Menzel, Ilia Valov, Gianluca Milano, Carlo Ricciardi, Shi-Jun Liang, Feng Miao, Mario Lanza, Tyler J. Quill, Scott T. Keene, Alberto Salleo, Julie Grollier, Danijela Markovic, Alice Mizrahi, Peng Yao, J. Joshua Yang, Giacomo Indiveri, John Paul Strachan, Suman Datta, Elisa Vianello, Alexandre Valentian, Johannes Feldmann, Xuan Li, Wolfram H. P. Pernice, Harish Bhaskaran, Steve Furber, Emre Neftci, Franz Scherr, Wolfgang Maass, Srikanth Ramaswamy, Jonathan Tapson, Priyadarshini Panda, Youngeun Kim, Gouhei Tanaka, Simon Thorpe, Chiara Bartolozzi, Thomas A. Cleland, Christoph Posch, Shihchii Liu, Gabriella Panuccio, Mufti Mahmud, Arnab Neelim Mazumder, Morteza Hosseini, Tinoosh Mohsenin, Elisa Donati, Silvia Tolu, Roberto Galeazzi, Martin Ejsing Christensen, Sune Holm, Daniele Ielmini, N. Pryds
Summary: This article introduces the characteristics and advantages of von Neumann architecture and neuromorphic computing systems. While traditional von Neumann architecture is powerful, it has high power consumption and cannot handle complex data. Neuromorphic computing systems, inspired by biological concepts, can achieve lower power consumption for storing and processing large amounts of digital information. The aim of this article is to provide perspectives on the current state and future challenges in the field of neuromorphic technology, and to provide a concise yet comprehensive introduction and future outlook for readers.
NEUROMORPHIC COMPUTING AND ENGINEERING
(2022)