Sensing the mechanical properties of the substrates or the matrix by the cells and the tissues, the subsequent downstream responses at the cellular, nuclear and epigenetic levels and the outcomes are beginning to get unraveled more recently. There have been various instances where researchers have established the underlying connection between the cellular mechanosignalling pathways and cellular physiology, cellular differentiation, and also tissue pathology. It has been now accepted that mechanosignalling, alone or in combination with classical pathways, could play a significant role in fate determination, development, and organization of cells and tissues. Furthermore, as mechanobiology is gaining traction, so do the various techniques to ponder and gain insights into the still unraveled pathways. This review would briefly discuss some of the interesting works wherein it has been shown that specific alteration of the mechanical properties of the substrates would lead to fate determination of stem cells into various differentiated cells such as osteoblasts, adipocytes, tenocytes, cardiomyocytes, and neurons, and how these properties are being utilized for the development of organoids. This review would also cover various techniques that have been developed and employed to explore the effects of mechanosignalling, including imaging of mechanosensing proteins, atomic force microscopy (AFM), quartz crystal microbalance with dissipation measurements (QCMD), traction force microscopy (TFM), microdevice arrays, Spatio-temporal image analysis, optical tweezer force measurements, mechanoscanning ion conductance microscopy (mSICM), acoustofluidic interferometric device (AID) and so forth. This review would provide insights to the researchers who work on exploiting various mechanical properties of substrates to control the cellular and tissue functions for tissue engineering and regenerative applications, and also will shed light on the advancements of various techniques that could be utilized to unravel the unknown in the field of cellular mechanobiology. 

/pdf/trends-in-mechanobiology-guided-tissue-engineering-and-tools-38o2osx3.pdf

Trends in mechanobiology guided tissue engineering and tools to study cell-substrate interactions: a brief review

The in-depth intersection between nanoscience and oncology comes from the fact that nanomaterials are in a similar dimension to basic biomolecules. Drug delivery systems (DDSs), which are either targeted to a particular site and are intended for the controlled release in a particular position, have been studied extensively at the nanoscale and are by far, the most advanced technology in the area of nanoparticle applications. This, consequently lead to the improvement and development of convenient administration routes, lower toxicity, fewer side effects, and extended drug life cycle. Carbon nanomaterials (CNMs) with favorable size and unique fluorescence properties, which was considered an ideal candidate to transport or deliver therapeutic drugs to specific targets in a controlled manner. The development of DDSs based on them constitutes an interesting topic in highly effective and universal therapies to achieve better therapeutic outcomes and reduce the side effects of malignancies. In this review, the cutting-edge progress of CNMs in DDSs was comprehensively summarized. Additionally, the emphasis was placed on the applications of CNMs including fullerene, graphene, carbon nanotubes (CNTs), carbon dots (CDs), and nano-diamonds (NDs) in drug delivering. Further, we gave some insights into the future direction and foreseeable challenges of DDSs based on CNMs used in cancer therapy, which we hope these inspirations in DDSs associated with anti-cancer therapy will provide perspectives in designing new drugs for further tumor treatment.

Current Advances and Prospects in Carbon Nanomaterials-Based Drug Delivery Systems for Cancer Therapy.

Analysis of nanomaterial biocoronas in biological and environmental surroundings

Organoids are stem cell-derived, self-organizing, 3D structures. Compared to the conventional 2D cell culture method, 3D cultured organoids contain a variety of cell types that can form functional “micro-organs” and can be used to simulate the occurrence process and physiological pathological state of organ tissues more effectively. Nanomaterials (NMs) are becoming indispensable in the development of novel organoids. Understanding the application of nanomaterials in organoid construction can, therefore, provide researchers with ideas for the development of novel organoids. Here, we discuss the application status of NMs in various organoid culture systems and the research direction of NMs combined with organoids in the biomedical field.

Intersection of nanomaterials and organoids technology in biomedicine

Ferroptosis is a vital driver of pathophysiological consequences of Alzheimer's disease (AD). High-efficiency pharmacological inhibition of ferroptosis requires comprehensive coordination of diverse abnormal intracellular events, which is an urgent problem and great challenge for its application in AD treatment. Herein, a triphenylphosphonium-modified quercetin-derived smart nanomedicine (TQCN) is developed for multipronged anti-ferroptosis therapy in AD. Taking advantage of the favorable brain-targeting and mitochondria-locating properties, TQCN can efficiently chelate iron through phytopolyphenol-mediated spontaneous coordination and self-assemble into metal-phenolic nanocomplexes in situ, exerting escalating exogenous offensive effects to attenuate iron overload and its induced free radical burst. Meanwhile, the Nrf2 signaling-mediated endogenous defensive system is reconstituted to restore iron metabolism homeostasis represented by iron export and storage and enhance cytoprotective antioxidant cascades represented by lipid peroxidation detoxification. Benefiting from the multifaceted regulation of pathogenic processes triggering ferroptosis, TQCN treatment can ameliorate various neurodegenerative manifestations associated with brain iron deposition and rescue severe cognitive decline in AD mice. This work displays great promise of in situ self-assembled phytopolyphenol-coordinated intelligent nanotherapeutics as advanced candidates against ferroptosis-driven AD progression.

In Situ Self-Assembled Phytopolyphenol-Coordinated Intelligent Nanotherapeutics for Multipronged Management of Ferroptosis-Driven Alzheimer's Disease.

The biological effect of engineered carbon nanotubes (CNTs) as beneficial biomaterials on the intestine, especially on its development, remains unclear. Here, we investigated the profitable effect of CNTs with a different graphene layer and surface modification on the 3D model of intestinal organoids and demonstrated that CNTs (50 μg/mL) promoted the development of intestinal organoids over time (0-5 days). The mechanisms involve the modulation of extracellular matrix (ECM) viscoelasticity and intracellular energy metabolism. In particular, CNTs reduced the hardness of the extracellular matrix through decreasing the elasticity and increasing the viscosity as a result of elevated metalloproteinase and binding to a protein scaffold, which activated the mechanical membrane sensors of cells, Piezo, and downstream P-p38-yes-associated protein (YAP) pathway. Moreover, CNTs altered the metabolic profile of intestinal organoids and induced increased mitochondria activity, respiration, and nutrient absorption. These mechanisms cooperated with each other to promote the proliferation and differentiation of intestinal organoids. In addition, the promoted effect of CNTs is highly dependent on the number of graphene layers, manifested as multiwalled CNTs > single-walled CNTs. Our findings highlight the CNT-intestine interaction and imply the potential of CNTs as biomaterials for intestine-associated tissue engineering.

Carbon Nanotubes Promote the Development of Intestinal Organoids through Regulating Extracellular Matrix Viscoelasticity and Intracellular Energy Metabolism.

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Carbon Nanotubes Promote the Development of Intestinal Organoids through Regulating Extracellular Matrix Viscoelasticity and Intracellular Energy Metabolism.