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Stem cell regenerative potential owing to the capacity to self-renew as well as differentiate into other cell types is a promising avenue in regenerative medicine. Stem cell niche not only provides physical scaffolding but also possess instructional capacity as it provides a milieu of biophysical and biochemical cues. Extracellular matrix (ECM) has been identified as a major dictator of stem cell lineage, thus understanding the structure of in vivo ECM pertaining to specific tissue differentiation will aid in devising in vitro strategies to improve the differentiation efficiency. In this review, we summarize details about the native architecture, composition and mechanical properties of in vivo ECM of the early embryonic stages and the later adult stages. Native ECM from adult tissues categorized on their origin from respective germ layers are discussed while engineering techniques employed to facilitate differentiation of stem cells into particular lineages are noted. Overall, we emphasize that in vitro strategies need to integrate tissue specific ECM biophysical cues for developing accurate artificial environments for optimizing stem cell differentiation.

The extracellular matrix (ECM) is a dynamic and highly organized tissue structure, providing support and maintaining normal epithelial architecture. In the last decade, increasing evidence has emerged demonstrating that alterations in ECM composition and assembly strongly affect cellular function and behavior. Even though the detailed mechanisms underlying cell-ECM crosstalk are yet to unravel, it is well established that ECM deregulation accompanies the development of many pathological conditions, such as gastric cancer. Notably, gastric cancer remains a worldwide concern, representing the third most frequent cause of cancer-associated deaths. Despite increased surveillance protocols, patients are usually diagnosed at advanced disease stages, urging the identification of novel diagnostic biomarkers and efficient therapeutic strategies. In this review, we provide a comprehensive overview regarding expression patterns of ECM components and cognate receptors described in normal gastric epithelium, pre-malignant lesions, and gastric carcinomas. Important insights are also discussed for the use of ECM-associated molecules as predictive biomarkers of the disease or as potential targets in gastric cancer.

Extracellular matrix (ECM) is a dynamic, three‐dimensional network that provides structural support and regulates key biological processes, including cell adhesion, migration, differentiation, and signal transduction. Its mechanical properties, such as stiffness, topology, and viscoelasticity, are crucial in normal and pathological conditions, influencing cell behavior through mechanotransduction pathways. Dysregulation of ECM is linked to various diseases, making a thorough understanding of its composition and properties essential. This review discusses ECM composition, physical properties, and the limitations of in vitro ECM models. It highlights the role of ECM in tissue homeostasis, particularly in regulating cell behavior via mechanotransduction, focusing on force‐sensitive sensors like integrins, Piezo1, TRPV4, and YAP/TAZ. Additionally, the review explores ECM remodeling in cancer, fibrosis, and cardiovascular diseases, along with current therapeutic strategies targeting ECM components, such as nanotechnology‐based therapies, small molecule inhibitors, and CAF‐targeted therapies. Challenges and clinical applications of these therapies are also discussed. Finally, the review looks ahead to future research, emphasizing the integration of ECM‐targeted therapies in precision medicine and novel approaches to normalizing ECM composition and structure for therapeutic benefits. This review provides mechanobiological insights into therapeutic strategies targeting the ECM. Targeting ECM dysregulation: therapeutic strategies for disease intervention. Dysregulated ECM composition and biomechanics contribute to disease pathogenesis in cancer and fibrotic disorders. Physical modulation: Nanomedicine‐based strategies tune ECM physical properties (e.g., density, stiffness) to enhance drug penetration and therapeutic efficacy in the TME. Molecular targeting: Small‐molecule drugs selectively modify ECM components to induce angiogenesis, immune response, and tissue remodeling. Cellular reprogramming: Pharmacological intervention of CAF signaling pathways promotes functional normalization, thereby restoring ECM homeostasis.

Cells respond to both chemical and mechanical cues present within their microenvironment. Various mechanical signals are detected by and transmitted to the cells through mechanoreceptors. These receptors often contact with the extracellular matrix (ECM), where the external signals are converted into a physiological response. Integrins are well-defined mechanoreceptors that physically connect the actomyosin cytoskeleton to the surrounding matrix and transduce signals. Families of α and β subunits can form a variety of heterodimers that have been implicated in cancer progression and differ among types of cancer. These heterodimers serve as the nexus of communication between the cells and the tumor microenvironment (TME). The TME is dynamic and composed of stromal cells, ECM and associated soluble factors. The most abundant stromal cells within the TME are cancer-associated fibroblasts (CAFs). Accumulating studies implicate CAFs in cancer development and metastasis through their remodeling of the ECM and release of large amounts of ECM proteins and soluble factors. Considering that the communication between cancer cells and CAFs, in large part, takes place through the ECM, the involvement of integrins in the crosstalk is significant. This review discusses the role of integrins, as the primary cell-ECM mechanoreceptors, in cancer progression, highlighting integrin-mediated mechanical communication between cancer cells and CAFs.

Biomaterial choice is an essential step during the development tissue engineering and regenerative medicine (TERM) applications. The selected biomaterial must present properties allowing the physiological-like recapitulation of several processes that lead to the reestablishment of homeostatic tissue or organ function. Biomaterials derived from the extracellular matrix (ECM) present many such properties and their use in the field has been steadily increasing. Considering this growing importance, it becomes imperative to provide a comprehensive overview of ECM biomaterials, encompassing their sourcing, processing, and integration into TERM applications. This review compiles the main strategies used to isolate and process ECM-derived biomaterials as well as different techniques used for its characterization, namely biochemical and chemical, physical, morphological, and biological. Lastly, some of their applications in the TERM field are explored and discussed. [Display omitted] •The main methods for ECM isolation from tissue, organs, and cells and subsequent decellularization are reviewed.•Techniques for its biochemical, physical, morphological and biological characterization are described.•Examples of the application of ECM-derived biomaterials are briefly compiled and discussed.•Future focal points of research related with ECM-derived biomaterials are anticipated.

Electrochemical machining (ECM) is a contemporary electrochemical energy-based machining practice that has widely been attempted for the productive processing of a vast range of typical engineering materials, namely, composites and difficult-to-process advanced materials. In the present work, an attempt has been made to critically review and report the previously investigated studies and research in the domain of machining numerous materials with electrochemical machining and its other allied methods. This work also deeply explores the various theoretical, experimental, modeling-based, and optimization-related research studies carried out in the broad domain of ECM for finding out the most effective and conclusive outcomes with the overall process improvement with the support and quality selection of machine, tool materials, electrolyte flow, and some other operating parameters. While shifting from macro- to micro-electrochemical machining, numerous investigations have been reported in the literature that have been targeted to enhance the overall machining performance and the measures. Among the numerous acquirable modifications in assisted ECM as employed in research and developments and industries, vibration-assisted ECM has been revealed as a more sturdily established ECM variation as compared to other explored versions such as abrasive Jet-ECM, magnetic-assisted ECM, and laser-assisted ECM. Furthermore, the in-depth discussion about jet-assisted ECM and wire ECM has also been reported, along with the considerations of several impactful process inputs. The concluding section of this article explores the several developments made in wire and micro-ECM processes and layouts the issues and directions for further research.

Comparing the prediction effects of traditional econometric algorithm model and deep learning algorithm model, taking regional GDP as an example, two prediction models of ARMA-ECM and LSTM-SVR are established for prediction, and the prediction results of different models are compared and analyzed. The results show that there are some deviations in the prediction results of the two models, but the prediction trends are the same. The prediction accuracy of LSTM-SVR model will decrease significantly with the reduction of time series data samples, while ARMA-ECM model is not so sensitive.

Metastasis of cancer cells to the brain leads to a poor prognosis in patients with cancer. The brain environment is characterized by cell types, extracellular matrices (ECMs), and mechanical properties that differ from those of the primary tumors. A previous study using human melanoma cells (WM266.4 cells) and its highly brain-metastatic subline cells (WM266.4-BrM3 cells) revealed that WM266.4-BrM3 cells showed enhanced proliferation in brain tissues after cardiac injection in mice compared with WM266.4 cells. However, the effects of mechanical properties such as ECM stiffness on growth and gene expression in WM266.4-BrM3 cells remain to be clarified. In this study, we cultured these cells on ECMs of different stiffnesses. On a soft ECM, WM266.4-BrM3 cells showed significantly higher proliferation and lower expression of early growth response 1 (EGR1) and TP53 than WM266.4 cells. In contrast, on a stiff ECM, the proliferation and EGR1 expression of WM266.4 and WM266.4-BrM3 cells were not significantly different. Additionally, EGR1 knockdown by siRNA transfection in WM266.4 cells results in promoted cell proliferation and downregulated TP53 on a soft ECM. These results suggest that brain metastatic WM266.4 cells decrease EGR1 expression, thereby promoting cell proliferation via TP53 downregulation on a soft ECM.Key words: EGR1, ECM stiffness, metastasis, cancer, growth

•Deregulation of ECM (i.e., desmoplastic ECM alignment) alters tumorigenesis.•Both biomechanical and biochemical factors promote desmoplastic ECM formation.•Cell–ECM ‘dynamic reciprocity’ is regulated by integrins and Rho–ROCK. The extracellular matrix (ECM) provides structural and biochemical signals that regulate cell function. A well-controlled balance between cells and surroundings (i.e., dynamic reciprocity) is crucial for regulating ECM architecture. During cancer progression, epithelial cells undergo genetic alterations which, together with stromal changes including ECM remodeling, disturb the homeostatic dynamics of the epithelium. A parallel organization of stromal ECM fibrils is associated with tumorigenic responses. In an emerging paradigm, continuous and progressive regulation via mechanical forces and aberrant signaling are believed to be responsible for tumor-associated ECM remodeling. In this review we discuss the discrete biomechanical and biochemical mechanisms that underlie these architectural changes and highlight their particular relevance to the regulation of the alignment of ECM in the mesenchymal stroma.

The importance of stem cell growth and its fate is highly essential for the use of stem cells in therapy and regeneration. There are conflicting evidences regarding the actual role of stem cells when injected into a patient towards damage recovery and its lifespan inside the body. Tumor microenvironment differs from that of normal cells and may have a role in the growth of stem cells when associated with them. In cancer, the uncontrolled growth of cells remodels the extracellular matrix (ECM). The ECM alteration occurs as the mutated fibroblast cells release growth factors into the ECM which further alters the ECM directly or changes the epithelial cells and then alters the ECM. In this review we will discuss about the components and functions of ECM and how does it differ in cancer cells compared to normal cells. Abnormal dynamics of the ECM and its role in cancer progression will also be discussed.