Mechanobiology in Medicine最新文献

Mechanotransduction, the transfer of mechanical stimuli into various biological signals, is a vital biological process in multiple organ systems. The osteoclast (OC) plays a vital role in bone metabolism and repair. The role of mechanotransduction in osteoclasts and other bone cells is emerging. This commentary highlights a recent research report on a novel strategy for the precise regulation of OC formation via modulating matrix stiffness. Modulation of the mechanotransduction pathways in the skeletal system will pave the way for the development of a matrix stiffness-based strategy for bone tissue regeneration.

Mechanobiology is the study of how mechanical forces affect biological systems, including cells and tissues. The two-photon lithography (TPL) as a powerful 3D printing technique allows the creation of 3D complex structures at a microscopic scale. By applying the TPL into the mechanobiology studies, researchers could create precise structures that mimic the mechanical properties of biological system, allowing for the study of mechanobiological processes in a controlled environment. This implies applications in tissue engineering, drug screening, and fundamental research into the mechanisms of mechanobiology. In this review, we highlight recent advances in TPL for mechanobiology studies, as well as the potential future directions for this promising field.

Mechanobiology is an interdisciplinary discipline combining biology, engineering, chemistry, physics, and medicine. Mechanobiology research comprehensively discusses, the role of mechanical factors in various life processes and the occurrence and development of associated and diseases at the whole organism, organ, cell, protein and gene levels. The cellular and molecular mechanisms of mechanical signal transduction and response are elucidated, in addition to the discovery of novel biomarkers and potential drug targets, which are mechanosensitive molecules. This paper reviews the development of mechanobiology research in China since the new century, while focusing on the research achievements of Chinese scientists in the field of mechanobiology over the last three years, including cardiovascular, bone and joint, tumor, cellular, and molecular mechanobiology. Meanwhile, it has been suggested that in the future, mechanobiology research should include are indicated detailed studies on the mechanobiological mechanism of diseases at the cellular and molecular levels firstly, so that the newly discovered biomarkers or potential targets can gradually achieve clinical transformation. Second, future research should strengthen the qualitative and quantitative combination of biological experiments and mechanical and mathematical modeling analyses, especially at cellular, subcellular and molecular scales. Mechanobiological studies are of great theoretical and practical significance for our understanding of the mechanical mechanisms and natural laws of growth and senility of the human body, expounding pathological mechanisms of diseases, and researching and developing new medicines and technologies to promote biomedical and clinical research for human health.

Dysfunctions of calcium cycling occur in heart failure with reduced and preserved ejection fraction (HFrEF and HFpEF). HFrEF and HFpEF showed Ca²⁺ leakage at diastole. The compensation of Na⁺/Ca²⁺ exchanger and the decrease of T-tubule density reduces cytoplasmic Ca²⁺ concentration in HFrEF and impairs systolic function. In contrast, HFpEF has the increase of cytoplasmic Ca²⁺ concentration and diastolic dysfunctions. The decrease of mitochondrial Ca²⁺ concentration weakens myocardial contractility in HFrEF while the increased concentration retains the contractility in HFpEF. Here, the changes of calcium cycling in HFrEF and HFpEF are summarized and the possibility of relevant therapeutic targets is discussed.

Given the tremendous increase in the risks of cartilage defects in the sports and aging population, current treatments are limited, and new repair strategies are needed. Cartilage tissue engineering (CTE) is a promising approach to handle this burden and several fabrication technologies and biomaterials have been developed these years. The extracellular matrix (ECM) of cartilage consists of a tissue-specific 3D microenvironment with excellent biomechanical and biochemical properties, which regulates cell proliferation, adhesion, migration, and differentiation, thus attracting a great deal of attention to the rapid development of CTE based on ECM components. New generations of biomaterials are being developed rapidly for use as scaffolds to mimic the natural ECM environment. In this review, we discuss such CTE scaffolds based on ECM-derived biomaterials by reviewing the biomaterials for CTE, the applications in different scaffolds and their processing approaches, as well as the current clinical applications of those ECM-based CTE scaffolds.

ChatGPT has garnered significant attention for its impressive capabilities across various domains, including medicine and mechanobiology. In order to facilitate the integration of ChatGPT into research, this paper explores the applications of ChatGPT in these domains, focusing on its usage in (1) reading and writing, (2) retrieval and knowledge management, and (3) computation, simulation, and visualization. Meanwhile, this study acknowledges the limitations and challenges associated with ChatGPT's usage. We investigate the interaction between ChatGPT and external tools in these applications and advocate for the integration of more powerful tools in these research areas into ChatGPT to further expand its potential applications in medicine and mechanobiology.

The use of mechanical biology and biomechanical signal transduction is a novel approach to attenuate biological tissue degeneration, whereas the understanding of specific cellular responses is critical to delineate the underlying mechanism. Dynamic mechanical signals with optimized loading signals, i.e., intensity and frequency, have been shown to have the potential to regulate adaptation and regeneration. Mechanotransduction pathways are of great interest in elucidating how mechanical signals produce such observed effects, including reduced tissue mass loss, increased healing and formation, and cell differentiation. While mechanobiology in the adaptation of cells and tissues is observed and recorded in the literature, its application in disease mechanism and treatment is under development. We would congratulate the opening of the Mechanobiology in Medicine journal, which provides an effective platform for advanced research in basic mechanotransduction and its translation in disease diagnosis, therapeutics, and beyond. This review aims to develop a cellular and molecular understanding of the mechanotransduction processes in tissue regeneration, which may provide new insights into disease mechanisms and the promotion of healing. Particular attention is allotted to the responses of mechanical loading, including potential cellular and molecular pathways, such as mechanotransduction associated with mechanotransduction pathways (e.g., Piezo ion channels and Wnt signaling), immune-response, neuron development, tissue adaptation and repair, and stem cell differentiation. Altogether, these discussed data highlight the complex yet highly coordinated mechanotransduction process in tissue regeneration.

Tumor progression is accompanied by complex structural changes in the extracellular matrix (ECM), which decrease the effective exposure of tumors to drugs. Breast cancer are highly heterogeneous with a typically high degree of ECM remodeling and stiffening. Therefore, it is especially important to explore the influence of ECM stiffness on breast cancer chemotherapy. Here, we fabricated 3D Methacrylate Gelatin (GelMA) hydrogels with varying stiffness by photo-crosslinking to simulate the change of tissue stiffness during the development of breast cancer. These 3D hydrogels were used to evaluate how MDA-MB-231 cells responded to the chemotherapy drug doxorubicin (DOX), the mechanical regulatory mechanism involved has also been investigated. The findings demonstrated that 15% GelMA hydrogel (9 ​kPa) increased the activity of EGFR to block the Hippo signaling pathway and activate Yes-associated protein (YAP). Activated YAP allowed cytosolic EGFR transport into the nucleus via binding with it, up-regulated the expression of their respective transcriptional targets, and thus generates drug resistance. Altogether, our study implicates that stiffness-dependent EGFR activation plays an important role in breast cancer drug resistance, indicating that targeting of both YAP and EGFR signals may present a promising therapeutic strategy for ECM stiffness-induced drug resistance.

Tumor models in vitro are conventional methods for developing anti-cancer drugs, evaluating drug delivery, or calculating drug efficacy. However, traditional cell line-derived tumor models are unable to capture the tumor heterogeneity in patients or mimic the interaction between tumors and their surroundings. Recently emerging patient-derived preclinical cancer models, including of patient-derived xenograft (PDX) model, circulating tumor cell (CTC)-derived model, and tumor organoids-on-chips, are promising in personalized drug therapy by recapitulating the complexities and personalities of tumors and surroundings. These patient-derived models have demonstrated potential advantages in satisfying the rigorous demands of specificity, accuracy, and efficiency necessary for personalized drug therapy. However, the selection of suitable models is depending on the specific therapeutic requirements dictated by cancer types, progressions, or the assay scale. As an example, PDX models show remarkable advantages to reconstruct solid tumors in vitro to understand drug delivery and metabolism. Similarly, CTC-derived models provide a sensitive platform for drug testing in advanced-stage patients, while also facilitating the development of drugs aimed at suppressing tumor metastasis. Meanwhile, the demand for large-scale testing has promoted the development of tumor organoids-on-chips, which serves as an optimal tool for high-throughput drug screening. This review summarizes the establishment and development of PDX, CTC-derived models, and tumor organoids-on-chips and addresses their distinctive advantages in drug discovery, sensitive testing, and screening, which demonstrate the potential to aid in the selection of suitable models for fundamental cancer research and clinical trials, and further developing the personalized drug therapy.