Mechanobiology in Medicine最新文献

A recent study published in Nature Communications presents a unique approach using an osteoinductive intramedullary (IM) implant as an adjunctive therapy for bone transport distraction osteogenesis. The study demonstrates that this innovative technique achieves early bony bridging, eliminates pin tract infections, and prevents docking site non-union, offering significant potential for the treatment of large bone defects. The study also highlights an additive effect of the osteoinductive IM implant on distraction osteogenesis for managing bone defect.

A recent study published in Science Advances¹ showed the influence of Yap on notochord formation and NT (neural tube) patterning in vertebrate embryonic development, and conducted an in-depth study from the perspective of biomechanical signal mechanotransduction. In addition, this study also explored the possible complex interaction between mechanical signals and gene expression. Together, this study provides new insights into the development mechanism of early vertebrate embryos.

The implantation of foreign materials often leads to fibroblast activation and fibrous capsule formation. The process of fibroblast-to-myofibroblast transition (FMT) is partially influenced by the surface properties of biomaterials, including factors such as stiffness, wettability, roughness, and topography. This article reviews the studies that concentrate on the connection between the topographical cues of biomaterials and FMT. We have summarized the key findings and subsequently analyzed the potential reasons behind the contradictory conclusions in these studies.

The mechanical constraints in the overcrowding glioblastoma (GBM) microenvironment have been implicated in the regulation of tumor heterogeneity and disease progression. Especially, such mechanical cues can alter cellular DNA transcription and give rise to a subpopulation of tumor cells called cancer stem cells (CSCs). These CSCs with stem-like properties are critical drivers of tumorigenesis, metastasis, and treatment resistance. Yet, the biophysical and molecular machinery underlying the emergence of CSCs in tumor remained unexplored. This work employed a two-dimensional micropatterned multicellular model to examine the impact of mechanical constraints arisen from geometric confinement on the emergence and spatial patterning of CSCs in GBM tumor. Our study identified distinct spatial distributions of GBM CSCs in different geometric patterns, where CSCs mostly emerged in the peripheral regions. The spatial pattern of CSCs was found to correspond to the gradients of mechanical stresses resulted from the interplay between the cell-ECM and cell–cell interactions within the confined environment. Further mechanistic study highlighted a Piezo1-RhoA-focal adhesion signaling axis in regulating GBM cell mechanosensing and the subsequent CSC phenotypic transformation. These findings provide new insights into the biophysical origin of the unique spatial pattern of CSCs in GBM tumor and offer potential avenues for targeted therapeutic interventions.

Mechanical force often has clear effects on tissue niche remodeling. However, the changes in stem cells and their roles in clinical treatment remain unclear. Orthodontic tooth movement (OTM), the primary approach to treating dental-maxillofacial malformations, involves reconstruction of periodontal tissue. Herein, lineage tracing revealed that Col1⁺ cells are distributed in the periodontal ligament and are sensitive to mechanical forces during OTM. Immunofluorescence analysis confirms that Col1⁺ cells can differentiate into osteoblasts and fibroblasts under orthodontic force. Moreover, Col1⁺ cells may be involved in angiogenesis. These findings suggest that Col1⁺ cells play a crucial role in the mechanical remodeling of periodontal tissue during OTM and may serve as a valuable tool for studying the mechanism of OTM.

The mechanical microenvironment strongly affects cell state and decisions. Cell mechanosensing has been described by a molecular clutch which gets progressively engaged depending upon the stiffness of the extracellular material. Through the actuation of pulling forces exerted by actin fibres on the mechanosensitive talin-integrin molecular complex, cells sense and react to the stiffness of their surroundings. However, whether the truly cell mechanosensing is regulated by the pure elastic stiffness or by the strain energy density of the ECM is still debated. Here we report that the cell response to change of strain energy density out of loading induced deformation (purely elastic) can be accounted for by including, within the same frame of the molecular clutch model, the residual strain/stress to which the ECM could be subjected before establishing any interaction with the molecular clutches. To include the contribution of residual stresses, an additional spring orthogonal to the ones already present in the original clutch model has been introduced; this spring takes memory of the ECM strain energy when axially deformed before any interaction with cell molecular clutches can occur. To evaluate the influence of strain on the optimum number of clutches, the model has been implemented with different levels of strain. Results suggest that cells undergo a reinforcement process, stiffening the cytoskeleton in response to the ECM stress/strain energy.

Covalent organic frameworks (COFs) are emerging crystalline porous materials composed of covalently linked and periodically arranged organic molecules, which exhibit mechanical properties mediated by structural diversity. Meanwhile, the tunable mechanical properties of COFs have been widely applied in drug delivery and cancer therapy. Herein, we first summarize the regulation strategies of COFs with different mechanical strengths, such as structural dimensions, pore sizes, and host–guest interaction forces. Then, the remarkable achievements of COFs with different mechanical properties in drug delivery and cancer therapy in recent years are introduced. Finally, the mechanical strength regulation of COFs and the remaining challenges for biomedical applications are presented. This review provides a more comprehensive understanding of the application of COFs systems with tunable mechanical properties in the field of biomedicine, and promotes the development of interdisciplinary research between COFs materials and nanomedicine.

A recent study published in Cell Stem Cell [1] showed that matrix stiffness critically regulates hematopoietic stem cell (HSC) niche, and successfully engineered a soft bone marrow (BM) organoid to maintain and rejuvenate HSCs ex vivo. In addition, BM stiffening was also identified as a novel aging hallmark of the hematopoietic system. Together, these important findings implicate matrix stiffness as a fundamental biomechanical factor governing cell fate determination and aging of tissue-specific stem cells.

We have shown that platelet-derived microvesicles (PMVs) induce abnormal proliferation, migration, and energy metabolism of vascular smooth muscle cells (VSMCs) after vascular intimal injury. Here, we examined a novel role of podosome in mediating matrix metalloproteinase-9 (MMP-9) dependent VSMC migration induced by platelet-derived microvesicles (PMVs). VSMCs were isolated from the thoracic aortas of male Sprague Dawley (SD) rats and identified with immunofluorescent staining. Blood samples were collected from SD Rats, the platelets were isolated with density gradient centrifugation from the blood samples and activated by collagen I. Intriguingly, proteins expressed in platelets were found to participate in the positive regulation of podosome assembly using GO analysis by DAVID, and most of the proteins were found in extracellular exosomes. Of note, activated platelets indirectly induced VSMC migration via releasing PMVs which was verified using platelets and VSMCs transwell co-culture system. Besides, podosome, an invasive protrusion to mediate extracellular matrix (ECM) remodeling, was formed in VSMCs to induce cell migration. Furthermore, MMP-9 activity detected by gelatin zymography was used to verify the function of the podosome in ECM remodeling. The result indicated that MMP-9 activity was robustly activated in VSMCs to implement the function of the podosome. In addition, gelatin degradation was detected in intact VSMCs using a gelatin degradation assay after co-culture with platelets. Taken together, our data reveal a novel mechanism that PMVs promote VSMC migration via forming podosomes and inducing MMP-9 activity.

Anisodamine and anisodine have been used in treatment of septic shock, but the underlying mechanism are still unclear. In the present study, the effects of anisodamine hydrobromide (Ani HBr) and anisodine hydrobromide (AT3) on the mesenteric hemodynamics in septic shock rats were performed. The rat model of septic shock was established by intravenous tail vein injection of 5 ​mg/kg lipopolysaccharide (LPS), and then treated with Ani HBr, AT3, racemic anisodine (Race Ani) or atropine (ATP). The mesenteric microcirculation was observed using the intravital microscopy. Then, the flow pattern of the microcirculation, leukocytes dynamics and the plasma levels of cytokines tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) were analyzed. Compared with the control rats, reduced mean arterial pressure, increased heart rate, and slow microcirculatory blood flow was found in septic shock rats. The main abnormal flow patterns were intermittent and reciprocating motions. Ani HBr, AT3, Race Ani and ATP elevated the mean arterial pressure and reduced heart rate in septic shock rats. Ani HBr and AT3 not only restored the velocity of microcirculatory blood flow and improved the microcirculatory flow patterns, but also suppressed the LPS-induced leukocyte-endothelium interaction and releases of TNF-α and IL-6. Therefore, Ani HBr and AT3 improves hemodynamics in both macro- and microcirculation, which provide a novel experimental basis for exploring the mechanobiological mechanisms in septic shock.