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Bone injuries and diseases are associated with profound changes in the biophysical properties of living bone tissues, particularly their electrical and mechanical properties. The biophysical properties of healthy bone are attributed to the complex network of interactions between its various cell types (i.e., osteocytes, osteoclast, immune cells and vascular endothelial cells) with the surrounding extracellular matrix (ECM) against the backdrop of a myriad of biomechanical and bioelectrical stimuli arising from daily physical activities. Understanding the pathophysiological changes in bone biophysical properties is critical to developing new therapeutic strategies and novel scaffold biomaterials for orthopedic surgery and tissue engineering, as well as provides a basis for the application of various biophysical stimuli as therapeutic agents to restore the physiological microenvironment of injured/diseased bone tissue, to facilitate its repair and regeneration. These include mechanical, electrical, magnetic, thermal and ultrasound stimuli, which will be critically examined in this review. A significant advantage of utilizing such biophysical stimuli to facilitate bone healing is that these may be applied non-invasively with minimal damage to surrounding tissues, unlike conventional orthopedic surgical procedures. Furthermore, the effects of such biophysical stimuli can be localized specifically at the bone defect site, unlike drugs or growth factors that tend to diffuse away after delivery, which may result in detrimental side effects at ectopic sites.

Background: Little is known about the associations of changes in drinking levels with the newly defined metabolic dysfunction-associated steatotic liver disease (MASLD). We therefore sought to estimate the associations between changes in drinking levels and MASLD in less developed regions of China. Methods: This longitudinal study included 8727 participants from the China Multi-Ethnic Cohort (CMEC) in less developed regions, all participating in baseline and a follow-up survey. MASLD was defined as hepatic steatosis, along with the presence of at least one of five cardiometabolic risks, in addition to limiting excessive alcohol consumption. We applied the parametric g-formula to evaluate the association between changes in drinking levels and MASLD. We further estimated the association between changes in drinking levels and fibrosis scores (AST-to-platelet ratio and fibrosis-4 index) in patients with MASLD. Results: Compared with sustained non-drinking, sustained modest drinking was associated with a higher risk of MASLD (Mean Ratio (MR): 1.127 [95% CI: 1.040–1.242]). Compared to sustained non-drinking, the MR for those transitioning from non-drinking to modest drinking was 1.065 [95% CI: 0.983–1.169], while the MR for those changing from modest drinking to non-drinking was 1.059 [95% CI: 0.965, 1.173]. Non-invasive fibrosis scores tended to increase with modest drinking compared to sustained non-drinking. Conclusion: In the less developed regions of China, sustained moderate drinking was associated with the risk of MASLD compared with sustained non-drinking. Increased drinking showed a trend towards a higher risk of MASLD. This study can inform drinking policies related to MASLD and liver fibrosis in less developed regions. [ABSTRACT FROM AUTHOR]

Biophysical cues play a crucial role in T cell biology, yet their implications in adoptive T cell therapy (ACT) remain largely unknown. Here, we investigate the effect of electrical stimuli on CD8+ T cells using a charged substrate composed of electroactive nanocomposites with tunable surface charge intensities. Electrical stimuli enhance the persistence and tumor-suppressive efficacy of transferred T cells, with effects dependent on substrate charge. Single-cell RNA-sequencing analysis unveils a decrease in virtual memory T (Tvm) cells and an increase in proliferative potential T (Tpp) cells, which exhibit superior antitumor activity and metabolic adaptations relative to those treated with uncharged substrate. ATAC-seq profiling demonstrates heightened accessibility at upstream binding sites for EGR1, a transcription factor critical for Tpp cell differentiation. Mechanistically, the charged substrate disrupts ionic TCR-lipid interactions, amplifies TCR signaling, and activates EGR1, thereby impeding Tvm polarization during ex vivo culture. Our findings thus highlight the importance of extracellular electrical stimuli in shaping T cell fate, offering potential for optimizing ACT for therapeutic applications. Biophysical cues play a crucial role in T cell biology, yet their implications in adoptive T cell therapy remain elusive. Here the authors use a charged substrate to enhance T cell proliferation and anti-tumor function for adoptive transfer therapy, with the mechanism of amplifying TCR signaling, activating EGR1 signaling and impeding virtual memory T polarization. [ABSTRACT FROM AUTHOR]

A new synthetic route to 2-sulfonylbenzothiazoles (BtsR) employing cascade SO2−–NCS nucleophilic addition and CuI-catalysed S–C(sp2) coupling was developed. Structurally diverse BtsR molecules were readily afforded in high yields from the rapid and benign reaction of 2-iodoarylisothiocyanates with sodium sulfinates in DMSO, generally without the need for further column isolation. [ABSTRACT FROM AUTHOR]

Regulation of the immune response is key to promoting bone regeneration by electroactive biomaterials. However, how electrical signals at the micro- and nanoscale regulate the immune response and subsequent angiogenesis during bone regeneration remains to be elucidated. Here, the distinctly different surface potential distributions on charged poly(vinylidene fluoridetrifluoroethylene) (P(VDF-TrFE)) matrix surfaces are established by altering the dimensions of ferroelectric nanofillers from 0D BaTiO 3 nanoparticles (homogeneous surface potential distribution, HOPD) to 1D BaTiO 3 nanofibers (heterogeneous surface potential distribution, HEPD). Compared to HOPD, HEPD is significantly better at inducing the M2 polarization of macrophages and promoting neovascularization, which results in accelerated bone regeneration in vivo. The transcriptomic analysis reveals that macrophages modulated by HEPD display high expression levels of pro-angiogenic genes, which is corroborated by tube-formation assays, RT-qPCR, and western blot analyses in vitro. Mechanistic explorations elucidate activation of the PI3K-Akt signaling pathway, which in turn induces the polarization of macrophages toward a pro-angiogenic phenotype. This study elucidates the cascade of biological processes by which heterogeneous electrical signals at the micro- and nanoscale modulate macrophage functions to promote vascularization and bone regeneration. Hence, this study provides new insights into how the micro- and nanoscale distribution characteristics of electrical signals facilitate bone regeneration., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The electrical properties of bone implant scaffolds are a pivotal factor in regulating cellular behavior and promoting osteogenesis. The previous study shows that built-in electric fields established between electropositive nanofilms and electronegative bone defect walls are beneficial for promoting bone defect healing. Considering that the physiological electrical microenvironment is spatially distributed in 3D, it is imperative to establish a 3D spatial charged microenvironment on bone scaffolds to optimize the efficacy of osseointegration. Nevertheless, this still poses a formidable challenge. Here, a bone repair strategy that utilizes micro-scale 3D topography is developed on a piezoelectric BaTiO 3 (BTO) substrate to provide 3D spatial electrical stimulation. The BTO micropillar arrays, especially with a height of 50 µm and positive-charge distribution (50 µm positive), promote the spreading, cytoskeletal reorganization, focal adhesion maturation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). They enhanced the clustering of mechanosensing integrin α5 in BMSCs. The biomimetic 3D spatial electrical microenvironment accelerated bone repair and osseointegration in a rat femoral diaphysis defect repair model. The study thus reveals that implants with a 3D spatial electrical microenvironment can significantly enhance osseointegration, thereby providing a new strategy to optimize the performance of electroactive biomaterials for tissue regenerative therapies., (© 2024 Wiley‐VCH GmbH.)