Yongliang Wang

PLGA/HA biomaterials have been widely applied in tissue engineering and regenerative medicine for decades. In bone regeneration, PLGA/HA has been fabricated into films and porous scaffolds and further functionalized with bioactive peptides to enhance angiogenesis and osteogenic differentiation. GFOGER, a collagen-derived motif recognized by integrin α2β1, provides specific adhesion cues that regulate the attachment and osteogenic commitment of bone marrow mesenchymal stromal cells (BMSCs). In this study, we fabricated a PLGA/HA electrospun scaffold and functionalized its surface with GFOGER peptide. The scaffold's surface morphology, chemical composition, wettability, and structural properties were characterized using scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, and contact angle analysis. Cytocompatibility was verified by MTT assay, demonstrating the suitability of the scaffold for cell culture. Importantly, BMSCs cultured on PLGA/HA/GFOGER scaffolds exhibited enhanced osteogenic differentiation, as evidenced by the upregulation of Runx2, BMP2, and OCN. These findings support the potential of PLGA/HA/GFOGER composite scaffolds as promising biomaterials for bone regeneration applications.

Correction for ‘A multiplexed tension sensor reveals the distinct levels of integrin-mediated forces in adherent cells’ by Xiaojun Liu et al., Mater. Adv. , 2024, 5 , 9220–9230, https://doi.org/10.1039/D4MA00600C.

Mechanical stimulation plays a crucial role in numerous biological activities, including tissue development, regeneration and remodeling. Understanding how cells respond to their mechanical microenvironment is vital for investigating mechanotransduction with adequate spatial and temporal resolution. Cell force sensing—also known as mechanosensation or mechanotransduction—involves force transmission through the cytoskeleton and mechanochemical signaling. Insights into cell–extracellular matrix interactions and mechanotransduction are particularly relevant for guiding biomaterial design in tissue engineering. To establish a foundation for mechanical biomedicine, this review will provide a comprehensive overview of cell mechanotransduction mechanisms, including the structural components essential for effective mechanical responses, such as cytoskeletal elements, force-sensitive ion channels, membrane receptors and key signaling pathways. It will also discuss the clutch model in force transmission, the role of mechanotransduction in both physiology and pathological contexts, and biomechanics and biomaterial design. Additionally, we outline analytical approaches for characterizing forces at cellular and subcellular levels, discussing the advantages and limitations of each method to aid researchers in selecting appropriate techniques. Finally, we summarize recent advancements in cell force sensing and identify key challenges for future research. Overall, this review should contribute to biomedical engineering by supporting the design of biomaterials that integrate precise mechanical information.

High-motile fish keratocytes exhibited integrin-mediated forces ranging from 44 to 100 pN, whereas low-motile 3T3L1 and NRK cells generated integrin-mediated forces exceeding 100 pN.

Podosomes and invadopodia, collectively termed invadosomes, are adhesive and degradative membrane structures formed in many types of cells and are well known for recruiting various proteases. However, another major class of degradative enzymes, deoxyribonuclease (DNase), remains unconfirmed and not studied in invadosomes. Here, using surface-immobilized nuclease sensor (SNS), we demonstrated that invadosomes recruit DNase to their core regions, which degrade extracellular double-stranded DNA. We further identified the DNase as GPI-anchored membrane-bound DNase X. DNase recruitment is ubiquitous and consistent in invadosomes of all tested cell types. DNase activity exhibits within a minute after actin nucleation, functioning concomitantly with protease in podosomes but preceding it in invadopodia. We further showed that macrophages form DNase-active podosome rosettes surrounding bacteria or micropatterned antigen islets, and the podosomes directly degrade bacterial DNA on a surface, exhibiting an apparent immunological function. Overall, this work reports DNase in invadosomes for the first time, suggesting a richer arsenal of degradative enzymes in invadosomes than known before.

Yellow fluorescent protein serves as a label-free tension sensor to monitor integrin tension.

A rigid chiral acyclic chelator H₂CHXhox was synthesized and evaluated for Ga³⁺-based radiopharmaceutical applications; it was compared to the previously reported hexadentate H₂hox to determine the effect of a backbone reinforced from adding a chiral 1S,2S-trans-cyclohexane on metal complex stability, kinetic inertness, and in vivo pharmacokinetics. NMR spectroscopy and theoretical calculation revealed that [Ga(CHXhox)]⁺ showed a very similar coordination geometry to that of [Ga(hox)]⁺, and only one isomer in solution was observed by NMR spectroscopy. Solution studies showed that the modification results in a significant improvement in the exceptionally high thermodynamic stability of [Ga(hox)]⁺ with a 1.56 log unit increase in stability constant (logK_ML = 35.91(1)). More importantly, H₂CHXhox showed very fast Ga³⁺ complexation at physiological pH 7.4, and acid-assisted Ga³⁺ complex dissociation kinetic studies (pH 1) in comparison with H₂hox revealed a 50-fold increase of the dissociation half-life time from 73 min to 58 h. Fluorescence microscopy imaging study confirmed its cellular uptake and accumulation in endoplasmic reticulum and mitochondria. MTT studies indicated a quite low cytotoxicity of [Ga(CHXhox)]⁺ over a large concentration range. Dynamic PET imaging studies showed no accumulation in muscle, lungs, bone, and brain, suggesting no release of free Ga³⁺ ions. [⁶⁸Ga][Ga(CHXhox)]⁺ is cleared from the mouse via hepatobiliary and renal pathways. Compared to [⁶⁸Ga][Ga(hox)]⁺, the increased lipophilicity of [⁶⁸Ga][Ga(CHXhox)]⁺ enhanced heart and liver uptake and decreased kidney clearance. [⁶⁷Ga][Ga(CHXhox)]⁺ SPECT/CT imaging and biodistribution study revealed good clearance from liver to gallbladder after 90 min and finally into feces after 5 h. No decomposition or transchelation was observed over the 5 h study. These results confirmed H₂CHXhox to be an obvious improvement over H₂hox and an excellent candidate in this new “ox” family for the development of radiopharmaceutical compounds.

Nucleases are important enzymes that cleave nucleic acids and play critical roles in DNA repair, immune defense and potentially in cancer invasion. However, their spatial dynamics at subcellular level is much less studied. Here, we developed a surface‐tethered nuclease sensor (SNS) which directly converts membrane‐bound nuclease (MN) activity to fluorescent signal, therefore, mapping MN activity on cell adhesion sites with high resolution and sensitivity. With SNS, we studied MN activity on the ventral membrane of cancer cells, where MN activity initially occurs in punctate regions and advances in a coral‐shaped pattern. In six tested cell‐lines, the MN activity levels in cancer cells are significantly higher than those in non‐cancer cells. We then tested SNS as a sensitive approach to detect cancer cells at single cell level. Single breast cancer cells were successfully detected from thousands of adherent non‐cancer cells and from millions of non‐adherent blood cells.