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The long-dreamed-of capability of monitoring the molecular machinery in living systems has not been realized yet, mainly due to the technical limitations of current sensing technologies. However, recently emerging quantum sensors are showing great promise for molecular detection and imaging. One of such sensing qubits is the nitrogen−vacancy (NV) center, a photoluminescent impurity in a diamond lattice with unique roomtemperature optical and spin properties. This atomic-sized quantum emitter has the ability to quantitatively measure nanoscale electromagnetic fields via optical means at ambient conditions. Moreover, the unlimited photostability of NV centers, combined with the excellent diamond biocompatibility and the possibility of diamond nanoparticles internalization into the living cells, makes NV-based sensors one of the most promising and versatile platforms for various life-science applications. In this review, we will summarize the latest developments of NV-based quantum sensing with a focus on biomedical applications, including measurements of magnetic biomaterials, intracellular temperature, localized physiological species, action potentials, and electronic and nuclear spins. We will also outline the main unresolved challenges and provide future perspectives of many promising aspects of NV-based bio-sensing.

Growth factors and mechanical cues synergistically affect cellular functions, triggering a variety of signaling pathways. The molecular levels of such cooperative interactions are not fully understood. Due to its role in osteogenesis, the growth factor bone morphogenetic protein 2 (BMP‐2) is of tremendous interest for bone regenerative medicine, osteoporosis therapeutics, and beyond. Here, contribution of BMP‐2 signaling and extracellular mechanical cues to the osteogenic commitment of C2C12 cells is investigated. It is revealed that these two distinct pathways are integrated at the transcriptional level to provide multifactorial control of cell differentiation. The activation of osteogenic genes requires the cooperation of BMP‐2 pathway‐associated Smad1/5/8 heteromeric complexes and mechanosensitive YAP/TAZ translocation. It is further demonstrated that the Smad complexes remain bound onto and active on target genes, even after BMP‐2 removal, suggesting that they act as a “molecular memory unit.” Thus, synergistic stimulation with BMP‐2 and mechanical cues drives osteogenic differentiation in a programmable fashion.

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Cells reside in a dynamic microenvironment in which adhesive ligand availability, density, and diffusivity are key factors regulating cellular behavior. Here, the cellular response to integrin‐binding ligand dynamics by directly controlling ligand diffusivity via tunable ligand–surface interactions is investigated. Interestingly, cell spread on the surfaces with fast ligand diffusion is independent of myosin‐based force generation. Fast ligand diffusion enhances α5β1 but not αvβ3 integrin activation and initiates Rac and RhoA but not ROCK signaling, resulting in lamellipodium‐based fast cell spreading. Meanwhile, on surfaces with immobile ligands, αvβ3 and α5β1 integrins synergistically initiate intracellular‐force‐based canonical mechanotransduction pathways to enhance cell adhesion and osteogenic differentiation of stem cells. These results indicate the presence of heretofore‐unrecognized pathways, distinct from canonical actomyosin‐driven mechanisms, that are capable of promoting cell adhesion.

Bone repair in patients with osteoporosis remains a big challenge because their injury sites are often accompanied by an abnormal level of inflammation and reactive oxygen species (ROS). ROS is previously visualized, represented by hydrogen peroxide (H 2 O 2 ), in the bone defects. In this study, the H 2 O 2 in osteoporosis animals is further visualized, and it is found that the expression of H 2 O 2 is markedly higher than that in normal animals. Subsequently, a composite hydrogel containing manganese dioxide (MnO 2 )-coated calcium phosphate microspheres loaded with fibroblast activating protein inhibitor (FAPi) is prepared. Among them, MnO 2 is designed to act as an advanced army to eliminate H 2 O 2 and generate oxygen, and constant release of FAPi is used to regulate the immune response and bone formation. In vitro experiments show that the hydrogels effectively reduce intracellular ROS, guide macrophages toward M2 polarization, and alleviate inflammation. Furthermore, the hydrogels enhance the osteogenesis and inhibit osteoclastogenesis. Animal experiments demonstrate that the hydrogels can eliminate ROS, regulate macrophages, and promote repair of osteoporotic bone defects. Together, the findings from this study imply that the multi-pronged approach holds great promise to promote the repair of osteoporotic bone defects by rescuing the ROS microenvironment and guiding the immune response.

UV‐light‐responsive azobenzene (Azo)/cyclodextrin (CD) host‐guest complexes are attractive for designing smart stimuli‐responsive materials, and have been extensively investigated over the past three decades. However, when applied in biomedical fields, as a result of the harmfulness and poor penetrability of UV light to human tissue, Azo/CD host‐guest complexes responsive to light of longer wavelengths is required. In this Minireview, we reviewed the traditional UV‐light‐responsive Azo/CD host‐guest systems and developments to red‐shift the switching light to the visible or even to the near‐infrared (NIR) light region. “Indirect” methods, including upconversion and two‐photon processes, and “direct” methods to chemically modify Azo molecules for red‐shifting the inducing light were summarized and compared. In addition to biomedical applications, we provide an overview of the potential of visible/NIR‐light‐responsive Azo/CD host–guest complexes in the design of intelligent multifunctional supramolecular materials that function through orthogonal light control.

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