Injectable bioresponsive bone adhesive hydrogels inhibit NLRP3 inflammasome on demand to accelerate diabetic fracture healing.

Diabetes is associated with excessive inflammation, which negatively impacts the fracture healing process and delays bone repair. Previously, growing evidence indicated that activation of the nod-like receptor (NLR) family, such as nod-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome induces a vicious cycle of chronic low-grade inflammatory responses in diabetic fracture. Here, we describe the synthesis of a bone adhesive hydrogel that can be locally injected into the fracture site and releases a natural inhibitor of NLRP3 (rutin) in response to pathological cue reactive oxygen species activity (ROS).

Self-Adaptive Nanocarriers Overcome Multiple Physiological Barriers to Boosting Chemotherapy of Orthotopic Pancreatic Cancer.

Chemotherapy is the primary treatment option for pancreatic cancer, although nanocarrier-based drug delivery systems often struggle with multiple physiological barriers, limiting their therapeutic efficacy. Here, we developed a pH/reactive oxygen species (ROS) dual-sensitive self-adaptive nanocarrier (DAT) encapsulating camptothecin (CPT), an analog of the pancreatic chemotherapeutic drug irinotecan (CPT-11), to enhance chemotherapy outcomes in orthotopic pancreatic cancer by addressing multiple physiological barriers. The nanocarrier features a peripherally positively charged arginine (Arg) residue on DAT and is masked with an acid-labile 2,3-dimethylmaleic anhydride (DA) to improve circulation time.

Strategy and Design of In Situ Activated Protein Hydrolysis Targeted Chimeras.

Protein hydrolysis targeted chimeras (PROTACs) represent a different therapeutic approach, particularly relevant for overcoming challenges associated with traditional small molecule inhibitors. These challenges include targeting difficult proteins that are often deemed "undruggable" and addressing issues of acquired resistance. PROTACs employ the body's own E3 ubiquitin ligases to induce the degradation of specific proteins of interest (POIs) through the ubiquitin-proteasome pathway.

Remodel Heterogeneous Electrical Microenvironment at Nano-Scale Interface Optimizes Osteogenesis by Coupling of Immunomodulation and Angiogenesis.

Immunomodulation is essential for implants to regulate tissue regeneration, while bioelectricity plays a fundamental role in regulating immune activities. Under natural preferences, the bone matrix electrical microenvironment is heterogeneous in the nanoscale, which provides fundamental electrical cues to regulate bone immunity and regenerative repair. However, remodeling bone nanoscale heterogeneous electrical microenvironment remains a challenge, and the underlying immune modulation mechanism remains to be explored.

A Near-Infrared II Luminogen with a Photothermal Effect toward Tumor Drug Resistance Reversal.

Multidrug resistance of tumor cells has greatly limited the chemotherapy effect. The development of reliable strategies to deal with tumor multidrug resistance is highly desirable for tumor therapy. In this work, a near-infrared II (NIR II) luminogen was rationally designed and prepared, which could act as a photothermal reagent to reverse the drug resistance of tumor cells by reducing the related protein expression, achieving a high inhibition efficiency with the synergistic effect of chemotherapeutic drugs.

Matrix Viscoelasticity Controls Differentiation of Human Blood Vessel Organoids into Arterioles and Promotes Neovascularization in Myocardial Infarction.

Stem cell-derived blood vessel organoids are embedded in extracellular matrices to stimulate vessel sprouting. Although vascular organoids in 3D collagen I-Matrigel gels are currently available, they are primarily capillaries composed of endothelial cells (ECs), pericytes, and mesenchymal stem-like cells, which necessitate mature arteriole differentiation for neovascularization. In this context, the hypothesis that matrix viscoelasticity regulates vascular development is investigated in 3D cultures by encapsulating blood vessel organoids within viscoelastic gelatin/β-CD assembly dynamic hydrogels or methacryloyl gelatin non-dynamic hydrogels.

Constructions, Purifications and Applications of DNA-Antibody Conjugates: A Review.

A DNA-antibody conjugate is a synthetic molecule that combines the unique functions of both an antibody and DNA. With the increased accessibility of commercialized kits, the procedure for constructing conjugates is simplified and the requirement for chemistry background is reduced. As a result, the difficulty of preparing a DNA-antibody conjugate has been significantly lowered.

Engineering a Near-Infrared Spiro-Based Aggregation-Induced Emission Luminogen for DNAzyme-Sensitized Photothermal Therapy with High Efficiency and Accuracy.

Aggregation-induced emission luminogen (AIEgens)-based photothermal therapy (PTT) has grown into a sparkling frontier for tumor ablation. However, challenges remain due to the uncoordinated photoluminescence (PL) and photothermal properties of classical AIEgens, along with hyperthermia-induced antiapoptotic responses in tumor cells, hindering satisfactory therapeutic outcomes. Herein, a near-infrared (NIR) spiro-AIEgen was designed for boosted PTT by auxiliary DNAzyme-regulated tumor cell sensitization.

2D Materials-Based Field-Effect Transistor Biosensors for Healthcare.

The need for accurate point-of-care (POC) tools, driven by increasing demands for precise medical diagnostics and monitoring, has accelerated the evolution of biosensor technology. Integrable 2D materials-based field-effect transistor (2D FET) biosensors offer label-free, rapid, and ultrasensitive detection, aligning perfectly with current biosensor trends. Given these advancements, this review focuses on the progress, challenges, and future prospects in the field of 2D FET biosensors.

Controllable multivalent LYTACs enhance targeted protein degradation.

We present a versatile DNA-based LYTAC framework that allows control over the valency of chimeras and the distance between ligands through DNA self-assembly. By evaluating the degradation capabilities of LYTACs with 1, 3, and 9 valences, we confirm the broad applicability of the multivalent enhancement effect across different lysosome-targeting receptor-mediated degradation pathways. Our findings provide valuable insights into improving the degradation efficiency of LYTACs.

Enhancing protective immunity against SARS-CoV-2 with a self-amplifying RNA lipid nanoparticle vaccine.

RNA-based vaccines against SARS-CoV-2 have demonstrated promising protective immunity against the global COVID-19 epidemic. Enhancing the intensity and duration of mRNA antigen expression is anticipated to markedly boost antiviral immune responses. Self-amplifying RNA (saRNA) represents a next-generation platform for RNA-based vaccines, amplifying transcripts in situ to augment the expression of encoded immunogens.

[Analysis on Evaluation Method of Mechanically-Induced Hemolysis of Medical Devices].

Mechanically-induced hemolysis is an important index for evaluating the blood compatibility of medical devices. It mainly evaluates the risk of mechanical hemolysis under simulated clinical use conditions of medical devices. The existing hemolysis test standards mainly evaluate the risk of material-induced hemolysis and cannot evaluate the risk of mechanically-induced hemolysis.

Photocatalytic therapy via photoinduced redox imbalance in biological system.

Redox balance is essential for sustaining normal physiological metabolic activities of life. In this study, we present a photocatalytic system to perturb the balance of NADH/NAD in oxygen-free conditions, achieving photocatalytic therapy to cure anaerobic bacterial infected periodontitis. Under light irradiation, the catalyst TBSMSPy can bind bacterial DNA and initiate the generation of radical species through a multi-step electron transfer process.

Personalizing-TCP porous scaffolds to promote osteogenesis: a study of segmental femoral defects in beagle models.

The increasing clinical occurrence of segmental bone defects is demanding constant improvements in bone transplantation to overcome issues of limited resources, immune rejection and poor structural complement. This study aimed to develop a personalized bone defect repair modality using 3D-printed tricalcium phosphate (-TCP) grafts and to assess its osteogenic impacts in a femoral segmental defect model in beagles, as a basis for clinical studies and application. A-TCP scaffold was designed and manufactured using computer-aided design.

Tumor Site-Specific In Vivo Theranostics Enabled by Microenvironment-Dependent Chemical Transformation and Self-Amplifying Effect.

Precise tumor diagnosis and treatment remain complex challenges. While numerous fluorescent probes have been developed for tumor-specific imaging and therapy, few exhibit effective function in vivo. Herein, a probe called TQ-H is designed that can realize robust theranostic effects both in vitro and in vivo.

Efficacy of pH-Responsive Surface Functionalized Titanium Screws in Treating Implant-associated S. aureus Osteomyelitis with Biofilms Formation.

Implant-associated Staphylococcus aureus (S. aureus) osteomyelitis (IASO) leads to high orthopedic implant failure rates due to the formation of Staphylococcal abscess community within the bone marrow and bacterial colonization in the osteocyte lacuno-canalicular network (OLCN). To address this, antimicrobial peptides (HHC36)-loaded titania nanotubes (NTs) are developed on titanium screws (Ti-NTs-P-A), which integrate pH-responsive polymethacrylic acid to control HHC36 release for eradicating bacteria in IASO.

Calcium Phosphate Loaded with Curcumin Prodrug and Selenium Is Bifunctional in Osteosarcoma Treatments.

Although SeO ions have been loaded onto calcium phosphate to treat a wide range of cancers, the quest to promote bone tissue regeneration is still ongoing. Curcumin (cur), an herbal extraction, can selectively inhibit tumor cells and promote osteogenesis. In this study, SeO ions were co-precipitated in biomimetic calcium phosphate (Se@BioCaP), and modified curcumin prodrug (mcur) was adsorbed on diverse Se@BioCaP surfaces (mcur-Se@BioCaP-Ads).

Subtle Modifications in Interface Configurations of Iron/Cobalt Phthalocyanine-Based Electrocatalysts Determine Molecular CO Reduction Activities.

Strain engineering has emerged as a powerful approach in steering material properties. However, the mechanism and potential limitations remain poorly understood. Here we report that subtle changes in molecular configurations can profoundly affect, conducively or adversely, the catalytic selectivity and product turnover frequencies (TOFs) of CO reduction reaction.

Dentin tubules as a long-term sustained release carrier to accelerate bone repair by loading FTY720.

The controlled release of drugs remains a huge challenge in the field of tissue engineering. Current research focuses on the construction of drug carriers by using various advanced technologies. However, the pore-like structure that exists within our human body is ignored.

Deciphering Design of Aggregation-Induced Emission Materials by Data Interpretation.

This work presents a novel methodology for elucidating the characteristics of aggregation-induced emission (AIE) systems through the application of data science techniques. A new set of chemical fingerprints specifically tailored to the photophysics of AIE systems is developed. The fingerprints are readily interpretable and have demonstrated promising efficacy in addressing influences related to the photophysics of organic light-emitting materials, achieving high accuracy and precision in the regression of emission transition energy (mean absolute error (MAE) ∼ 0.