Up IGF-I via high-toughness adaptive hydrogels for remodeling growth plate of children.

The growth plate is crucial for skeletal growth in children, but research on repairing growth plate damage and restoring growth is limited. Here, a high-toughness adaptive dual-crosslinked hydrogel is designed to mimic the growth plate's structure, supporting regeneration and bone growth. Composed of aldehyde-modified bacterial cellulose (DBNC), methacrylated gelatin (GelMA) and sodium alginate (Alg), the hydrogel is engineered through ionic bonding and Schiff base reactions, creating a macroporous structure.

Irreversible electroporation combined with PD-L1/IL-6 dual blockade promotes anti-tumor immunity via cDC2/CD4T cell axis in MHC-I deficient pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a "cold" solid tumor with frequent Major Histocompatibility Complex I (MHC-I) deficiency, thereby making it resistant to type-1-conventional dendritic cell (cDC1)-CD8T cell mediated anti-tumor immunity. Current studies have demonstrated the emerging compensatory role of MHC-II-mediated antigen presentation and CD4T cell activation in anti-tumor immunity against MHC-I-deficient tumors. However, the underlying mechanism of the compensatory immune response by CD4T cells in cancer ablation therapy remains to be elucidate.

β-Diketone Functionalized Microspheres Chelate Reactive Iron via Metal Coordination for Cartilage Repair.

Excessive intracellular iron accumulation can induce mitochondrial dysfunction, leading to chondrocyte ferroptosis, a key contributor to cartilage damage in osteoarthritis (OA). Here, micelle-microfluidic hydrogel microspheres, featuring keto-enol-thiol bridged nano-sized secondary structures that disintegrate within the intracellular peroxidative environment to reveal β-diketone groups with metal chelation capabilities, are utilized for the in situ removal of reactive iron, thereby facilitating cartilage repair through the restoration of mitochondrial homeostasis. The relevant experiments demonstrate that the microspheres reduce iron influx by downregulating transferrin receptor (TfR1) expression and decrease mitochondrial iron uptake by upregulating mitochondrial outer membrane iron-sulfur cluster protein (CISD1), thus restoring intracellular mitochondrial iron homeostasis.

Cerium Dioxide Nanoparticles-Based Inspector Enhances Mitochondrial Quality Control to Maintain Chondrocyte Homeostasis in Osteoarthritis Therapy.

Imbalanced mitochondrial quality control is strongly linked to the onset and development of osteoarthritis (OA). However, current research primarily focuses on local cartilage repair and phenotype maintenance, lacking a systematic approach to subcellular mitochondrial quality control. To address this, the present study proposes a mitochondrial quality control strategy based on nanozyme hydrogel microspheres ("mitochondrial inspector"), constructed through electrostatic self-assembly, incorporation of dynamic diselenide bonds, and microfluidic technology.

Biosynthesis of Lysosomally Escaped Apoptotic Bodies Inhibits Inflammasome Synthesis in Macrophages.

Hyperglycemia and bacterial colonization in diabetic wounds aberrantly activate Nod-like receptor protein 3 (NLRP3) in macrophages, resulting in extensive inflammatory infiltration and impaired wound healing. Targeted suppression of the NLRP3 inflammasome shows promise in reducing macrophage inflammatory disruptions. However, challenges such as drug off-target effects and degradation via lysosomal capture remain during treatment.

Reduce electrical overload via threaded Chinese acupuncture in nerve electrical therapy.

Bioelectrical stimulation is a powerful technique used to promote tissue regeneration, but it can be hindered by an "electrical overload" phenomenon in the core region of stimulation. We develop a threaded microneedle electrode system that protects against "electrical overload" by delivering medicinal hydrogel microspheres into the core regions. The threaded needle body is coated with polydopamine and chitosan to enhance the adhesion of microspheres, which are loaded into the threaded grooves, allowing for their stereoscopic release in the core regions.

In Situ Proefferocytosis Microspheres as Macrophage Polarity Converters Accelerate Osteoarthritis Treatment.

Efferocytosis in macrophages typically engages an anti-inflammatory positive feedback regulatory mechanism. In osteoarthritis (OA), characterized by imbalanced inflammatory homeostasis, the proinflammatory state of macrophages in the immune microenvironment can be reversed through enhanced efferocytosis. This study develops an in situ proefferocytosis hydrogel microsphere (macrophage polarity converter, H-C@IL) for OA treatment.

Drug-phospholipid conjugate nano-assembly for drug delivery.

Phospholipid-based liposomes are among the most successful nanodrug delivery systems in clinical use. However, these conventional liposomes present significant challenges including low drug-loading capacity and issues with drug leakage. Drug-phospholipid conjugates (DPCs) and their assemblies offer a promising strategy for addressing these limitations.

Downregulation of the PI3K/AKT/mTOR/MMP-13 pathway for promoting interface healing via lubricating microspheres.

Interface friction impedes tissue healing and stimulates interface cells to produce matrix metalloproteinases (MMPs); however, the precise mechanisms underlying matrix degradation, and the formation of fibrous scars remain unclear. This research involved the development of interface lubricating microspheres that inhibit the PI3K/AKT/mTOR signaling pathway in tenocytes. This inhibition significantly decreased MMP-13 expression and increased COL-1 production, thereby facilitating interface repair and regeneration.

Slide-Ring Structured Stress-Electric Coupling Hydrogel Microspheres for Low-Loss Transduction Between Tissues.

High transductive loss at tissue injury sites impedes repair. The high dissipation characteristics in the electromechanical conversion of piezoelectric biomaterials pose a challenge. Therefore, supramolecular engineering and microfluidic technology is utilized to introduce slide-ring polyrotaxane and conductive polypyrrole to construct stress-electric coupling hydrogel microspheres.

Reactive oxygen species switcher via MnO-coated Prussian blue loaded hyaluronic acid methacrylate hydrogel microspheres for local anti-tumor treatment.

ROS-induced therapy can eradicate breast tumors when combined with thermal ablation, but excessive ROS also threatens peritumoral tissue with inflammation. To eradicate tumors and avoid inflammatory sequela, it is necessary to generate ROS in treatment stage and scavenge ROS in prognostic stage. However, it is a great challenge to reverse ROS in different stages.

Intelligent Hydrogel-Assisted Hepatocellular Carcinoma Therapy.

Given the high malignancy of liver cancer and the liver's unique role in immune and metabolic regulation, current treatments have limited efficacy, resulting in a poor prognosis. Hydrogels, soft 3-dimensional network materials comprising numerous hydrophilic monomers, have considerable potential as intelligent drug delivery systems for liver cancer treatment. The advantages of hydrogels include their versatile delivery modalities, precision targeting, intelligent stimulus response, controlled drug release, high drug loading capacity, excellent slow-release capabilities, and substantial potential as carriers of bioactive molecules.

Local glycolysis-modulating hydrogel microspheres for a combined anti-tumor and anti-metastasis strategy through metabolic trapping strategy.

Anti-glycolysis is well-recognized for inhibition of tumor proliferation. However, tumor metabolic heterogeneity confers great challenges in the therapeutic efficacy of glycolysis inhibitors. Here, a metabolic trapping strategy was employed to avoid metabolism heterogeneity in tumors.

Precise Cell Type Electrical Stimulation Therapy Via Force-electric Hydrogel Microspheres for Cartilage Healing.

Electrical stimulation enhances cellular activity, promoting tissue regeneration and repair. However, specific cells and maintaining a stable energy supply are challenges for precise cell electrical stimulation therapy. Here, force-electric conversion hydrogel microspheres (Piezo@CR MPs) is devloped to induce specific stem cell aggregation and promote chondrogenic differentiation through localized electrical stimulation.

Implantable Multifunctional Micro-Oxygen Reservoir System for Promoting Vascular-Osteogenesis via Remodeling Regenerative Microenvironment.

Hypoxia and reactive oxygen species (ROS) overaccumulation cause persistent oxidative stress and impair intrinsic regenerative potential upon tissue injury. For local tissue injury with hypoxia, such as bone fracture and defects, a localized-sufficient oxygen supply is highly desirable but remains challenging. Therefore, to explore a strategy and its intrinsic mechanism for supplying oxygen locally and remodeling the regenerative microenvironment, an innovative oxygenating hydrogel microsphere system with sustained oxygenation and antioxidant properties is introduced by loading CaO@SiO@PDA (CSP) nanoparticles.

Engineered Biomimetic Cancer Cell Membrane Nanosystems Trigger Gas-Immunometabolic Therapy for Spinal-Metastasized Tumors.

Despite great progress in enhancing tumor immunogenicity, conventional gas therapy cannot effectively reverse the tumor immunosuppressive microenvironment (TIME), limiting immunotherapy. The development of therapeutic gases that are tumor microenvironment responsive and efficiently reverse the TIME for precisely targeted tumor gas-immunometabolic therapy remains a great challenge. In this study, a novel cancer cell membrane-encapsulated pH-responsive nitric oxide (NO)-releasing biomimetic nanosystem (MP@AL) is prepared.

Boosting mRNA-Engineered Monocytes via Prodrug-Like Microspheres for Bone Microenvironment Multi-Phase Remodeling.

Monocytes, as progenitors of macrophages and osteoclasts, play critical roles in various stages of bone repair, necessitating phase-specific regulatory mechanisms. Here, icariin (ICA) prodrug-like microspheres (ICA@GM) are developed, as lipid nanoparticle (LNP) transfection boosters, to construct mRNA-engineered monocytes for remodeling the bone microenvironment across multiple stages, including the acute inflammatory and repair phases. Initially, ICA@GM is prepared from ICA-conjugated gelatin methacryloyl via a microfluidics system.

Engineering strategies for apoptotic bodies.

Extracellular vesicles (EVs) are lipid bilayer vesicles containing proteins, lipids, nucleic acids, and metabolites secreted by cells under various physiological and pathological conditions that mediate intercellular communication. The main types of EVs include exosomes, microvesicles, and apoptotic bodies (ABs). ABs are vesicles released during the terminal stages of cellular apoptosis, enriched with diverse biological entities and characterized by distinct morphological features.