Polyphosphate (PolyP) is an inorganic polymer composed of orthophosphate units linked by high-energy phosphate anhydride bonds, widely found in various organisms from bacteria to mammals. In recent years, PolyP has attracted widespread attention in the field of bone tissue engineering due to its unique biological characteristics, possessing both osteoinductive activity and metabolic energy supply functions. This article systematically reviews the molecular structure, physicochemical properties, and multiple mechanisms by which PolyP promotes osteogenic differentiation, as well as biomaterial design strategies based on PolyP. PolyP can synergistically promote osteogenic differentiation through multiple mechanisms, including by acting as a phosphate donor, providing metabolic energy, regulating signaling pathways such as Wnt/β-catenin, and modulating the osteoprotegerin/receptor activator of nuclear factor κB ligand (OPG/RANKL) balance. In terms of material design, PolyP can form nano/microparticles with metal ions such as Ca2+, Sr2+, and Mg2+ and can also be compounded with polymers to construct various forms such as hydrogels, bone cement, and three-dimensional (3D)-printed scaffolds. Preclinical studies have shown that PolyP-incorporated materials exhibit excellent osteogenic performance and biocompatibility in bone defect repair, and preliminary clinical studies have also confirmed its feasibility. This article aims to provide a comprehensive overview of the current applications of PolyP-incorporated materials and delineate future directions, challenges, and necessary pathways for their clinical translation.

Conventional LiFePO4 (LFP) cathodes employing poly(vinylidene fluoride) (PVDF) as binder exhibit relatively stable cycling performance but suffer from poor ionic conductivity, limited rate capability, restricted cycling stability at high current densities, as well as environmental concerns about the high fluorine content of PVDF. Here, we introduce an anion-cluster-mediated Li+ hopping mechanism in a series of newly synthesized and multifunctional poly(ionic liquid) (PIL) binders that can enable high-rate performance with an accelerated Li+ transport by 140-200%, meanwhile reducing the fluorine content by 60%. The counteranion aggregation along the PIL backbones can attract and promote the Li+ migration based on comprehensive validation of nuclear magnetic resonance spectroscopy, cyclic voltammetry and molecular dynamics simulations. The optimized LFP-PIL cathodes deliver superior high-rate performance (a capacity of 100 mAh·g-1 at 15C) and cycling stability (95.5% capacity retention after 500 cycles at 5C). Furthermore, by integrating the chemistry-informed machine learning with experimental validation, we establish a molecular structure design methodology for next-generation PIL binders. This work provides both mechanistic insight and a generalizable design framework for high-performance and sustainable lithium cathode materials.

Maxillofacial electromyographic (EMG) signals serve as crucial indirect indicators of occlusal function, playing a significant role in clinical oral diagnosis. However, conventional gel electrodes with occlusive nature induce skin irritation and wearer discomfort, which limits long-term monitoring. Here, we developed an ultrathin, gas-permeable, and flexible electronic skin (e-skin) designed for imperceptible, long-term maxillofacial EMG monitoring. This e-skin comprises a stretchable substrate formed by core-shell elastic fibers fabricated via coaxial electrospinning, coated with PEDOT:PSS@MXene nanocomposite layers. The cross-linking effect between PEDOT:PSS and MXene (specifically, the hydrogen bonding between MXene and PSS chains and the electrostatic interaction between MXene and PEDOT chains) reduces the interlayer spacing, concurrently delaying MXene oxidation by repelling water and air and enhancing electron transfer between MXene layers. In sEMG measurement trials, the e-skin successfully acquired clear, stable myoelectric signals corresponding to various chewing intensities and patterns (e.g., gum chewing and intermittent occlusion). In particular, ultrathin dimensionality substantially diminishes foreign body perceptibility and associated wearer discomfort, thereby elevating sustained comfort thresholds and long-term therapeutic viability. This work presents a novel material-device strategy for next-generation wearable bioelectric sensing platforms, enabling comfortable, precise monitoring with applications in facial muscle assessment, rehabilitation medicine, and neuromuscular diagnostics.

Despite advances in surgical techniques, functional recovery after peripheral nerve injury remains suboptimal. Peripheral nerve repair requires grafts that concurrently modulate the inflammatory microenvironment and restore bioenergetics, a synergy requirement that has been largely overlooked in previous biomaterial design. To bridge this gap, we developed a polyphosphate (PolyP)-based nerve regenerative platform. This work develops a nerve regenerative hydrogel (PPB) through electrostatic complexation between quaternary ammonium chitosan and bioenergy-active inorganic polymer PolyP, with a natural flavonoid baicalin further stabilizing the network via weak interactions. It endows the composite with injectability, self‑healing, tissue adhesion, and sustained release properties. The constituents of PPB cooperatively elevate intracellular ATP levels, preserve mitochondrial ultrastructure and functions under oxidative and inflammatory stress, promotes Schwann cell and pheochromocytoma 12 proliferation and migration while attenuating inflammatory/oxidative responses. A Swiss-roll-like nerve conduit is manufactured to repair the rat sciatic nerve defects. The implantation realizes an effective recovery of the sciatic nerve functions. Histology confirmed dense myelinated fiber regeneration with mature ultrastructure and successful reinnervation. Both in vitro and in vivo analysis confirms that PPB acts via activating the PI3K/AKT/mTOR signaling pathway. This work establishes a coordinated “energy-immunity” regulation strategy, advancing peripheral nerve regeneration through synchronized bioenergetic activation and microenvironment remodeling.

Infected burn wounds remain a formidable clinical challenge due to persistent oxidative stress, bacterial infection, and dysregulated inflammation. Herein, a multifunctional microneedle (MN) patch is engineered through the in situ integration of gallic acid-iron coordination networks (GFe) onto silk fibroin microspheres (SFMSs). The resulting GFe@SFMSs are encapsulated into a dissolvable MN array, enabling direct intradermal delivery and sequential therapeutic release. Leveraging the relatively weak nature of the coordination bonds, this composite structure exhibits photothermal antibacterial activity (>99% inhibition against E. coli and S. aureus) during the early stage of wound healing, and then gradually degrades in the subsequent phase to release iron ions and gallic acid, conferring durable antioxidant, anti-inflammatory, and chemodynamic effects. Simultaneously, the progressive degradation of SFMSs can activate endogenous regenerative pathways, thereby promoting collagen synthesis and angiogenesis. In a murine infected burn model, the MN patch significantly accelerates wound closure, reduces pro-inflammatory cytokines (TNF-α, IL-6), and enhances tissue remodeling. This work presents a synergistic and spatiotemporally programmable strategy for infected burn healing through the combination of photothermal, chemodynamic, antioxidant, and regenerative functions.

Capping materials are critical for vital pulp therapy in endodontic treatment, whereas the currently available ones remain inadequate in meeting the multiple requirements of the complex tissue defects. Herein, we report an injectable and self-setting calcium polyphosphate coacervate composite (polyP-Ca-CS) that exploits an acid neutralization mechanism based on the coacervate and chitosan, engineered for direct pulp capping. The material leverages polyP-Ca coacervate (formed through liquid-liquid phase separation) as an injectable matrix and chitosan that initiates setting via acid neutralization, enhances mechanical strength, and confers antibacterial properties. polyP-Ca-CS sets into a rigid solid under both aqueous and anhydrous conditions without significant exothermic reaction or volume change-features that are critical for clinical reliability. Mechanistic investigations reveal that neutralization of the coacervate's intrinsic acidity drives the setting, thereby advancing fundamental understanding of setting mechanisms in polyphosphate-based materials. In vitro, polyP-Ca-CS significantly boosts ATP production, mitochondrial function, cell migration, metabolic activity and odontogenic differentiation of dental pulp stem cells (DPSCs). In a rabbit pulp exposure model, it effectively induces reparative dentin formation and preserves pulp vitality, performing comparably to commercial bioceramics. This work presents a bioenergetic-active biomaterial that meets the complex requirements of vital pulp therapy and offers a promising alternative for regenerative endodontics. STATEMENT OF SIGNIFICANCE: This work presents an application of a polyphosphate-based coacervate system in vital pulp therapy, opening an avenue for bioactive dental biomaterials. Besides, it elucidates that setting of the calcium polyphosphate coacervate is driven by acid neutralization, advancing fundamental insights into inorganic coacervate chemistry. The prepared calcium polyphosphate coacervate composite not only meets stringent physical requirements but also activates cellular energy metabolism. Additionally, this work also demonstrates that chitosan-a normal biopolymer-can serve as an setting initiator for inorganic coacervate systems, while simultaneously enhancing mechanical integrity and conferring antibacterial activity.

Peripheral nerve injury triggers slow axonal regeneration and irreversible muscle atrophy due to the absence of synchronous neuromuscular repair strategies. We present a fully implantable, self-powered Mechano-driven Electro-adaptable Bioelectronic Implant System (MEBIS) enabling coordinated mechanical-electrical stimulation for integrated neuromuscular regeneration. A programmable robotic actuator delivers quantifiable mechanical massage to denervated muscle, enhancing perfusion while deforming a nanogenerator that converts motion into localized electrical cues. These signals stimulate injured nerves, inducing intracellular Ca2+ elevation and Ca2+-dependent signaling, which activates downstream HIF-1α/AMPK pathways to accelerate Schwann cell activity, angiogenesis, and axonal regrowth. This mechano-electro-biochemical cascade couples muscle preservation with nerve regeneration in a closed loop, overcoming depth limitations and output instability of conventional stimulators. Validated in rat and porcine models, MEBIS significantly improves functional recovery, electrophysiology, and histomorphometry without biocompatibility concerns. Our platform establishes a scalable, feedback-controlled paradigm for precision repair and rehabilitation after peripheral nerve injury.

Magnetic hydrogels are emerging as intelligent biomaterials that integrate superparamagnetic nanoparticles into hydrogel networks. Under external magnetic fields, they enable remotely controlled targeted delivery, mechanical stimulation, and thermal regulation, offering a strategy for treating bone diseases. This review outlines the construction of magnetic hydrogels and their regulatory mechanisms. At the cellular level, magnetic hydrogels have been associated with several study–specific signaling responses that regulate osteogenic differentiation, macrophage polarization, stem–cell fate, and chondrocyte metabolism. The strength of evidence supporting these mechanisms varies: some pathways are supported by pathway specific molecular assays or pharmacological perturbation, whereas others remain mechanistic hypotheses inferred from established biological knowledge. Simultaneously, these hydrogels guide the differentiation of mesenchymal stem cells and chondrocytes by adjusting the physicochemical microenvironment. In disease models, magnetic hydrogels show integrated therapeutic potential across osteoarthritis, osteosarcoma, fractures, and bone defects, including inflammation modulation, combination tumor therapy, sequential drug release, and defect repair. We further discuss the remaining challenges for clinical translation, including long–term biosafety, magnetic field standardization, manufacturing reproducibility, and structure–property–performance relationships.

Ammonia (NH3) is a toxic and corrosive gas that requires reliable detection at low concentrations for industrial safety, environmental monitoring and indoor air-quality control. Chemiresistive sensors often suffer from a trade-off in which stronger adsorption improves sensitivity but slows recovery and weakens reversibility. To address this issue, interfacial charge transfer was modulated in imidazolium-based ionic porous organic polymers with π-conjugated backbones in both powder and flexible film forms. Ionic-site regulation and polyiodide confinement were applied to powders, and Au decoration was introduced in films to improve interfacial charge transport. Polyiodide-treated I2-PAmTB showed the best powder performance, with a response value of around 35 toward 100 ppm NH3 at 50 °C with strong selectivity and stability. The PAmTB framework was further converted into a flexible device via catalyst-free in situ growth on ITO-PET followed by Au decoration. The resulting Au-PAmTB film enabled heater-free room-temperature NH3 sensing from 2 to 100 ppm with near-linear calibration and a detection limit of 0.14 ppm. It also showed negligible resistance change under repeated bending. These results provide an interfacial-engineering framework that connects ionic-site regulation with charge-transport control, enabling low-power NH3 sensing in both powder and flexible thin-film devices.

Infected diabetic wounds are sustained by a vicious cycle of hyperglycemia-driven bacterial infection, persistent oxidative stress, and excessive inflammation, which collectively disrupt the ordered progression of tissue repair. Here, we engineered a stage-adaptive Janus microneedle patch (MN-FeSAC-PPE) to enable a staged therapeutic process from early antibacterial intervention to subsequent redox-immune microenvironment remodeling and regenerative tissue repair. This stage-adaptive design integrates Fe single-atom nanozymes (Fe-SACs) into the microneedle base to rapidly kill bacteria using near-infrared light, which activates reactive oxygen species (ROS) production, enabling rapid antibacterial activity against wound pathogens. Meanwhile, propolis extract-loaded (PPE) tips deliver antioxidant bioactive compounds into the wound bed to mitigate oxidative stress, modulate the redox-immune microenvironment, and support the inflammatory-to-regenerative transition. In vitro, MN-FeSAC-PPE enhanced antioxidant defense, suppressed pro-inflammatory factors, and protected fibroblasts from oxidative stress-induced mitochondrial dysfunction. Transcriptomic analysis further supported reduced inflammatory signaling and enhanced metabolism-related programs. In S. aureus-infected diabetic wounds, NIR-activated MN-FeSAC-PPE accelerated wound closure, promoted angiogenesis and collagen remodeling, and alleviated inflammation. These findings establish a stageadaptive redox-immune and bioenergetic regulatory microneedle platform for infected diabetic wound repair.

Although traditional cancer therapy is widely used, it still faces treatment and some serious adverse reactions. This study developed an “all-in-one” multifunctional nanotherapeutic agent that integrates the dual capabilities of magnetic resonance imaging (MRI) and photothermal/chemodynamic therapy (PPT/CDT). In brief, a multifunctional nanotherapeutic agent was successfully synthesized for MRI and photothermal/chemodynamic therapy by modifying a manganese gallate complex with dopamine (Mn-GA@PDA NPs). We found that at a concentration of 400 μg/mL of Mn-GA@PDA NPs and under irradiation with near-infrared light at 1.5 W/cm2 for 10 min, the temperature could rapidly rise to 59 ℃. Moreover, the cell survival rate was much lower than that of the group without laser irradiation. In the animal experiment, a significant difference between the Mn-GA@PDA NPs + NIR group and the PBS group. The antitumor effect was 9.5 times that of the PBS group. The in vitro and in vivo experiments demonstrated that the Mn-GA@PDA NPs, possessing chemodynamic and photothermal activity, inhibited the growth of breast cancer 4T1 cells. Due to the inherent high paramagnetism of manganese ion, the Mn-GA@PDA NPs effectively accelerate the longitudinal relaxation rate under normal physiological conditions, demonstrating certain T1-weighted magnetic resonance imaging ability. The calculated molar longitudinal relaxation rate was r1 = 4.4 mM−1 s−1, providing robust support for precision medicine. Our Mn-chelating nanoplatform is a promising MRI–visible theragnostic agent for synergistic cancer combination therapy.

Infected skin defects persist in a pathological state characterized by dysregulation of the immune microenvironment and impaired bioenergetics, requiring coordinated treatment strategies to remold them. Currently developing therapies with coordinated effects are often hampered by incomplete targets, high complexity, and limited clinical performance, underscoring the need for minimalist yet effective strategies that integrate both targets. Here, we address this challenge by designing a two-component system, the polyphosphate-gallic acid (polyP-GA) complex, with high biocompatibility and adaptability to different material forms (e.g., solution, spray, hydrogel, and paste). Based on the mutually complementary and enhanced effects of the two constituents, the polyP-GA complex markedly inhibits bacterial infection, reduces reactive oxygen species (ROS) accumulation, and suppresses inflammation evidenced by facilitated macrophage polarization toward the reparative M2 phenotype and broad related anti-inflammatory transcriptional effects. Concurrently, the polyP-GA complex restores mitochondrial function and elevates intracellular adenosine triphosphate (ATP) levels, thereby activating pathways essential for fibroblast migration and angiogenesis. In a mouse model of infected skin defects, application of the polyP-GA complex (in the form of hydrogel and spray sequentially) significantly accelerated wound closure, enhanced collagen deposition and neovascularization, and promoted functional tissue remodeling. This work demonstrates that the minimalist therapeutic design, built on the synergistic pairing of biocompatible but otherwise subtherapeutic agents polyP and GA, can effectively break the cycle of infection-driven regenerative arrest, achieving high performance in promoting the healing of infected skin defects.

Diabetic bone defects pose a significant clinical challenge due to impaired healing under hyperglycemia. However, no effective therapy is available to treat diabetic bone defect in clinic. This study engineers a biomimetic 3D-printed scaffold for diabetic bone regeneration by integrating glucose oxidase-mineralized amorphous calcium phosphate (GOx@ACP) nanoparticles into a gelatin methacryloyl (GelMA) hydrogel. Biomineralization encapsulates GOx within ACP, enhancing enzymatic stability and enabling glucose-responsive degradation. The scaffold exerts dual therapeutic actions consuming glucose to alleviate hyperglycemia while generating trace H₂O₂ to promote angiogenesis, alongside releasing osteogenic ions (Ca²⁺/PO₄³⁻) upon ACP degradation. The scaffold’s sustained degradation profile (with 61.02

Effective repair of peripheral nerve injury (PNI) depends on the scaffold orientation and immunomodulatory capabilities of functionalized scaffolds, both of which substantially influence nerve regeneration. In this study, composite nerve scaffolds incorporating astaxanthin (AXT) and polycaprolactone (PCL) are developed to investigate the influence of scaffold orientation and blend concentration on cellular behavior, including adhesion, migration, and proliferation. In vitro analysis identifies 0.2% AXT/PCL fabricated at a rotational speed of 400 rpm as the optimal configuration for facilitating directed cell growth and guiding nerve repair. Moreover, the controlled release of AXT improves the microenvironment by preserving mitochondrial homeostasis, promoting mitophagy, and reducing oxidative stress and inflammation. In vivo assessments reveal that the AXT/PCL group (0.2% AXT/PCL‐400) achieves better morphological, histological, electrophysiological, and functional recovery than the PCL, AXT/PCL+M0, and AXT/PCL+M4 groups, approaching the outcomes observed in the autograft (Auto) group. Moreover, the AXT/PCL+M4 group demonstrates better regenerative outcomes than the PCL and AXT/PCL+M0 groups, underscoring the critical role of mitophagy in regulating the regenerative microenvironment.

Sarcopenia, a progressive skeletal muscle disorder marked by loss of mass and function, presents growing societal challenges due to limited therapeutic options. Here, we identify mitochondrial dysfunction and oxidative stress as central drivers of sarcopenia through integrated bioinformatics and clinical validation. To address this pathophysiology, we engineer a muscle-targeted nanocomposite (BP-PEG-MOTS-c, BM) combining mitochondrial-derived peptide MOTS-c with antioxidant black phosphorus nanosheets (BP). BM exhibits dual functionality: MOTS-c restores mitochondrial function, while BP synergistically amplifies ROS scavenging capacity. In cellular and murine models with age-related sarcopenia, BM treatment alleviates muscle dysfunction and muscle loss, concurrently normalizing mitochondrial function and reducing lipid peroxidation. Mechanistic profiling via RNA-seq reveals BM's activation of PI3K/AKT/Nrf2 and suppression of ROS/p38 MAPK signaling pathway, mediating antioxidant responses and maintenance of mitochondrial homeostasis. The nanocomposite demonstrats superior biocompatibility in toxicity assays, outperforming conventional delivery systems. Our findings establish that BM has been established as a promising mitochondrial redox modulator with translational potential for sarcopenia and related age-associated pathologies.

Radiotherapy induced skin defect (RISD) is a severe radiotherapy complication with persistent oxidative stress and recurrent excessive reactive oxygen species (ROS), impeding normal tissue repair processes. Nevertheless, the lack of a standardized animal model severely hinders the progress of related research work. We develop a novel strategy for repairing the RISD microenvironment, which combines initial ROS clearance, subsequent inhibition of ROS production and the repair of proliferation related cell pathways/functions. As a proof of concept, a composite microneedle (MN) patch comprising γ‐polyglutamic acid as the base and ruthenium (Ru) clusters modified magnesium silicate nanosheets (MSR NSs) as the enzyme‐like component is prepared. The Ru clusters have excellent ROS scavenging ability and help activate the peroxisome proliferators activated receptor signaling pathway confirmed by the sequencing analysis while the magnesium silicate is degraded under physiological conditions to release magnesium ions and silicate ions, enhancing cell proliferation, migration, and angiogenesis ability. The radiation induced skin defect animal model is established to evaluate the RISD repair efficacy of our MSR@MN patch in comparison with γPGA‐MSR ointment and commercial product Orgotein. The results show that our MSR@MN patch effectively improves the pathological microenvironment of abnormal ROS accumulation, reduces inflammatory response and promotes mature angiogenesis and tissue remodeling.

Dentin hypersensitivity caused by the exposure of dentinal tubules is affecting a significant portion of the population. With promising prospects, the biomimetic mineralization materials used in treating dentin hypersensitivity are expected to possess a metastable characteristic, for which they can easily penetrate the tubules and the surrounding tissues, but then occlude them via a transformation of size and phase immediately. Herein, this study develops a metastable calcium phosphate cluster (MCPC)-involved mineralization process, which is regulated by dual biological macromolecules: bovine serum albumin (BSA) and poly-L-lysine (PLL). BSA functions to stabilize the primary calcium phosphate clusters; PLL further tunes the cluster's evolution (toward larger and crystalline particles) into a metastable fashion, and meanwhile inhibits the local bacteria. Upon treatments, the system generates amorphous MCPC with ultrasmall size (1-2 nm); then they enter the deep dentinal tubules, subsequently aggregate and crystalline into immobile larger particles, which finally seal the exposed dentinal tubules. The effective occlusion of dentinal tubules as well as significant antibacterial performance are confirmed both in vivo and in vitro. This study has devised not only a regulatory approach for the evolution of mineralization-active clusters but also established an efficient method for managing dentin hypersensitivity.

Peri-implantitis is the main reason for dental implant failure. Optimizing electroactivity at the interface between dental implants and tissue is essential for enhancing integration and preventing bacterial invasion. Here, a bioinspired piezoelectric-conductive integrated peri-implant gingiva (PiG) with simultaneously enhanced antibacterial efficacy and soft-tissue integration, which is based on a flexible piezoelectric film and conductive polymer network, is presented. The piezoelectricity of PiG is achieved through the electrospinning of polyvinylidene fluoride/BaTiO3/MXene on a polydopamine-modified plasma-activated Ti surface, whereas the conductive property of PiG is achieved by the in situ polymerization of 3,4-ethylenedioxythiophene monomers. Under ultrasonic irradiation, PiG can promote the formation of neutrophil extracellular traps and reactive oxygen species, thus achieving synergistic and efficient piezodynamic killing of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Additionally, piezoelectricity-enabled electrical stimulation endows PiG with enhanced fibroblasts adhesion, proliferation, and collagen secretion. As a demonstration, ultrasound irradiation of PiG-grafted Ti implanted in a subcutaneous implantation rat model efficiently eliminates the S. aureus infection and rescues the implant with increased soft-tissue integration. The concept of an artificial PiG is anticipated to open new avenues for the development of high-performance implant materials, potentially extending their lifespans.