A Novel Approach to Enhance Bone Regeneration by Controlling the Polarity of GaN/AlGaN Heterostructures

Rapid and effective bone regeneration is still a major challenge in the clinical treatment of various bone diseases. Although recently developed electroactive materials have demonstrated high bone regeneration potential, the instability of the electrical stimulation and the unclear effects of the charge polarity on osteogenic differentiation hinder their clinical applications. In this work, GaN/AlGaN materials with well-controlled polarity are used for the first time to induce endogenous electric stimulation and facilitate bone regeneration. By controlling the direction and magnitude of the piezoelectric and spontaneous polarization in the functional layer (GaN), charged GaN/AlGaN surfaces of opposite polarity, whose zeta potentials are within the range of the physiological potential, are obtained. Compared with N-polarity GaN/AlGaN (with a positively charged surface), Ga-polarity GaN/AlGaN (with a negatively charged surface) nanofilms show rapid and superior bone repair in vivo. In addition, the Ga-polarity GaN/AlGaN hetero-structures significantly promote the attachment, spreading, recruitment, and osteogenic differentiation of bone mesenchymal stem cells in vitro. Moreover, the bone morphogenetic protein-6 (BMP6) expression profile in the early stages of osteogenic differentiation reveals that BMP6 may be an electrically sensitive osteogenic protein. This work sheds light on the application of III-nitride materials in bone regeneration.     

0D/1D Heterojunction Implant with Electro-Mechanobiological Coupling Cues Promotes Osteogenesis

Mimicking the natural bone extracellular matrix containing intrinsic topography and electrical signals is an effective way to modulate bone regeneration. However, simultaneously coupling of the intrinsic mechanobiology and electrical cues of implant to modulate bone regeneration remains ignored. Here, the authors report in situ designation of titanium dioxide (TiO₂) nanocone/bismuth oxide (Bi₂O₃) nanodot heterojunctions on bone implant surface to electro-biomechanically trigger osseointegration at bone/implant interface. TiO₂ nanocone/Bi₂O₃ nanodot heterojunctions exhibit built-in electric field at the nanoscale interface and elastic modulus equivalent to that of bone tissue. The nano-heterojunctions significantly promoted the attachment, spreading, and osteogenic differentiation of bone marrow mesenchymal stem cells in vitro, and the osteogenesis in vivo. The authors also show that the effects of nano-heterojunctions on osteogenesis are mediated by yes-associated protein biomechanical signal pathway and intracellular enrichment induced Phosphatidylinositol 3-kinase signal pathway. Their findings highlight the coupling of topographical and electric parameters of biomaterials for modulating cell behaviors.     

Hydrophobic Coating Platforms for High-Efficiency Loading and Direct Transmembrane Delivery of Fat-Soluble Osteogenic Drug for Enhanced Osseointegration of Titanium Implants

Compared with water-soluble osteogenic drugs, fat-soluble osteogenic drugs exhibit higher bioavailability and drug stability, making them valuable for enhancing the osseointegration of implants. However, existing drug-loading coatings are primarily designed for water-soluble drugs, limiting their effectiveness in loading and delivering fat-soluble osteogenic drugs. This study employed alkali treatment, silanization, and oleic acid acylation to sequentially modify the surface of Ti alloy, aiming to fabricate surfaces capable of efficiently loading and delivering fat-soluble osteogenic drugs. Results show that the hydrophilicity and loading capacity of fat-soluble osteogenic drugs strongly depended on the duration of the acylation treatment. Furthermore, the drug release mechanism involved direct diffusion from the coating to the cells in contact, resulting in improved bioavailability, as opposed to diffusion into the surrounding medium and subsequent cellular uptake. In vitro experiments using vitamine D3 (VD₃) as a model drug confirmed that the coating effectively promoted bone formation through the highly efficient delivery of VD₃. Furthermore, in vivo experiments demonstrated that the VD₃-loaded lipophilic surface significantly enhanced osteogenic capability and improved the osseointegration of titanium implants. This study provides a promising strategy for loading fat-soluble drugs onto Ti implants and direct experimental evidence demonstrating the significant value of fat-soluble drugs in promoting implant osseointegration.     

Self‐Adaptive Antibacterial Porous Implants with Sustainable Responses for Infected Bone Defect Therapy

The development of responsive antibacterial implants is highly significant for the treatment of implant‐associated infection. In this study, one self‐adaptive antibacterial porous implant with sustainable responses is flexibly designed and constructed for infected bone defect therapy. Porous hydroxyapatite (HA) implants derived from nature bones, one typical implant, are first functionalized via low‐cytotoxic ethanediamine‐functionalized poly(glycidyl methacrylate) brushes, and gentamicin sulfate (GS, a kind of aminoglycoside antibiotic in clinic) is subsequently conjugated by an acid‐responsive bond to produce smart antibacterial HA implants (HA–GS). The release of GS can be triggered by the acidic environment induced by the metabolism of bacteria for self‐adaptive antibacterial response. Due to the good drug loading capacity and chemical stability of HA–GS in neutral condition, the sustainable antibacterial ability is readily achieved for long‐term applications. The highly effective in vivo anti‐infection therapy with HA–GS is demonstrated in one infected bone defect rabbit model. The implant‐associated infection is completely inhibited by HA–GS at the early stage and the defected bones exhibit superior recovery at the late stage. This design strategy of sustainable self‐adaptive antibacterial implants will provide a promising concept for the prevention and therapy of implant‐associated infections.     

Field distributions in the rat tibia with and without a porousimplant during electrical stimulation: a parameteric modeling

Expeditious post-operative ingrowth of bone is necessary for clinically successful fixation of porous joint prostheses. Electrical or electromagnetic fields to stimulate bone growth into porous implants have been used; however, they produced nonconvincing data. This was partially attributable to the lack of quantification of the localized electric fields produced in the pores of the implants. Therefore, this study set out: i) to quantify the local electric field values induced into the surface pores of nonconducting implants by "capacitive" coupling and to determine the magnitude of the macroscopically applied capacitively coupled electrical currents to induce specific electric field amplitudes in the pores, ii) to identify the important dielectric properties of the implant-tissue interface, and iii) to create the basis for successfully applying electrical fields in an animal model to stimulate bone ingrowth. A finite element method was used to calculate the electric field gradients and current densities present in a rat tibia modeled with a porous intramedullary implant when capacitively stimulated. Results indicated that while the current density in the pores are reduced in comparison to the region just outside the pore by about one order of magnitude, a significant current density still exists in the pore region. Furthermore, the presence of the implant increases the current densities in the trabecular bone while decreasing these values in the cortical bone. Replacing the trabecular bone in the pore by saline increases the current density in the pore by three-fold, but decreases the voltage gradient by a similar factor.     

Ferroelectric Domain Wall Memristor

A domain wall‐enabled memristor is created, in thin film lithium niobate capacitors, which shows up to twelve orders of magnitude variation in resistance. Such dramatic changes are caused by the injection of strongly inclined conducting ferroelectric domain walls, which provide conduits for current flow between electrodes. Varying the magnitude of the applied electric‐field pulse, used to induce switching, alters the extent to which polarization reversal occurs; this systematically changes the density of the injected conducting domain walls in the ferroelectric layer and hence the resistivity of the capacitor structure as a whole. Hundreds of distinct conductance states can be produced, with current maxima achieved around the coercive voltage, where domain wall density is greatest, and minima associated with the almost fully switched ferroelectric (few domain walls). Significantly, this “domain wall memristor” demonstrates a plasticity effect: when a succession of voltage pulses of constant magnitude is applied, the resistance changes. Resistance plasticity opens the way for the domain wall memristor to be considered for artificial synapse applications in neuromorphic circuits.     

Space‐Charge‐Stabilized Ferroelectric Polarization in Self‐Oriented Croconic Acid Films

Great progress has been made recently in molecular ferroelectrics with properties even comparable to those of inorganic ferroelectrics. However, it is difficult to develop basic thin films and devices for practical applications since most molecular ferroelectrics are uniaxial. The single polar axes of crystallites inside their films, if available, are usually oriented randomly. These can induce the components without contribution to ferroelectric polarization and a large depolarization electric field to suppress polarization. In this work, it is demonstrated that uniaxial croconic acid films in two‐terminal devices, deposited by thermal evaporation, can show effective ferroelectric polarization and nonvolatile memory switching behavior with small coercive fields of 11–30 kV cm^?1. The polar c‐axes in thick crystalline films (>500 nm) are found to be self‐oriented nearly at a desired direction. With the assistance of trapped charges, stable ferroelectric polarization can be achieved, in spite of the existence of nonferroelectric components. These may pave a way to utilize uniaxial molecular ferroelectrics for various applications, such as gate dielectrics, electrets, and memory devices.     

Direct Observation of Ferroelectric Domain Walls in LiNbO3: Wall‐Meanders,Kinks, and Local Electric Charges

Direct observations of the ferroelectric domain boundaries in LiNbO₃ are performed using high‐resolution high‐angle annular dark field scanning transmission electron microscopy imaging, revealing a very narrow width of the domain wall between the 180° domains. The domain walls demonstrate local side‐way meandering, which results in inclinations even when the overall wall orientation follows the ferroelectric polarization. These local meanders contain kinks with “head‐to‐head” and “tail‐to‐tail” dipolar configurations and are therefore locally charged. The charged meanders are confined to a few cation layers along the polarization direction and are separated by longer stretches of straight domain walls.     

Continuous Control of Charge Transport in Bi‐Deficient BiFeO3 Films Through Local Ferroelectric Switching

It is demonstrated that electric transport in Bi‐deficient Bi_1‐δFeO₃ ferroelectric thin films, which act as a p‐type semiconductor, can be continuously and reversibly controlled by manipulating ferroelectric domains. Ferroelectric domain configuration is modified by applying a weak voltage stress to Pt/Bi_1‐δFeO₃/SrRuO₃ thin‐film capacitors. This results in diode behavior in macroscopic charge‐transport properties as well as shrinkage of polarization‐voltage hysteresis loops. The forward current density depends on the voltage stress time controlling the domain configuration in the Bi_1‐δFeO₃ film. Piezoresponse force microscopy shows that the density of head‐to‐head/tail‐to‐tail unpenetrating local domains created by the voltage stress is directly related to the continuous modification of the charge transport and the diode effect. The control of charge transport is discussed in conjunction with polarization‐dependent interfacial barriers and charge trapping at the non‐neutral domain walls of unpenetrating tail‐to‐tail domains. Because domain walls in Bi_1‐δFeO₃ act as local conducting paths for charge transport, the domain‐wall‐mediated charge transport can be extended to ferroelectric resistive nonvolatile memories and nanochannel field‐effect transistors with high performances conceptually.     

Unraveling Deterministic Mesoscopic Polarization Switching Mechanisms: Spatially Resolved Studies of a Tilt Grain Boundary in Bismuth Ferrite

The deterministic mesoscopic mechanism of ferroelectric domain nucleation is probed at a single atomically‐defined model defect: an artificially fabricated bicrystal grain boundary (GB) in an epitaxial bismuth ferrite film. Switching spectroscopy piezoresponse force microscopy (SS‐PFM) is used to map the variation of local hysteresis loops at the GB and in its immediate vicinity. It is found that the the influence of the GB on nucleation results in a slight shift of the negative nucleation bias to larger voltages. The mesoscopic mechanisms of domain nucleation in the bulk and at the GB are studied in detail using phase‐field modeling, elucidating the complex mechanisms governed by the interplay between ferroelectric and ferroelastic wall energies, depolarization fields, and interface charge. The combination of phase‐field modeling and SS‐PFM allows quantitative analysis of the mesoscopic mechanisms for polarization switching, and hence suggests a route for unraveling the mechanisms of polarization switching at a single defect level and ultimately optimizing materials properties through microstructure engineering.     

Electric‐Field‐Controlled Alignment of Rod‐Shaped Fluorescent Nanocrystals in Smectic Liquid Crystal Defect Arrays

Periodic micro‐arrays of straight linear defects containing nanoparticles can be created over large surface areas at the transition from the nematic to smectic‐A phase in a nanoparticle–liquid crystal (LC) composite material confined under the effect of conflicting anchoring conditions (unidirectional planar vs normal) and electric fields. Anisomeric dichroic dye molecules and rod‐shaped fluorescent semiconductor nanocrystals (dot‐in‐rods) with large permanent electric dipole and high linearly polarized photoluminescence quantum yield align parallel to the local LC molecular director and follow its reorientation under application of the electric field. In the nano‐sized core regions of linear defects, where the director is undefined, anisotropic particles align parallel to the defect whereas spherical quantum dots do not show any particular interaction with the defect. Under application of an electric field, ferroelectric semiconductor nanoparticles in the core region align along the field, perpendicular to the defect direction, whereas dichroic dyes remain parallel to the defect. This study provides useful insights into the complex interaction of anisotropic nanoparticles and anisotropic soft materials such as LCs in the presence of external fields, which may help the development of field‐responsive nanoparticle‐based functional materials.     

Room‐Temperature Nonvolatile Memory Based on a Single‐Phase Multiferroic Hexaferrite

The cross‐coupling between electric polarization and magnetization in multiferroic materials provides a great potential for creating next‐generation memory devices. Current studies on magnetoelectric (ME) applications mainly focus on ferromagnetic/ferroelectric heterostructures because single‐phase multiferroics with strong magnetoelectric coupling at room temperature are still very rare. Here a type of nonvolatile memory device is presented solely based on a single‐phase multiferroic hexaferrite Sr₃Co₂Fe₂₄O₄₁ which exhibits nonlinear magnetoelectric effects at room temperature. The principle is to store binary information by employing the states (magnitude and sign) of the first‐order and the second‐order magnetoelectric coefficients (α and β), instead of using magnetization, electric polarization, and resistance. The experiments demonstrate repeatable nonvolatile switch of α and β by applying pulsed electric fields at room temperature, respectively. Such kind of memory device using single‐phase multiferroics paves a pathway toward practical applications of spin‐driven multiferroics.     

A Ferroelectric Ferromagnetic Composite Material with Significant Permeability and Permittivity

Composite materials containing both ferroelectric and ferromagnetic phases have been synthesized from nanometer‐sized powders of BaTiO₃ (ferroelectric phase) and NiCuZn ferrite (ferromagnetic phase) by a standard ceramic method. The coexistence of magnetic and electric hysteresis in the composite material has been observed at room temperature. Upon the application of magnetic and electric fields, the magnetization and electric polarization of the composite material can easily be tuned based on the changing BaTiO₃ content of the materials studied. These composite materials exhibit both excellent dielectric and soft‐magnetic properties with a variation of the frequency. Our results strongly suggest that this composite material may be the best candidate for the development of truly integrated passive filters. Due to the combination of both inductance and capacitance in one material, the adoption of an integrated passive filter could greatly reduce the size of printed circuit boards and could efficiently suppress electromagnetic interference, thereby enabling significant miniaturization of electronic elements and devices.     

Boosting Photocurrent via Heating BiFeO3 Materials for Enhanced Self‐Powered UV Photodetectors

BiFeO₃ (BFO) is a potentially important Pb‐free ferroelectric with a narrow bandgap and is expected to become a novel photodetector. The photocurrent in BFO₃ strongly depends on the temperature but only a few studies have investigated in detail the relationships between photocurrent and temperature. Here, the temperature‐dependent photocurrent and the corresponding photosensing properties of a Ag/BFO/indiumtin oxide (ITO) photodetector based on an optimized planar‐structured electrode configuration are investigated. The photocurrent and responsivity of the BFO₃‐based photodetector can first be increased and then be decreased with increasing temperature. The largest photocurrent and responsivity can reach 51.5 µA and 6.56 × 10^?4 A W^?1 at 66.1 °C, which is enhanced 126.3% as compared with that at room temperature. This may be caused by the temperature‐modulated bandgap and barrier height in Ag/BFO/ITO device. This study clarifies the relationship between photosensing performance and the operating temperature of BFO‐based photodetector and will push forward the application of ferroelectric materials in photoelectric field.     

Switching On and Off Macrophages by a “Bridge-Burning” Coating Improves Bone-Implant Integration under Osteoporosis

Osteoporosis poses substantial challenges for biomaterials implantation. New approaches to improve bone-implant integration should resolve the fundamental dilemma of inflammation—proper inflammation is required at early stages but should be suppressed later for better healing, especially under osteoporosis. However, precisely switching on and off inflammation around implants in vivo remains unachieved. To address this challenge, a “bridge-burning” coating material that comprises a macrophage-activating glycan covalently crosslinked by a macrophage-eliminating bisphosphonate to titanium implant surface is designed. Upon implantation, the glycan instructs host macrophages to release pro-osteogenic cytokines (“switch-on”), promoting bone cell differentiation. Later, increasingly mature bone cells secrete alkaline phosphatase to cleave the glycan-bisphosphonate complexes from the implant, which in turn selectively kill the proinflammatory macrophages (“switch-off”) that have completed their contribution—hence in the manner of “burning bridges”—to promote healing. In vivo examination in an osteoporotic rat model demonstrates that this coating significantly enhances bone-implant integration (88.4% higher contact ratio) through modulating local inflammatory niches. In summary, a bioresponsive, endogenously triggered, smart coating material is developed to sequentially harness and abolish the power of inflammation to improve osseointegration under osteoporosis, which represents a new strategy for designing immunomodulatory biomaterials for tissue regeneration.     

Self-Tandem Bio-Heterojunctions Empower Orthopedic Implants with Amplified Chemo-Photodynamic Anti-Pathogenic Therapy and Boosted Diabetic Osseointegration

Hyperglycemic microenvironment in diabetes mellitus inevitably stalls the normal orchestrated course of bone regeneration and encourages pathogenic multiplication. Photodynamic therapy (PDT) and chemo-dynamic therapy (CDT) are extensively harnessed to combat pathogens, yet deep-seated diabetic bone defect has difficulty in supplying sufficient oxygen (O₂) and hydrogen peroxide (H₂O₂) stocks, resulting in inferior therapeutic efficiency. To address the tough plaguing, the self-tandem bio-heterojunctions (bio-HJs) consisting of molybdenum disulfide (MoS₂), graphene oxide (GO), and glucose oxidase (GOx) are constructed on orthopedic polyetheretherketone (PEEK) implants (SP-Mo/G@GOx) for amplified chemo-photodynamic anti-pathogenic therapy and boosted osseointegration in the deep-seated diabetic micromilieu. In this system, GOx exhausts glucose to generate H₂O₂, which provides an abundant stock for CDT. Besides, the bio-HJs produce hyperthermia upon near-infrared light (NIR) to accelerate the dynamic process, which amplifies the antibacterial potency of PDT by promoting the vast yield of singlet oxygen (¹O₂) in a self-tandem manner. More importantly, in vivo and in vitro assays demonstrate that the engineered implants exert a captivated bactericidal ability and significantly boost osseointegration in an infectious diabetic bone defect model. As envisaged, this study furnishes a novel tactic to arm orthopedic implants with self-tandem capability for the remedy of infectious diabetic bone defects.     

Establishing multiscale models for simulating whole limb estimates of electric fields for osseointegrated implants

Although the survival rates of warfighters in recent conflicts are among the highest in military history, those who have sustained proximal limb amputations may present additional rehabilitation challenges. In some of these cases, traditional prosthetic limbs may not provide adequate function for service members returning to an active lifestyle. Osseointegration has emerged as an acknowledged treatment for those with limited residual limb length and those with skin issues associated with a socket together. Using this technology, direct skeletal attachment occurs between a transcutaneous osseointegrated implant (TOI) and the host bone, thereby eliminating the need for a socket. While reports from the first 100 patients with a TOI have been promising, some rehabilitation regimens require 12-18 months of restricted weight bearing to prevent overloading at the bone-implant interface. Electrically induced osseointegration has been proposed as an option for expediting periprosthetic fixation and preliminary studies have demonstrated the feasibility of adapting the TOI into a functional cathode. To assure safe and effective electric fields that are conducive for osseoinduction and osseointegration, we have developed multiscale modeling approaches to simulate the expected electric metrics at the bone-implant interface. We have used computed tomography scans and volume segmentation tools to create anatomically accurate models that clearly distinguish tissue parameters and serve as the basis for finite element analysis. This translational computational biological process has supported biomedical electrode design, implant placement, and experiments to date have demonstrated the clinical feasibility of electrically induced osseointegration.     

Nanofragmentation of Ferroelectric Domains During Polarization Fatigue

The microscopic mechanism for polarization fatigue in ferroelectric oxides has remained an open issue for several decades in the condensed matter physics community. Even though numerous models are proposed, a consensus has yet to be reached. Since polarization reversal is realized through ferroelectric domains, their behavior during electric cycling is critical to elucidating the microstructural origin for the deteriorating performance. In this study, electric field in situ transmission electron microscopy is employed for the first time to reveal the domain dynamics at the nanoscale through more than 10³ cycles of bipolar fields. A novel mechanism of domain fragmentation is directly visualized in polycrystalline [(Bi_1/2Na_1/2)_0.95Ba_0.05]_0.98La_0.02TiO₃. Fragmented domains break the long‐range polar order and, together with domain wall pinning, contribute to the reduction of switchable polarization. Complimentary investigations into crystal structure and properties of this material corroborate our microscopic findings.     

Finite‐Temperature Properties of Rare‐Earth‐Substituted BiFeO3 Multiferroic Solid Solutions

Rare‐earth substitution in the multiferroic BiFeO₃ (BFO) material holds promise for resolving drawbacks inherent to pure BFO, and for enhancing piezoelectric and magneto‐electric properties via a control of structural and magnetic characteristics. Rare‐earth‐doped BFO solid solutions also exhibit unresolved features, such as the precise nature and atomic characteristics of some intermediate phases. Here, an effective Hamiltonian scheme is developed that allows the investigation of finite‐temperature properties of these systems from an atomistic point of view. In addition to reproducing experimental results of Nd‐doped BFO on structural and magnetic transitions with temperature and composition, this scheme also provides an answer (in form of nanotwins) to these intermediate phases. A striking magneto‐electric effect—namely a paramagnetic–to–antiferromagnetic transition that is induced by an applied electric field—is further predicted near critical compositions, with the resulting structural path being dependent on the orientation of the electric field relative to the antiferroelectric vector.     

Observation of a Negative Thermal Hysteresis in Relaxor Ferroelectric Polymers

Hysteresis phenomena, including both electrical and thermal types, are essential to ferroelectric materials. The former, known as polarization‐electric field hysteresis, has been intensively studied in a wide range of ferroelectric materials. However, relevant experimental evidence on thermal hysteresis remains limited, especially in ferroelectric polymers, even though thermal hysteresis is crucial to the caloric effect, which is usually the largest near the phase transition. Here, the thermal hysteresis behavior in ferroelectric polymers is studied in terms of temperature‐dependent polarization upon heating and cooling. In contrast to common belief, a negative thermal hysteresis is observed in relaxor ferroelectric polymers, which is probably due to local stabilization of ferroelectric distortion induced by electric field. Using the polymer blend as a platform, it is further shown that the negative thermal hysteresis arises at the disappearance of long‐range ferroelectric distortion and the thermal hysteresis behavior may be effectively controlled through the blend approach. This study not only provides deeper insights into electrocaloric effect in ferroelectric polymers but also offers an approach to study the critical phenomenon in a ferroelectric system.