Regenerative Mechanism Research Articles

Sall4 and Gata4 induce cardiac fibroblast transition towards a partially multipotent state with cardiogenic potential

Cardiac cellular fate transition holds remarkable promise for the treatment of ischemic heart disease. We report that overexpressing two transcription factors, Sall4 and Gata4, which play distinct and overlapping roles in both pluripotent stem cell reprogramming and embryonic heart development, induces a fraction of stem-like cells in rodent cardiac fibroblasts that exhibit unlimited ex vivo expandability with clonogenicity. Transcriptomic and phenotypic analyses reveal that around 32 ± 6.4% of the expanding cells express Nkx2.5, while 13 ± 3.6% express Oct4. Activated signaling pathways like PI3K/Akt, Hippo, Wnt, and multiple epigenetic modification enzymes are also detected. Under suitable conditions, these cells demonstrate a high susceptibility to differentiating into cardiomyocyte, endothelial cell, and extracardiac neuron-like cells. The presence of partially pluripotent-like cells is characterized by alkaline phosphatase staining, germ layer marker expression, and tumor formation in injected mice (n = 5). Additionally, significant stem-like fate transitions and cardiogenic abilities are induced in human cardiac fibroblasts, but not in rat or human skin fibroblasts. Molecularly, we identify that SALL4 and GATA4 physically interact and synergistically stimulate the promoters of pluripotency genes but repress fibrogenic gene, which correlates with a primitive transition process. Together, this study uncovers a new cardiac regenerative mechanism that could potentially advance therapeutic endeavors and tissue engineering.

Nose-to-brain delivery of stem cells in stroke: the role of extracellular vesicles.

Stem cell transplantation offers a promising therapy that can be administered days, weeks, or months after a stroke. We recognize 2 major mitigating factors that remain unresolved in cell therapy for stroke, notably: (1) well-defined donor stem cells and (2) mechanism of action. To this end, we advance the use of ProtheraCytes, a population of non-adherent CD34+ cells derived from human peripheral blood and umbilical cord blood, which have been processed under good manufacturing practice, with testing completed in a phase 2 clinical trial in post-acute myocardial infarction (NCT02669810). We also reveal a novel mechanism whereby ProtheraCytes secrete growth factors and extracellular vesicles (EVs) that are associated with angiogenesis and vasculogenesis. Our recent data revealed that intranasal transplantation of ProtheraCytes at 3 days after experimentally induced stroke in adult rats reduced stroke-induced behavioral deficits and histological damage up to 28 days post-stroke. Moreover, we detected upregulation of human CD63+ EVs in the ischemic brains of stroke animals that were transplanted with ProtheraCytes, which correlated with increased levels of DCX-labeled neurogenesis and VEGFR1-associated angiogenesis and vasculogenesis, as well as reduced Iba1-marked inflammation. Altogether, these findings overcome key laboratory-to-clinic translational hurdles, namely the identification of well-characterized, clinical grade ProtheraCytes and the elucidation of a potential CD63+ EV-mediated regenerative mechanism of action. We envision that additional translational studies will guide the development of clinical trials for intranasal ProtheraCytes allografts in stroke patients, with CD63 serving as a critical biomarker.

Regenerative Orr mechanism yielding large non-modal perturbation energy growth in a viscosity stratified plane shear flow

Transiently growing non-modal perturbations can play a crucial role in the transition of plane shear flows in modally stable regimes. In terms of the extent of transient amplification, three-dimensional perturbations are typically more prominent due to the lift-up effect. In contrast, two-dimensional (2D) spanwise-independent perturbations are often considered less important as they typically undergo modest levels of transient growth and are short-lived. The Orr mechanism is key to the amplification of energy for 2D perturbations. In this work, we discuss 2D non-modal perturbations of three-layer viscosity stratified flows with the mean shear rates of the outer layers being equal. Strikingly, a novel regenerative Orr mechanism is found that allows for significant amount of energy amplification despite the 2D nature of the perturbations. Moreover, these perturbations survive for considerably long times. The perturbation structure shows symmetry about the middle layer and evolves such that the Orr mechanism can repeatedly occur in a regenerative manner resulting in the perturbation energy evolving in a markedly non-monotonic fashion. When these same perturbations are introduced in a uniform plane shear flow, the corresponding non-modal transient amplifications are shown to be much smaller.

A comparative analysis of square-wave voltammetry and multi-frequency electrochemical Faradaic spectroscopy for kinetic characterisation

A rigorous comparison between square-wave voltammetry (SWV) and the recently proposed multi-frequency electrochemical Faradaic spectroscopy (MEFS) is presented for both a quasireversible electrode reaction of a dissolved redox couple at a planar macroscopic electrode and a catalytic regenerative electrode mechanism (EC′ reaction scheme) by means of numerical simulations. MEFS offers fast kinetic characterisation with a minimal set of experiments, as the system is interrogated with a range of SW frequencies in a single experiment. By changing the mid-potential Em, a critical parameter of MEFS, a broad range of standard rate constants for the heterogeneous interfacial electron transfer is accessible, ranging between 0.006 and 0.12 cm s−1. In the case of the EC′ mechanism, features of the current components in both SWV and MEFS reflect the involvement of the follow-up regenerative chemical reaction (i.e. C′ catalytic step). However, for the kinetic characterisation of the EC′ mechanism, the comparative analysis suggests that SWV should be the main operating technique.

POWERING THE EV WITH DYNAMOS

The dynamo, traditionally used in bicycles to convert mechanical energy into electrical energy, can be adapted for use in EVs to supplement battery power. As the vehicle moves, the dynamo harnesses kinetic energy, converting it into electricity to recharge the EV's battery. This regenerative braking mechanism not only extends the vehicle's range but also reduces reliance on charging stations, enhancing the EV's practicality and autonomy. The integration of a dynamo system introduces a sustainable element by utilizing kinetic energy that would otherwise be dissipated as heat during braking. By capturing and converting this energy, EVs equipped with dynamos can operate more efficiently, reducing overall energy consumption and carbon emissions. This abstract explores the technical feasibility, potential benefits, and challenges associated with implementing a dynamo system in EVs. Considerations such as optimal placement, efficiency optimization, and compatibility with existing battery and electrical systems are discussed. Additionally, the economic viability and environmental impact of widespread adoption of dynamo-equipped EVs are evaluated. The integrating dynamos into EVs presents a promising avenue to address range anxiety and charging infrastructure limitations, while also promoting sustainability and energy efficiency in the transportation sector. Further research and development are warranted to optimize the design and implementation of this innovative solution for powering electric vehicles.

Waste cooking oil as a sustainable solution for UV-aged asphalt binder: Rheological, chemical and molecular structure

Recycling of UV-aged asphalt has been a hot research issue. In this paper, waste cooking oil, plasticizer, toughener, and petroleum resin were used as raw materials for asphalt rejuvenator. This paper explores the effect of regeneration conditions on the regeneration effect of UV-aged asphalt binders through high-temperature rheology and chemical compositions. The paper also attempts to reveal the regeneration mechanism of asphalt binder regeneration using waste cooking oil. Dynamic shear rheology (DSR) and fourier transform infrared (FTIR) spectroscopy assess high-temperature rheological properties and chemical compositions. The Pearson correlation coefficient relates the rheological parameters to the chemical microstructure. And the functional relationship between carbonyl-corrected peak area and aging factor Ai of recycled asphalt and high temperature rheological parameters were established. Molecular simulation investigates WCO-recycled asphalt binder micro-morphology and adsorption mechanisms. The results showed that significant changes in the carbonyl and sulfoxide peak areas affected the high-temperature rheological properties. Regeneration conditions significantly affect asphalt regeneration effectiveness. WCO reduces CO and SO groups, crucial in asphalt viscoelastic behavior. Molecular interaction analysis reveals WCO's regenerative mechanism. This work emphasizes integrating molecular structure, chemical composition, and macroscopic properties in asphalt binder research, providing insights for sustainable pavement practices.

(152) Energy Absorption Simulation During Low Intensity Shockwave Therapy

Abstract Introduction Low intensity shockwave therapy (LiSWT) has been used to treat erectile dysfunction since 2010 by inducing mechanotransduction. The greater the shockwave energy absorbed in cavernosal erectile tissue, the greater the opportunity for mechanotransduction regenerative mechanisms to occur and improve erectile function. Effectiveness of LiSWT depends, in part, on applied energy (mJ/mm2) and number of applications (total shocks). Although intensity of LiSWT energy cannot be arbitrarily increased due to side effects, energy absorption may be improved by performing treatment to an erect vs flaccid penis. Intracavernosal pressure and penile volume are both determinants of velocity of the energy wave in tissue and therefore absorption of shockwave energy in tissue. Intracavernosal penile pressure when erect (100 mmHg) is 16-fold higher than flaccid (6 mmHg), and blood volume when erect (142.6 cm3) is >2 times more than flaccid (62.18 cm3), therefore LiSWT in the erect state with larger blood-filled lacunar spaces should be associated with greater shockwave energy absorption. Use of a symmetry-matched secondary reflector can further increase the energy absorption of each applied shockwave by reflecting the wave back. Objective The aim of this study was to perform a simulation of energy absorption during LiSWT with a reflector in both the flaccid and erect penis. Methods This energy model used the MTS UroGold electrohydraulic shockwave device [Softwave TRT]. When sound waves pass through an interface between 2 media with different impedances, sound propagation can be significantly altered. If impedances of the media are different, part of the sound energy is reflected into the incident medium; the rest of the sound energy is transferred to the second medium. Sound propagation in tissue can be illustrated via computer simulation by mathematically calculating the damping and deflection of the sound wave by different tissue structures. Finite Element Method (FEM) simulation models are particularly suitable for the mathematical description of complex processes of shockwave propagation, such as in the flaccid and erect penis. Based on results, a “prediction” of propagation of LiSWT in tissue is possible. This patient-specific procedure is based on consideration of individual anatomical structures: corporal lacunar spaces and physical-acoustic laws. For FEM modeling of LiSWT propagation, program systems ANSYS, MATLAB and PZFLEX/ONSCALE were used. Results Using the FEM calculation model of the simulation analyses, the shockwave pulse is applied at the bottom edge of the model (Fig 1). It propagates through the erect (Fig 2a) and flaccid (Fig 2b) states, with the most energy absorption in the erect penis, shown in red. The effect of increased penile pressure on energy absorption with a constant volume is shown in Fig 3. Conclusions More energy is absorbed in cavernosal tissue during erection than in the flaccid state, with a further increase in absorption with use of a symmetric reflector. This provides greater opportunity for beneficial mechanotransduction regenerative mechanism due, in part, to increased intracavernosal pressure and tissue volume with larger blood-filled lacunar spaces during erection. LiSWT to treat erectile dysfunction should be more effective when performed in the erect state utilizing a reflector. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: MTS Medical, Softwave TRT.

Electric truck gravity energy storage: An alternative to seasonal energy storage

AbstractThe global shift toward a sustainable and eco‐friendly energy landscape necessitates the adoption of long‐term, high‐capacity energy storage solutions. This research introduces an inventive energy storage concept involving the movement of granular materials from a lower elevation to a higher point within natural terrains such as mountains or excavated mining sites. Electrical energy is employed to charge electric batteries that elevate the granular material, thereby storing potential energy. Subsequently, this material is transported down during the electricity generation phase, and the regenerative braking mechanism converts the gravitational energy to replenish the vehicle's battery. The stored energy within these vehicles is then dispatched during peak demand periods or utilized by the vehicles for other freight transportation purposes. Our findings demonstrate a power cost of 1200 USD/kW, an energy storage expense spanning from 1 to 10 USD/kWh, a levelized cost of storage ranging from 35 to 200 USD/MWh, and a global annual potential of approximately 5.4 PWh. Electric vehicle gravity energy storage showcases its capability to bolster sustainable development by offering seasonal and multi‐year energy storage services.

Axonal regrowth under release ofmyelin-associated glycoprotein: chemotaxis by pioneer Schwann cells andCajal's gigantic clubs.

Myelin-associated glycoprotein (MAG), released from pre-degenerated distal nerves following axotomy, blocks the regrowth of sprouts and naked axons. Ensheathed axons, however, continue to elongate and reach MAG-releasing distal nerves. To determine the regenerative mechanism of ensheathed axons without navigators of axonal growth cones by the film model method, we inserted a MAG-releasing distal nerve segment treated with liquid nitrogen (N2DS) between the two films, facing the proximal end of the common peroneal nerves in mice transected 4 days earlier for axons to become ensheathed. On the third postoperative day (Day 3), axon fascicles, subjected to silver staining, extended toward N2DS but with few branches, forming terminal swellings called Cajal's gigantic clubs (CGCs) that are filled with axonal growth cones. Filter paper wetted with either 250 pg/ml MAG or N2DS showed the same configurations when inserted between the two films. This effect was lost following anti-MAG treatment; fascicles strayed near the parent nerve with numerous branches, formed a net of axons and tapered toward thin tips at their ends, just like controls without N2DS. Schwann cell bundles on Day 3 detected with anti-S100, formed sheaths of CGCs at their ends and connected to pioneer Schwann cells (pSCs). To analyze the physiology of Schwann cells, independent of axons, the parent nerve transected 4 days prior was crushed. On Day 2, with pSCs ahead, Schwann cell bundles extended toward N2DS. On Day 4, main bundles regressed, leaving pSCs motionless. Thus, MAG is a candidate chemoattractant for both pSCs and CGCs.

A Review of Advanced Biomaterials and Cells for the Production of Bone Organoid

Rapid advancements in traditional bone tissue engineering have led to innovation in bone repair models and the resolution of insurmountable clinical issues like graft scarcity. The pathophysiological process of treating bone disease, however, is a multidimensional and multimodal regenerative regulatory mechanism that includes numerous immune, inflammatory, or metabolic responses related to the graft or the organism itself. Based on a 3D in vitro cell culture system that is remarkably identical to the body's bone tissue, the bone organoid is a biomimicking bone organ environment. It can accurately mimic the actual repair and regeneration condition in vivo because it shares the same physiological function, structure, morphology, and metabolic process as endogenous bone tissue. As a disruptive regenerative medicine technology, it has wide application prospects in the fields of organ development, gene editing, disease modeling, and precision therapy. Herein, the development process and physiological basis of different cell‐based bone organoids are reviewed, the current status of the application of different materials, cells, and construction methods for building bone organoids is described, and the prospects and challenges for the development of bone organoids in future medical fields is discussed.

Application of a Magnetic Platform in α6 Integrin-Positive iPSC-TM Purification.

The emergence of induced pluripotent stem cell (iPSC) technology has provided a new approach to regenerating decellularized trabecular meshwork (TM) in glaucoma. We have previously generated iPSC-derived TM (iPSC-TM) using a medium conditioned by TM cells and verified its function in tissue regeneration. Because of the heterogeneity of iPSCs and the isolated TM cells, iPSC-TM cells appear to be heterogeneous, which impedes our understanding of how the decellularized TM may be regenerated. Herein, we developed a protocol based on a magnetic-activated cell sorting (MACS) system or an immunopanning (IP) method for sorting integrin subunit alpha 6 (ITGA6)-positive iPSC-TM, an example of the iPSC-TM subpopulation. We first analyzed the purification efficiency of these two approaches by flow cytometry. In addition, we also determined cell viability by analyzing the morphologies of the purified cells. To conclude, the MACS-based purification could yield a higher ratio of ITGA6-positive iPSC-TM and maintain a relatively higher cell viability than the IP-based method, allowing for the preparation of any iPSC-TM subpopulation of interest and facilitating a better understanding of the regenerative mechanism of iPSC-based therapy.

Specific Activation of Yamanaka Factors via HSF1 Signaling in the Early Stage of Zebrafish Optic Nerve Regeneration.

In contrast to the case in mammals, the fish optic nerve can spontaneously regenerate and visual function can be fully restored 3-4 months after optic nerve injury (ONI). However, the regenerative mechanism behind this has remained unknown. This long process is reminiscent of the normal development of the visual system from immature neural cells to mature neurons. Here, we focused on the expression of three Yamanaka factors (Oct4, Sox2, and Klf4: OSK), which are well-known inducers of induced pluripotent stem (iPS) cells in the zebrafish retina after ONI. mRNA expression of OSK was rapidly induced in the retinal ganglion cells (RGCs) 1-3 h after ONI. Heat shock factor 1 (HSF1) mRNA was most rapidly induced in the RGCs at 0.5 h. The activation of OSK mRNA was completely suppressed by the intraocular injection of HSF1 morpholino prior to ONI. Furthermore, the chromatin immunoprecipitation assay showed the enrichment of OSK genomic DNA bound to HSF1. The present study clearly showed that the rapid activation of Yamanaka factors in the zebrafish retina was regulated by HSF1, and this sequential activation of HSF1 and OSK might provide a key to unlocking the regenerative mechanism of injured RGCs in fish.

Ayurvedic Emphasis in Duchenne Muscular Dystrophy: A Case Study

Duchenne muscular dystrophy is one of the most common dystrophinopathies known. It is the most common hereditary neuromuscular disorder and is inherited in an X-linked recessive manner. Incidence is 1:3500 live male infants, characterised by progressive weakness of a selective group of muscles without involvement of nervous system. Age of onset being 3-10 years, many children unable to walk before 18 months of age. The patient usually dies by 18-20 years of age. 80% carries have high CPK values with female being the one. Dystrophin gene is the largest human gene with 79 exons, codes for protein dystrophin required for stabilisation of protein complex at sarcolemma, the abnormal DMD gene is on X chromosome at Xp21 locus. Dystrophin deficiency thus, leads to destruction of muscle fibres and progressive muscular weakness. Corticosteroids are the only medications that have shown to alter the course of DMD but have side effects like weight gain, decreased appetite, increase changes of cataract and osteoporosis. The present study is about management 8 years old male child with B/L lower limb weakness and calf muscle hypertrophy.etc, so according to Ayurvedic management with Panchkarma procedures and internal medicines given the case was managed. Successful improvement in CPK values along with the signs and symptoms was observed. As per Ayurvedic Siddhant and Samprapti application considering Adibalapravrittavyadhi and the Beejabhaga avayava dushti the management done. There is no treatment in any system of medicine and prognosis being unpreventable, Ayurveda instills a regenerative mechanism in neuromuscular disorders with special concern of Panchkarma, Rasayanas, Rasa aushadhi, etc. By this the deterioration can effectively be prolonged and quality of life improved.

Dopamine‐Integrated Nanointerface between Fibrillar Matrix and Hydrophilic Nanohydroxyapatite Regulates Immune Microenvironment to Boost Endogenous Bone Regeneration

AbstractDriving endogenous bone regeneration by cell‐ and factor‐free biomaterials is the most ideal repair strategy. Herein, hybrid interleaved scaffold (HDSH) with nanosized interfacial integration is assembled by organic/inorganic interactive bonding at the nanoscale. With the help of transcriptome and proteome analysis, the regenerative mechanism of this scaffold is elaborated at the molecular level, which confirms that this strategy recreates a suitable immune microenvironment (anti‐inflammatory and M2‐polarizing) and drives functional cell and cytokine adhesion, as well as inchoate vascularization. It greatly enhances endogenous stem cell recruitment, and subsequently initiates robust vasculogenesis and osteogenesis. Significant bony reconstitution in the rabbit cranial defect model (Φ = 10 mm) is observed after 12 weeks, which realizes completely new bone coverage and 79% breaking load strength relative to the natural cranium. By enhancing nano‐sized functional interfacial integration, this strategy can provide effective guidance for developing highly bioactive bone‐regenerative implants.

Game analysis on regenerative synergy mechanism of the supply chain of integrate infrastructure engineering.

How to ensure the smooth implementation of convergent infrastructure engineering as the risk of sudden public events persists, allowing the engineering supply chain companies to break through the blockages to regenerate collaboratively and form a regenerated collaborative union. By establishing a mathematical game model, this paper explores the synergistic mechanism of supply chain regeneration for convergent infrastructure engineering, which takes into account cooperation and competition, investigates the impact of supply chain nodes' regeneration capacity and economic performance, as well as the dynamic changes in the importance weights of supply chain nodes, when adopting the collaborative decision of supply chain regeneration, the benefits of the supply chain system, are more than those when suppliers and manufacturers "act of one's own free will" by making decentralized decisions to undertake supply chain regeneration separately. All the investment costs of supply chain regeneration are higher than those in non-cooperative games. Based on the comparison of equilibrium solutions, it was found that exploring the collaborative mechanism of its convergence infrastructure engineering supply chain regeneration provides useful arguments for the emergency re-engineering of the engineering supply chain with a tube mathematical basis. Through constructing a dynamic game model for the exploration of the supply chain regeneration synergy mechanism, this paper provides methods and support for the emergency synergy among subjects of infrastructure construction projects, especially in improving the mobilization effectiveness of the entire infrastructure construction supply chain in critical emergencies and enhancing the emergency re-engineering capability of the supply chain.

The resurrection of earlier imprints post mortem: Explaining the Turkish agricultural cooperative movement with an imprinting theory lens, 1888–1937

AbstractThis study aims to extend the cooperative lifecycle theory, which builds on consecutive degeneration and regeneration of ideal cooperative values such as democracy, self‐help, and solidarity by offering a new regenerative mechanism. In this respect, the study imports multilevel imprinting theory from the organizational ecology domain to explicate the punctuated evolutionary pattern of Turkish agricultural credit cooperatives, which displayed significantly different characteristics from Raiffeisen cooperatives that cooperative discourse in Türkiye used for a long as a benchmark. The archival research undertaken in the study asserts that the imprints of Ottoman Memleket Sandiks (OMS) have stamped agricultural credit cooperatives of the Republican era long after their erosion. The resurrection of imprints was enabled by Ziraat Bank, which acted as an intermediary organization and took over the remnants of OMSs. Our analyses also suggest that the State's polity and policy transformations culminate in selective activation of past imprints within the Ziraat Bank, which, in turn, shaped the Turkish agricultural cooperative field.

State of the art on challenges for friction material manufacturers – raw materials, regulations, environmental, and NVH aspects

Friction materials have played a crucial role in safe movement of automobiles and in protection of human life. Enormous cost has incurred in validation of new developed brake pad, a critical safety component, as it involves a lot of inhouse testing along with field testing in different terrains. Further, with an unexpected pandemic and wars, creeping raw material price increases which is a major issue even though researchers have tried to develop innovative materials, which can perform multitasks. Moreover, a paradigm shift towards hybrid and electric vehicles required adjustments in design strategies, related to new friction materials for brakes. The regenerative braking mechanism has taken a major role in electric vehicles (EVs). Therefore, the friction pad is rarely used, which leads to rust/corrosion issues. In addition, the exhaust particles now pale in comparison to non-exhaust emissions. It is a newly identified challenge faced by friction industry as the brake pad wear is one of main contributors of non-exhaust emissions. Also, with no engine noise to cover, the silent nature of EVs creates noise and vibration issues in brake pad even more apparent. Hence, this paper has focused critically on challenges for friction material manufacturers in terms of regulations and raw materials followed by environmental issues and shift towards EVs and NVH requirement. Further, it has discussed with some possible suggestions to reduce the same.

Nonlinear dynamics of friction-induced regenerative chatter in internal turning with process damping forces

Stability in internal turning operation depends on several factors such as cutting conditions, tool overhang, associated tool dynamics, regeneration, friction and process damping. In the present work, an improved friction-induced regenerative chatter mechanism is introduced for internal turning operations with the help of a two-degree of freedom (DOF) cutting tool model by considering structural nonlinearities and process damping effects. The model is initially validated with the existing linear stability analysis theory via the natural parameter continuation method. The stability lobes obtained from the proposed model predict the stable regions with good accuracy. Furthermore, the nonlinear behaviour of the cutting tool with Stribeck and regenerative effects under internal resonance and primary resonance conditions is investigated. The nonlinear dynamic responses and the cutting stability are predicted using the higher-order method of multiple time scales (MMTS). The effect of nonlinearities on the frequency response and stability is studied in detail and the system parameters for stable cutting operations are identified. In order to validate the cutting states of the stability diagrams, internal turning experiments are performed on AISI 1020 carbon steel workpieces and the stability conditions are found to be in good agreement.

Super‐Fast and Super‐Long‐Life Rechargeable Zinc Battery

AbstractDespite their low cost, safety, environmentally friendliness, and intrinsic non‐flammable nature, the widespread application of aqueous rechargeable zinc‐based batteries has been held back by their low coulombic efficiency and the notorious dendritic growth at the zinc‐based anodes, along with the fast capacity fading of the cathodes. Herein, an aqueous Zn superbattery that consists of a mixed ZnCO3 MnCO3 grafted onto a graphene aerogel (ZMG) negative electrode and a nanotubular sulfidated NiCoFe layered double hydroxide (LDHS) positive electrode is reported. The alkaline ZMG││LDHS superbattery delivers an excellent capacity and a superb rate capability (356 mA h g−1cathode (89 mA h g−1total mass) at 12 A g−1; 108 mA h g−1cathode at 300 A g−1), extremely high specific energy and power (568 W h kg−1cathode or 15.8 mW h cm−3, 429 kW kg−1cathode or 11.9 W cm−3), along with a high output voltage (1.8 V). The device also exhibits unprecedented cycling stability (99.2% capacity retention after 17,000 cycles at 100% depth of discharge) thanks to an electrochemical pulse‐driven regenerative mechanism.

Physiology-Inspired Multilayer Nanofibrous Membranes Modulating Endogenous Stem Cell Recruitment and Osteo-Differentiation for Staged Bone Regeneration.

Bone regeneration involves a cascade of sophisticated, multiple-staged cellular and molecular events, where early-phase stem cell recruitment mediated by chemokines and late-phase osteo-differentiation induced by pro-osteogenic factors play the crucial roles. Herein, enlightened by a bone physiological and regenerative mechanism, the multilayer nanofibrous membranes (PLLA@SDF-1α@MT01) consisting of PLLA/MT01 micro-sol electrospun nanofibers as intima and PLLA/PEG/SDF-1α electrospun nanofibers as adventitia are fabricated through micro-sol electrospinning and manual multi-layer stacking technologies. In vitro releasing profiles show that PLLA@SDF-1α@MT01 represents the rapid release of stromal cell-derived SDF-1α(SDF-1α) in the outer layers, while with long-term sustained release of MT01 in the inner layer. Owing to interconnected porosity like the natural bone extracellular matrix and improved hydrophilia, PLLA@SDF-1α@MT01 manifests good biocompatibility both in vitro and in vivo. Furthermore, PLLA@SDF-1α@MT01 can promote bone marrow mesenchymal stem cells (BMSCs) migration by amplifying the SDF-1α/CXCR4 axis and stimulating BMSCs osteo-differentiation via activating the MAPK pathway in vitro. PLLA@SDF-1α@MT01, with a programmed dual-delivery system, exhibits the synergetic promotion of bone regeneration and vascularization by emulating key characteristics of the staged bone repair in vivo. Overall, PLLA@SDF-1α@MT01 that mimics the endogenous cascades of bone regeneration can enrich the physiology-mimetic staged regenerative strategy and represent a promising tissue-engineered scaffold for the bone defect.