Engineering biomimetic scaffolds for bone regeneration: Chitosan/alginate/polyvinyl alcohol-based double-network hydrogels with carbon nanomaterials.

In this study, new types of hybrid double-network (DN) hydrogels composed of polyvinyl alcohol (PVA), chitosan (CH), and sodium alginate (SA) are introduced, with the hypothesis that this combination and incorporating multi-walled carbon nanotubes (MWCNTs) and graphene nanoplatelets (GNPs) will enhance osteogenetic differentiation and the structural and mechanical properties of scaffolds for bone tissue engineering applications. Initially, the impact of varying mass ratios of the PVA/CH/SA mixture on mechanical properties, swelling ratio, and degradability was examined. Based on this investigation, a mass ratio of 4:6:6 was determined to be optimal. At this ratio, the hydrogel demonstrated a Young's modulus of 47.5 ± 5 kPa, a swelling ratio of 680 ± 6 % after 3 h, and a degradation rate of 46.5 ± 5 % after 40 days. In the next phase, following the determination of the optimal mass ratio, CNTs and GNPs were incorporated into the 4:6:6 composite resulting in a significant enhancement in the electrical conductivity and stiffness of the scaffolds. The introduction of CNTs led to a notable increase of 36 % in the viability of MG63 osteoblast cells. Additionally, the inhibition zone test revealed that GNPs and CNTs increased the diameter of the inhibition zone by 49.6 % and 52.6 %, respectively.

Homotypic cell membrane-camouflaged biomimetic PLGA nanoparticle loading triptolide for the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated death worldwide. Beside early detection, early diagnosis, and early surgery, it is urgent to try new strategies for the treatment of HCC. Triptolide (TPL) has been employed to treat HCC. However, its clinical applications were restricted by the narrow therapeutic window, severe toxicity, and poor water-solubility. In this study, we developed cancer cell membrane-camouflaged biomimetic PLGA nanoparticles loading TPL (TPL@mPLGA) with the homologous targeting property for the treatment of HCC. The TPL@mPLGA was successfully prepared with particle size of 195.5 ± 7.5 nm and zeta potential at -21.5 ± 0.2 mV with good stability. The drug loading (DL) of TPL@mPLGA was 2.94%. After Huh-7 cell membrane coating, the natural Huh-7 cell membrane proteins were found to be retained on TPL@mPLGA, thus endowing the TPL@mPLGA with enhanced accumulation at tumor site, and better anti-tumor activity in vitro and in vivo when compared with TPL or TPL@PLGA. The TPL@mPLGA showed enhanced anti-tumor effects and reduced toxicity of TPL, which could be adopted for the treatment of HCC.

Advances in cell membrane-based biomimetic nanodelivery systems for natural products.

Active components of natural products, which include paclitaxel, curcumin, gambogic acid, resveratrol, triptolide and celastrol, have promising anti-inflammatory, antitumor, anti-oxidant, and other pharmacological activities. However, their clinical application is limited due to low solubility, instability, low bioavailability, rapid metabolism, short half-life, and strong off-target toxicity. To overcome these drawbacks, cell membrane-based biomimetic nanosystems have emerged that avoid clearance by the immune system, enhance targeting, and prolong drug circulation, while also improving drug solubility and bioavailability, enhancing drug efficacy, and reducing side effects. This review summarizes recent advances in the preparation and coating of cell membrane-coated biomimetic nanosystems and in their applications to disease for targeted natural products delivery. Current challenges, limitations, and prospects in this field are also discussed, providing a research basis for the development of multifunctional biomimetic nanosystems for natural products.

Biomimetic piezoelectric nanomaterial-modified oral microrobots for targeted catalytic and immunotherapy of colorectal cancer.

Lactic acid (LA) accumulation in the tumor microenvironment poses notable challenges to effective tumor immunotherapy. Here, an intelligent tumor treatment microrobot based on the unique physiological structure and metabolic characteristics of Veillonella atypica (VA) is proposed by loading Staphylococcus aureus cell membrane-coating BaTiO3 nanocubes (SAM@BTO) on the surface of VA cells (VA-SAM@BTO) via click chemical reaction. Following oral administration, VA-SAM@BTO accurately targeted orthotopic colorectal cancer through inflammatory targeting of SAM and hypoxic targeting of VA. Under in vitro ultrasonic stimulation, BTO catalyzed two reduction reactions (O2 → •O2- and CO2 → CO) and three oxidation reactions (H2O → •OH, GSH → GSSG, and LA → PA) simultaneously, effectively inducing immunogenic death of tumor cells. BTO catalyzed the oxidative coupling of VA cells metabolized LA, effectively disrupting the immunosuppressive microenvironment, improving dendritic cell maturation and macrophage M1 polarization, and increasing effector T cell proportions while decreasing regulatory T cell numbers, which facilitates synergetic catalysis and immunotherapy.

Spatially confined CuFe2O4 nanosphere in N/O-codoped porous carbon mimetics for triple-mode sensing of antibiotics and visual detection of neurotransmitters in biofluids.

BACKGROUND: Carbon-based nanozymes have recently received enormous concern, however, there is still a huge challenge for inexpensive and large-scale synthesis of magnetic carbon-based "Two-in-One" mimics with both peroxidase (POD)-like and laccase-like activities, especially their potential applications in multi-mode sensing of antibiotics and neurotransmitters in biofluids. Although some progresses have been made in this field, the feasibility of biomass-derived carbon materials with both POD-like and laccase-like activities by polyatomic doping strategy is still unclear. In addition, multi-mode sensing platform can provide a more reliable result because of the self-validation, self-correction and mutual agreement. Nevertheless, the use of magnetic carbon-based nanozyme sensors for the multi-mode detection of antibiotics and neurotransmitters have not been investigated. RESULTS: We herein report a shrimp shell-derived N, O-codoped porous carbon confined magnetic CuFe2O4 nanosphere with outstanding laccase-like and POD-like activities for triple-mode sensing of antibiotic d-penicillamine (D-PA) and chloramphenicol (CPL), as well as colorimetric detection of neurotransmitters in biofluids. The magnetic CuFe2O4/N, O-codoped porous carbon (MCNPC) armored mimetics was successfully fabricated using a combined in-situ coordination and high-temperature crystallization method. The synthesized MCNPC composite with superior POD-like activity can be used for colorimetric/temperature/smartphone-based triple-mode detection of D-PA and CPL in goat serum. Importantly, the MCNPC nanozyme can also be used for colorimetric analysis of dopamine and epinephrine in human urine. SIGNIFICANCE: This work not only offered a novel strategy to large-scale, cheap synthesize magnetic carbon-based "Two-in-One" armored mimetics, but also established the highly sensitive and selective platforms for triple-mode monitoring D-PA and CPL, as well as colorimetric analysis of neurotransmitters in biofluids without any tanglesome sample pretreatment.

Biominerals and Bioinspired Materials in Biosensing: Recent Advancements and Applications.

Inspired by nature's remarkable ability to form intricate minerals, researchers have unlocked transformative strategies for creating next-generation biosensors with exceptional sensitivity, selectivity, and biocompatibility. By mimicking how organisms orchestrate mineral growth, biomimetic and bioinspired materials are significantly impacting biosensor design. Engineered bioinspired materials offer distinct advantages over their natural counterparts, boasting superior tunability, precise controllability, and the ability to integrate specific functionalities for enhanced sensing capabilities. This remarkable versatility enables the construction of various biosensing platforms, including optical sensors, electrochemical sensors, magnetic biosensors, and nucleic acid detection platforms, for diverse applications. Additionally, bioinspired materials facilitate the development of smartphone-assisted biosensing platforms, offering user-friendly and portable diagnostic tools for point-of-care applications. This review comprehensively explores the utilization of naturally occurring and engineered biominerals and materials for diverse biosensing applications. We highlight the fabrication and design strategies that tailor their functionalities to address specific biosensing needs. This in-depth exploration underscores the transformative potential of biominerals and materials in revolutionizing biosensing, paving the way for advancements in healthcare, environmental monitoring, and other critical fields.

Biomimetic gradient scaffolds for the tissue engineering and regeneration of rotator cuff enthesis.

Rotator cuff tear is one of the most common musculoskeletal disorders, which often results in recurrent shoulder pain and limited movement. Enthesis is a structurally complex and functionally critical interface connecting tendon and bone that plays an essential role in maintaining integrity of the shoulder joint. Despite the availability of advanced surgical procedures for rotator cuff repair, there is a high rate of failure following surgery due to suboptimal enthesis healing and regeneration. Novel strategies based on tissue engineering are gaining popularity in improving tendon-bone interface (TBI) regeneration. Through incorporating physical and biochemical cues into scaffold design which mimics the structure and composition of native enthesis is advantageous to guide specific differentiation of seeding cells and facilitate the formation of functional tissues. In this review, we summarize the current state of research in enthesis tissue engineering highlighting the development and application of biomimetic scaffolds that replicate the gradient TBI. We also discuss the latest techniques for fabricating potential translatable scaffolds such as 3D bioprinting and microfluidic device. While preclinical studies have demonstrated encouraging results of biomimetic gradient scaffolds, the translation of these findings into clinical applications necessitates a comprehensive understanding of their safety and long-term efficacy.

Antiviral Activities of Heparan Sulfate Mimetic RAFT Polymers Against Mosquito-borne Viruses.

Mosquito-borne viruses are a major worldwide health problem associated with high morbidity and mortality rates and significant impacts on national healthcare budgets. The development of antiviral drugs for both the treatment and prophylaxis of these diseases is thus of considerable importance. To address the need for therapeutics with antiviral activity, a library of heparan sulfate mimetic polymers was screened against dengue virus (DENV), Yellow fever virus (YFV), Zika virus (ZIKV), and Ross River virus (RRV). The polymers were prepared by RAFT polymerization of various acidic monomers with a target MW of 20 kDa (average Mn ∼ 27 kDa by GPC). Among the polymers, poly(SS), a homopolymer of sodium styrenesulfonate, was identified as a broad spectrum antiviral with activity against all the tested viruses and particularly potent inhibition of YFV (IC50 = 310 pM). Our results further uncovered that poly(SS) exhibited a robust inhibition of ZIKV infection in both mosquito and human cell lines, which points out the potential functions of poly(SS) in preventing mosquito-borne viruses associated diseases by blocking viral transmission in their mosquito vectors and mitigating viral infection in patients.

Photocatalytic regeneration of nicotinamide cofactor biomimetics drives biocatalytic reduction by Old Yellow enzymes.

A key approach in developing green chemistry involves converting solar energy into chemical energy of biomolecules through photocatalysis. Photocatalysis can facilitate the regeneration of nicotinamide cofactors during redox processes. Nicotinamide cofactor biomimetics (NCBs) are economical substitutes for natural cofactors. Here, photocatalytic regeneration of NADH and reduced NCBs (NCBsred) using graphitic carbon nitride (g-C3N4) was developed. The process involves g-C3N4 as the photocatalyst, Cp*Rh(bpy)H2O2+ as the electron mediator, and Triethanolamine as the electron donor, facilitating the reduction of NAD+ and various oxidative NCBs (NCBsox) under light irradiation. Notably, the highest reduction yield of 48.32 % was achieved with BANA+, outperforming the natural cofactor NAD+. Electrochemical analysis reveals that the reduction efficiency and capacity of cofactors relies on their redox potentials. Additionally, a coupled photo-enzymatic catalysis system was explored for the reduction of 4-Ketoisophorone by Old Yellow Enzyme XenA. Among all the NCBsox and NAD+, the highest conversion ratio of over 99 % was obtained with BANA+. After recycled for 8 times, g-C3N4 maintained over 93.6 % catalytic efficiency. The photocatalytic cofactor regeneration showcases its outstanding performance with NAD+ as well as NCBsox. This work significantly advances the development of photocatalytic cofactor regeneration for artificial cofactors and its potential application.

Nested structure role in the mechanical response of spicule inspired fibers.

Euplectella aspergillummarine sponge spicules are renowned for their remarkable strength and toughness. These spicules exhibit a unique concentric layering structure, which contributes to their exceptional mechanical resistance. In this study, finite element method simulations were used to comprehensively investigate the effect of nested cylindrical structures on the mechanical properties of spicules. This investigation leveraged scanning electron microscopy images to guide the computational modeling of the microstructure and the results were validated by three-point bending tests of 3D-printed spicule-inspired structures. The numerical analyses showed that the nested structure of spicules induces stress and strain jumps on the layer interfaces, reducing the load on critical zones of the fiber and increasing its toughness. It was found that this effect shows a tapering enhancement as the number of layers increases, which combines with a threshold related to the 3D-printing manufacturability to suggest a compromise for optimal performance. A comprehensive evaluation of the mechanical properties of these fibers can assist in developing a new generation of bioinspired structures with practical real-world applications.

A bimetallic peroxidase-mimicking nanozyme with antifouling property for construction of sensor array to identify phosphoproteins and diagnose cancers.

Protein phosphorylation is a significant post-translational modification that plays a decisive role in the occurrence and development of diseases. However, the rapid and accurate identification of phosphoproteins remains challenging. Herein, a high-throughput sensor array has been constructed based on a magnetic bimetallic nanozyme (Fe3O4@ZNP@UiO-66) for the identification and discrimination of phosphoproteins. Attributing to the formation of Fe-Zr bimetallic dual active centers, the as-prepared Fe3O4@ZNP@UiO-66 exhibits enhanced peroxidase-mimicking catalytic activity, which promotes the electron transfer from Zr center to Fe(II)/Fe(III). The catalytic activity of Fe3O4@ZNP@UiO-66 can be selectively inhibited by phosphoproteins due to the strong interaction between phosphate groups and Zr centers, as well as the ultra-robust antifouling capability of zwitterionic dopamine nanoparticle (ZNP). Considering the diverse binding affinities between various proteins with the nanozyme, the catalytic activity of Fe3O4@ZNP@UiO-66 can be changed to various degree, leading to the different absorption responses at 420 nm in the hydrogen peroxide (H2O2) - 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) system. By simply extracting different absorbance intensities at various time points, a sensor array based on reaction kinetics for the discrimination of phosphoproteins from other proteins is constructed through linear discriminant analysis (LDA). Besides, the quantitative determination of phosphoproteins and identification of protein mixtures have been realized. Further, based on the differential level of phosphoproteins in cells, the differentiation of cancer cells from normal cells can also be implemented by utilizing the proposed sensor array, showing great potential in disease diagnosis.

High-density lipoprotein mimetic nano-therapeutics targeting monocytes and macrophages for improved cardiovascular care: a comprehensive review.

The prevalence of cardiovascular diseases continues to be a challenge for global health, necessitating innovative solutions. The potential of high-density lipoprotein (HDL) mimetic nanotherapeutics in the context of cardiovascular disease and the intricate mechanisms underlying the interactions between monocyte-derived cells and HDL mimetic showing their impact on inflammation, cellular lipid metabolism, and the progression of atherosclerotic plaque. Preclinical studies have demonstrated that HDL mimetic nanotherapeutics can regulate monocyte recruitment and macrophage polarization towards an anti-inflammatory phenotype, suggesting their potential to impede the progression of atherosclerosis. The challenges and opportunities associated with the clinical application of HDL mimetic nanotherapeutics, emphasize the need for additional research to gain a better understanding of the precise molecular pathways and long-term effects of these nanotherapeutics on monocytes and macrophages to maximize their therapeutic efficacy. Furthermore, the use of nanotechnology in the treatment of cardiovascular diseases highlights the potential of nanoparticles for targeted treatments. Moreover, the concept of theranostics combines therapy and diagnosis to create a selective platform for the conversion of traditional therapeutic medications into specialized and customized treatments. The multifaceted contributions of HDL to cardiovascular and metabolic health via highlight its potential to improve plaque stability and avert atherosclerosis-related problems. There is a need for further research to maximize the therapeutic efficacy of HDL mimetic nanotherapeutics and to develop targeted treatment approaches to prevent atherosclerosis. This review provides a comprehensive overview of the potential of nanotherapeutics in the treatment of cardiovascular diseases, emphasizing the need for innovative solutions to address the challenges posed by cardiovascular diseases.

Application and advances of biomimetic membrane materials in central nervous system disorders.

Central nervous system (CNS) diseases encompass spinal cord injuries, brain tumors, neurodegenerative diseases, and ischemic strokes. Recently, there has been a growing global recognition of CNS disorders as a leading cause of disability and death in humans and the second most common cause of death worldwide. The global burdens and treatment challenges posed by CNS disorders are particularly significant in the context of a rapidly expanding global population and aging demographics. The blood-brain barrier (BBB) presents a challenge for effective drug delivery in CNS disorders, as conventional drugs often have limited penetration into the brain. Advances in biomimetic membrane nanomaterials technology have shown promise in enhancing drug delivery for various CNS disorders, leveraging properties such as natural biological surfaces, high biocompatibility and biosafety. This review discusses recent developments in biomimetic membrane materials, summarizes the types and preparation methods of these materials, analyzes their applications in treating CNS injuries, and provides insights into the future prospects and limitations of biomimetic membrane materials.

Ti3C2 Nanosheets Functionalized with Ferritin-Biomimetic Platinum Nanoparticles for Electrochemical Biosensors of Nitrite.

Nitrites widely exist in human life and the natural environment, but excessive contents of nitrites will result in adverse effects on the environment and human health; hence, sensitive and stable nitrite detection systems are needed. In this study, we report the synthesis of Ti3C2 nanosheets functionalized with apoferritin (ApoF)-biomimetic platinum (Pt) nanoparticle (Pt@ApoF/Ti3C2) composite materials, which were formed by using ApoF as a template and protein-inspired biomineralization. The formed nanohybrid exhibits excellent electrochemical sensing performance towards nitrite (NaNO2). Specifically, the Pt@ApoF catalyzes the conversion of nitrites into nitrates, converting the chemical signal into an electrical signal. The prepared Pt@ApoF/Ti3C2-based electrochemical NaNO2 biosensors demonstrate a wide detection range of 0.001-9 mM with a low detection limit of 0.425 µM. Additionally, the biosensors possess high selectivity and sensitivity while maintaining a relatively stable electrochemical sensing performance within 7 days, enabling the monitoring of NaNO2 in complex environments. The successful preparation of the Pt@ApoF/Ti3C2 nanohybrid materials provides a new approach for constructing efficient electrochemical biosensors, offering a simple and rapid method for detecting NaNO2 in complex environments.

Gradients of properties increase the morphing and stiffening performance of bioinspired synthetic fin rays.

State-of-the-art morphing materials are either very compliant to achieve large shape changes (flexible metamaterials, compliant mechanisms, hydrogels), or very stiff but with infinitesimal changes in shape that require large actuation forces (metallic or composite panels with piezoelectric actuation). Morphing efficiency and structural stiffness are therefore mutually exclusive properties in current engineering morphing materials, which limits the range of their applicability. Interestingly, natural fish fins do not contain muscles, yet they can morph to large amplitudes with minimal muscular actuation forces from the base while producing large hydrodynamic forces without collapsing. This sophisticated mechanical response has already inspired several synthetic fin rays with various applications. However, most 'synthetic' fin rays have only considered uniform properties and structures along the rays while in natural fin rays, gradients of properties are prominent. In this study, we designed, modeled, fabricated and tested synthetic fin rays with bioinspired gradients of properties. The rays were composed of two hemitrichs made of a stiff polymer, joined by a much softer core region made of elastomeric ligaments. Using combinations of experiments and nonlinear mechanical models, we found that gradients in both the core region and hemitrichs can increase the morphing and stiffening response of individual rays. Introducing a positive gradient of ligament density in the core region (the density of ligament increases towards the tip of the ray) decreased the actuation force required for morphing and increased overall flexural stiffness. Introducing a gradient of property in the hemitrichs, by tapering them, produced morphing deformations that were distributed over long distances along the length of the ray. These new insights on the interplay between material architecture and properties in nonlinear regimes of deformation can improve the designs of morphing structures that combine high morphing efficiency and high stiffness from external forces, with potential applications in aerospace or robotics.

Acid-Activated TAT Peptide-Modified Biomimetic Boron Nitride Nanoparticles for Enhanced Targeted Codelivery of Doxorubicin and Indocyanine Green: A Synergistic Cancer Photothermal and Chemotherapeutic Approach.

The evolution of nano-drug delivery systems addresses the limitations of conventional cancer treatments with stimulus-responsive nanomaterial-based delivery systems presenting temporal and spatial advantages. Among various nanomaterials, boron nitride nanoparticles (BNNs) demonstrate significant potential in drug delivery and cancer treatment, providing a high drug loading capacity, multifunctionality, and low toxicity. However, the challenge lies in augmenting nanomaterial accumulation exclusively within tumors while preserving healthy tissues. To address this, we introduce a novel approach involving cancer cell membrane-functionalized BNNs (CM-BIDdT) for the codelivery of doxorubicin (Dox) and indocyanine green to treat homologous tumor. The cancer cell membrane biomimetic CM-BIDdT nanoparticles possess highly efficient homologous targeting capabilities toward tumor cells. The surface modification with acylated TAT peptides (dTAT) further enhances the nanoparticle intracellular accumulation. Consequently, CM-BIDdT nanoparticles, responsive to the acidic tumor microenvironment, hydrolyze amide bonds, activate the transmembrane penetrating function, and achieve precise targeting with substantial accumulation at the tumor site. Additionally, the photothermal effect of CM-BIDdT under laser irradiation not only kills cells through thermal ablation but also destroys the membrane on the surface of the nanoparticles, facilitating Dox release. Therefore, the fabricated CM-BIDdT nanoparticles orchestrate chemo-photothermal combination therapy and effectively inhibit tumor growth with minimal adverse effects, holding promise as a new modality for synergistic cancer treatment.

Avian eye-inspired perovskite artificial vision system for foveated and multispectral imaging.

Avian eyes have deep central foveae as a result of extensive evolution. Deep foveae efficiently refract incident light, creating a magnified image of the target object and making it easier to track object motion. These features are essential for detecting and tracking remote objects in dynamic environments. Furthermore, avian eyes respond to a wide spectrum of light, including visible and ultraviolet light, allowing them to efficiently distinguish the target object from complex backgrounds. Despite notable advances in artificial vision systems that mimic animal vision, the exceptional object detection and targeting capabilities of avian eyes via foveated and multispectral imaging remain underexplored. Here, we present an artificial vision system that capitalizes on these aspects of avian vision. We introduce an artificial fovea and vertically stacked perovskite photodetector arrays whose designs were optimized by theoretical simulations for the demonstration of foveated and multispectral imaging. The artificial vision system successfully identifies colored and mixed-color objects and detects remote objects through foveated imaging. The potential for use in uncrewed aerial vehicles that need to detect, track, and recognize distant targets in dynamic environments is also discussed. Our avian eye-inspired perovskite artificial vision system marks a notable advance in bioinspired artificial visions.

A biomimetic ion channel shortens the QT interval of type 2 long QT syndrome through efficient transmembrane transport of potassium ions.

Potassium ion transport across myocardial cell membrane is essential for type 2 long QT syndrome (LQT2). However, the dysfunction of potassium ion transport due to genetic mutations limits the therapeutic effect in treating LQT2. Biomimetic ion channels that selectively and efficiently transport potassium ions across the cellular membranes are promising for the treatment of LQT2. To corroborate this, we synthesized a series of foldamer-based ion channels with different side chains, and found a biomimetic ion channel of K+ (BICK) with the highest transport activity among them. The selected BICK can restore potassium ion transport and increase transmembrane potassium ion current, thus shortening phase 3 of action potential (AP) repolarization and QT interval in LQT2. Moreover, BICK does not affect heart rate and cardiac rhythm in treating LQT2 model induced by E4031 in isolated heart as well as in guinea pigs. By restoring ion transmembrane transport tactic, biomimetic ion channels, such as BICK, will show great potential in treating diseases related to ion transport blockade. STATEMENT OF SIGNIFICANCE: Type 2 long QT syndrome (LQT2) is a disease caused by K+ transport disorder, which can cause malignant arrhythmia and even death. There is currently no radical cure, so it is critical to explore ways to improve K+ transmembrane transport. In this study, we report that a small-molecule biomimetic ion channel BICK can efficiently simulate natural K+ channel proteins on the cardiomyocyte and cure E4031-induced LQT2 in guinea pig by restoring K+ transport function for the first time. This study found that the potassium transmembrane transport by BICK significantly reduced the QT interval, which provides a conceptually new strategy for the treatment of LQT2 disease.

Avian eye-inspired artificial vision takes a step forward.

Bioinspiration from avian eyes allows development of artificial vision systems with foveated and multispectral imaging.