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With specific and inherent mRNA cleaving activity, small interfering RNA against pro-fibrosis factor (PAI-1 siRNA, siPAI-1) has demonstrated the fucntion for preventing diminished ovarian reserve (DOR). Moreover, safe nanomaterials have provided ideal tools for delivering siRNA to the targeted cells to obtain high therapeutic efficacy. In order to improve the preventing capability of siPAI-1 for DOR, we synthesized one kind of biomimetic Poly (lactic-co-glycolic acid) copolymer (PLGA)-based nanoparticles (siPAI-1@PLGA@M-FSHL, abbreviated as SPMF). siPAI-1 was assembled into cationic PLGA nanoparticles, following with macrophage membrane coating (M) and FSHL81-95 peptide modification. SPMF NPs significantly enhanced cellular uptake and gene silencing efficiency in KGN cells in vitro. In vivo assay demonstrated that SPMF NPs can targetedly accumulate in the ovarian of DOR mice with Cyclophosphamide treatment (80 mg/kg/week, 2 weeks) and remarkably downregulate the levels of PAI-1 in ovarian, which finally resulted in the effective suppression of ovary fibrosis and improved the chemotherapy-induced follicle loss to increase the number of primordial, secondary, antral follicles by 62.05 %, 54.92 % and 64.37 %, respectively, compared with DOR group. In summary, this study demonstrates that siPAI-1-loaded SPMF with high safety and efficacy can potentially alleviate DOR by inhibiting the overexpression of PAI-1 in the ovarian., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The main pathological mechanisms of Alzheimer's Disease (AD) are extracellular senile plaques caused by β-amyloid (Aβ) deposition and intracellular neurofibrillary tangles derived from hyperphosphorylated Tau protein (p-Tau). However, it is difficult to obtain a good curative effect because of the poor brain bioavailability of drugs, which is attributed to the blood-brain barrier (BBB) restriction and complicated brain conditions. Herein, HM-DK was proposed for synergistic therapy of AD by using hollow mesoporous manganese dioxide (HM) as a carrier to deliver an Aβ-inhibiting peptide and a Dp-peptide inhibitor of Tau-related fibril formation synergistically. Inspired by 4T1 cancer cells promoting BBB penetration during brain metastasis, a prospective biomimetic nanocarrier (HM-DK@CM) encapsulated by 4T1 cell membranes was designed. After crossing the BBB, HM-DK@CM inhibited Aβ aggregation and prevented Tau phosphorylation simultaneously. Moreover, by taking advantage of the catalase-like activity of HM, HM-DK@CM relieved oxidative stress and altered the microenvironment associated with the development of AD. Compared with the single therapeutic drug, HM-DK@CM restored nerve damage and improved AD mice's learning and memory abilities by decreasing Aβ oligomer, p-Tau protein, and inflammation through various pathways for synergistic therapy, which has broad prospects for the effective treatment of AD.

Bacterial pneumonia has garnered significant attention in the realm of infectious diseases owing to a surge in the incidence of severe infections coupled with the growing scarcity of efficacious therapeutic modalities. Antibiotic treatment is still an irreplaceable method for bacterial pneumonia because of its strong bactericidal activity and good clinical efficacy. However, the mucus layer forming after a bacterial infection in the lungs has been considered as the "Achilles' heels" facing the clinical application of such treatment. Herein, traceable biomimetic nanoantibiotics (BioNanoCFPs) were developed by loading indacenodithieno[3,2- b ]thiophene (ITIC) and cefoperazone (CFP) in nanoplatforms coated with natural killer (NK) cell membranes. The BioNanoCFP exhibited excellent demonstrated mucus-penetrating abilities, facilitating their arrival at the infection site. The presence of Toll-like receptors in the NK cell membrane rendered the BioNanoCFP with the capability to recognize pathogen-associated molecular patterns within bacteria, allowing precise targeting of bacterial colonization sites and achieving substantial therapeutic efficacy. Overall, our findings demonstrate the viability and desirability of using NK cell membrane-mediated drug delivery as a promising strategy for precision treatment.

The chemoresistance and systemic toxicity of cisplatin (CDDP) severely limit its application in the treatment of non-small cell lung cancer (NSCLC). Here, I-124 labeled cancer cell membrane biomimetic nanovesicles loading Polyphyllin VI (PPVI) and CDDP (termed 124 I-P/C@CMLvs) were constructed to enhance the sensitivity and efficacy of CDDP. The radiochemical purity (RCP) of 124 I-P/C@CMLvs reached more than 99% and maintained reliable stability in vitro. Micro-positron emission tomography (micro-PET) imaging of I-124 quantitatively revealed the distribution and specific homologous tumor targeting ability of 124 I-P/C@CMLvs in vivo with superior diagnosis performance, beneficial for dynamically monitoring the efficacy against NSCLC. Loaded PPVI significantly strengthened the sensitivity of NSCLC to CDDP therapy and exerted synergistic anti-tumor effect in vitro and in vivo, which was achieved by PPVI promoting p53 deubiquitination and stimulating reactive oxygen species (ROS) production to trigger the crosstalk between the amplification of GPX4 signaling-mediated ferroptosis and NLRP3/GSDMD/Caspase-1 axis-mediated pyroptosis. 124 I-P/C@CMLvs also significantly stimulated the infiltration of immune cells including dendritic cells, CD8 + T cells, and CD4 + T cells in tumor tissues ( P < 0.05). The combination of 124 I-P/C@CMLvs and anti-PD-L1 therapy further synergistically promoted NSCLC regression. Altogether, 124 I-P/C@CMLvs provide a transformational solution to the challenge of improving CDDP sensitivity and realizing the integration of diagnosis, treatment, and monitoring of NSCLC.

Introduction: Biomineralization has been increasingly adopted for the synthesis of advanced materials with superior properties. Hierarchical architecture growth mimicking biomineralization has been studied using various organic molecules to template inorganic materials with controlled morphology. In our previous study, self-assembled Sr/CS/G(SrCO 3 -chitosan-gelatin) aggregates were fabricated using electrophoretic deposition (EPD). This study is a further step toward understanding the morphogenesis of Sr/CS/G aggregates and its biomineralization., Methods: Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD) were used to investigate the biomimetic morphogenesis of Sr/CS/G composite under various EPD parameters, such as polymer concentration, time, and voltage. The Sr/CS/G aggregates were immersed in H 2 O, phosphate-buffered saline (PBS), and simulated body fluid (SBF) to study the bioactive apatite formation ability. In addition, biocompatibility of the composites were evaluated by Fluorescence staining, SEM in vitro. The osteogenic ability of the coatings induced by PBS were tested in vivo., Results: The CS/G weight ratio, EPD time, and voltage were found to influence the morphogenesis of Sr/CS/G aggregates. SEM and TEM results showed that the Sr/CS/G aggregates exhibited fractal growth characteristics and morphological self-similarity. XRD results confirmed the formation of SrCO 3 crystals within the framework of chitosan and gelatin organic templates. Chitosan played a vital role in branching growth of the crystals, whereas gelatin guided the formation of composite spheres. The microstructural and compositional results reveal that the Sr/CS/G-induced apatite coating yielded a large quantity of apatite. These apatite coatings promote the cytocompatibility and osteogenesis of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. The coatings induced by PBS enhanced proliferation and mineralization in vitro, and enhanced angiogenesis and osteogenesis in vivo., Conclusion: Sr/CS/G composites prepared via EPD are promising organic-inorganic templates for biomineralization. These findings provide important insights into understanding the mineralization process and optimizing the design of advanced biological materials., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Gong et al.)

Optic nerve regeneration remains challenging worldwide due to the limited intrinsic regenerative capacity of retinal ganglion cells (RGCs) and the inhibitory microenvironment. Oxidative stress, induced by excessive reactive oxygen species (ROS) following optic nerve injury, is associated with prolonged neuroinflammation, resulting in a secondary injury of RGCs and the impairment of axon regeneration. Herein, we developed a bionic nanocomposite scaffold (GA@PDA) with immunoregulatory ability for enhanced optic nerve regeneration. The ice-templating method was employed to fabricate biopolymer-based scaffolds with a directional porous structure, mimicking the optic nerve, which effectively guided the oriented growth of neuronal cells. The incorporation of bioinspired polydopamine nanoparticles (PDA NPs) further confers excellent ROS scavenging ability, thereby modulating the phenotype transformation of microglia/macrophages from pro-inflammatory M1 to anti-inflammatory M2. In a rat optic nerve crush model, the implantation of GA@PDA scaffold enhanced survival of RGCs and promoted axonal regeneration. Our study offers novel insights and holds promising potential for the advancement of engineered biomaterials in facilitating optic nerve regeneration., (© 2024. The Author(s).)

Background: Cardiac microvascular damage is substantially related with the onset of myocardial ischaemia-reperfusion (IR) injury. Reportedly, allicin (AL) effectively protects the cardiac microvascular system from IR injury. However, the unsatisfactory therapeutic efficacy of current drugs and insufficient drug delivery to the damaged heart are major concerns. Here, inspired by the natural interaction between neutrophils and inflamed cardiac microvascular endothelial cells (CMECs), a neutrophil membrane-camouflaged nanoparticle for non-invasive active-targeting therapy for IR injury by improving drug delivery to the injured heart is constructed., Methods: In this study, we engineered mesoporous silica nanoparticles (MSNs) coated with a neutrophil membrane to act as a drug delivery system, encapsulating AL. The potential of the nanoparticles (named AL@MSNs@NM) for specific targeting of infarcted myocardium was assessed using small animal vivo imaging system. The cardiac function of AL@MSNs@NM after treatment was evaluated by Animal Ultrasound Imaging system, HE staining, and Laser Speckle Imaging System. The therapeutic mechanism was analyzed by ELISA kits, immunofluorescence, and PCR., Results: We discovered that AL@MSNs@NM significantly improves cardiac function index, reduced infarct size and fibrosis, increased vascular perfusion in ischemic areas, and also promoted the function of CMECs, including migration, tube formation, shear stress adaptation, and nitric oxide production. Further research revealed that AL@MSNs@NM have cardio-protective functions in IR rats by inhibiting CMEC ferroptosis and increasing platelet endothelial cell adhesion molecule-1 (PECAM-1) expression., Conclusion: Our results indicated that AL@MSNs@NM significantly reversed CMEC ferroptosis and increased PECAM-1 expression, enhanced cardiac function, and reduced myocardial infarction size. Therefore, this strategy demonstrates that engineered biomimetic nanotechnology effectively delivers AL for targeted therapy of myocardial infarction., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Li et al.)

The development and progression of tumors are characterized by intricate biological processes. Monotherapy not only struggles to achieve effective treatment but also tends to precipitate a series of issues, including multidrug resistance and limited antitumor effect. Consequently, it is imperative to adopt a synergistic multitherapy approach to enhance the efficacy of tumor treatment. The integration of chemotherapy drug with oligonucleotide drug for combinational treatment has shown significant promise in improving tumor therapeutic efficiency. However, the effective in vivo codelivery of oligonucleotide drugs and chemotherapy drugs faces substantial challenges such as poor stability of oligonucleotide drugs during the circulation time, limited tumor accumulation, and uncertain delivery ratios of different payloads. To overcome these obstacles, we have engineered cyclic Arg-Gly-Asp (cRGD)-modified red blood cell membrane (RBCm)-coated multidrug nanocomplexes, which were self-assembled from the Polo-like kinase 1 siRNA (siPlk1) and an irreversible tyrosine kinase inhibitor neratinib targeted to human epidermal growth factor receptor 2 (HER2) overexpressed in breast cancer. Through electrostatic and amphiphilic interactions between the positively charged neratinib and negatively charged siPlk1, we have successfully fabricated uniform multidrug nanoparticles. The cRGD-modified red blood cell membranes coated on the surface of the multidrug nanoparticles could enhance drug stability in circulation and tumor accumulation. This targeted combinational therapy significantly enhanced the antitumor efficiency in HER2-positive breast cancer in vitro and in vivo .

Rheumatoid arthritis (RA) is a chronic disease characterized by immune cell infiltration and cartilage damage. The local lesion of RA shows severe oxidative stress and proinflammatory cytokine secretion. For drug therapy, the efficacy of agents, such as methotrexate (MTX), may be greatly limited, resulting from the low bioavailability, immune clearance, and toxic side effects. A nanocarrier (TA-PBA NPs) was developed with anti-inflammatory and antioxidant activities, combined with MTX to prepare nanomedicine (MTX NPs) for synergistic treatment of RA. Moreover, inspired by the biological functions homing to inflammation lesion of macrophages, the biomimetic nanomedicine camouflaged with macrophage membrane (MM@MTX NPs) was constructed. TA-PBA NPs could timely promote MTX release in response to the overaccumulated ROS to exhibit high anti-inflammatory and antioxidant activities for alleviating RA progression. The experimental results confirmed that MM@MTX NPs could significantly reduce the secretion of proinflammatory cytokines (TNF-α) while significantly increasing the typical anti-inflammatory cytokines (IL-10), promote the phenotype transformation of macrophages from M1 to M2, and up-regulate the Nrf2-keap1 pathway-related proteins (HO-1 and NRF2) to positively regulate the local inflammation for effectively inhibiting RA development. Thus, MM@MTX NPs represent a possible candidate as a safe and efficient nanotherapy platform for RA management.

Chronic refractory wounds have become a serious threat to human health and are characterized by prolonged inflammation, recurrent bacterial infections, and elevated ROS levels. However, current therapeutic strategies usually target a unilateral healing function and are unable to tackle the complexity and sensitivity of chronic refractory wound healing. This study fabricated a biomimetic nanozyme based on rhein (Cu-rhein NSs), which effectively mimics the activity of superoxide dismutase (SOD) for scavenging various free radicals. Additionally, zinc oxide microspheres (ZnO MSs) were prepared to enhance the antibacterial activity and mechanical properties of the modified hydrogel. Cu-rhein NSs and ZnO MSs were comodified onto an extracellular matrix-mimetic dual-network smart hydrogel constructed from oxidized sodium alginate, gelatin, and borax via dynamic borate and Schiff base bonds. The smart hydrogel presented the good biocompatibility and targeted the unique acidic microenvironment with high oxidative stress of chronic refractory wounds, intelligently releasing bionic nanozymes to effectively eliminate bacteria, reduce inflammatory responses, and scavenge multiple free radicals for reducing ROS. In vivo experiments on the rat model based on diabetic infection showed that the smart hydrogel could effectively eliminate bacteria, promote vascular regeneration and collagen deposition, reduce inflammatory response, and accelerate the healing of diabetic-infected wounds (almost complete healing within 14 days). The advantages of an intelligent, biomimetic tissue regeneration cascade management strategy against diabetic infected wound healing are highlighted.

Thromboembolic stroke constitutes the majority of brain strokes, resulting in elevated mortality and morbidity rates, as well as significant societal and economic burdens. Although intravenous thrombolysis serves as the standard clinical treatment, its narrow therapeutic window and the inflammatory response induced by tissue plasminogen activator (tPA) administration limit its efficacy. In the initial stages of stroke, the abrupt cessation of blood flow leads to an energy metabolism disorder, marked by a substantial decrease in adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH) levels, causing irreversible damage to neural cells. In this study, we introduce a neutrophil-mimetic, microalgae-derived upconversion photosynthetic nanosystem designed for targeted treatment of thromboembolic stroke. This system features upconversion nanoparticles coated with a thylakoid membrane and wrapped in an activated neutrophil membrane, further decorated with ROS-responsive thrombolytic tPA on its surface. The neutrophil-mimetic design facilitates high targeting specificity and accumulation at the thrombus site after intravenous administration. Upon exposure to elevated levels of reactive oxygen species (ROS) at the thrombus location, the nanosystem promptly demonstrated potent thrombolytic efficacy through the surface-modified tPA. Furthermore, near-infrared II (NIR-II) laser irradiation activated the generation of ATP and NADPH, which inhibited inflammatory cell infiltration, platelet activation, oxidative stress, and neuronal injury. This constructed nanoplatform not only showcases exceptional targeting efficiency at the stroke site and controllable release of the thrombolytic agent but also facilitates ATP/NADPH-mediated thrombolytic, anti-inflammatory, antioxidative stress, and neuroprotective effects. Additionally, it offers valuable insights into the potential therapeutic applications of microalgae-based derivatives in managing thromboembolic stroke.

Osteoporotic bone defects refer to the disruption of bone structural integrity in patients with osteoporosis and pose a substantial challenge to orthopedic surgeons. In this study, we developed a biomimetic hydrogel to improve the osteogenic microenvironment and promote stem cell homing. This hydrogel served as a container for S-nitrosoglutathione and Ca 2+ , promoting the release of bioactive nitric oxide (NO) from bone marrow mesenchymal stem cells (BMSCs) and human vascular endothelial cells and activating the NO/cyclic guanosine monophosphate signaling pathway. These changes promote osteogenic and angiogenic couplings. The hydrogel simultaneously recruited BMSCs by conjugating the stem cell homing peptide SKPPGTSS. Using a rat distal femoral defect model, it was demonstrated that this hydrogel can effectively increase the formation of bone tissue and new blood vessels and has immune-regulating functions. We envision that this hydrogel may be a minimally invasive yet highly effective strategy for expediting the healing of osteoporotic bone defects.

Wide used guided bone regeneration (GBR) membrane materials, such as collagen, Teflon, and other synthesized polymers, present a great challenge in term of integrating the mechanical property and degradation rate when addressing critical bone defects. Therefore, inspired by the distinctive architecture of fish scales, this study utilized epigallocatechin gallate to modify decellularized fish scales following biomimetic mineralization to fabricate a GBR membrane that mimics the structure of lamellar bone. The structure, physical and chemical properties, and biological functions of the novel GBR membrane were evaluated. Results indicate that the decellularized fish scale with 5 remineralization cycles (5R-E-DCFS) exhibited a composite and structure similar to natural bone and had a special functionally gradient mineral contents character, demonstrating excellent mechanical properties, hydrophilicity, and degradation properties. In vitro, the 5R-E-DCFS membrane exhibited excellent cytocompatibility promoting Sprague-Dawley (SD) rat bone marrow mesenchymal stem cell proliferation and differentiation up-regulating the expression of osteogenic-related genes and proteins. Furthermore, in vivo, the 5R-E-DCFS membrane promoted the critical skull bone defects of SD rats repairment and regeneration. Therefore, this innovative biomimetic membrane holds substantial clinical potential as an ideal GBR membrane with mechanical properties for space-making and suitable degradation rate for bone regeneration to manage bone defects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The distinctive composition and functions of osteochondral structures result in constrained regeneration. Insufficient healing processes may precipitate the emergence of tissue growth disorders or excessive subchondral bone formation, which can culminate in the deterioration and failure of osteochondral tissue repair. To overcome these limitations, materials designed for osteochondral repair must provide region-specific modulation of the microenvironment and mechanical compatibility. To address these challenges, we propose a method to create continuous hydrogels with distinct structural and functional properties by a precise cross-linking method. We have developed an innovative polyurethane enriched with dimethylglyoxime, facilitating the coordinated loading and precise release of Zn 2+ . This strategy enables the meticulous control of alginate cross-linking, resulting in an elastic gradient hydrogel that closely resembles the osteochondral interface. The SeSe within the hydrogel effectively modulates the inflammatory microenvironment and fosters the M2 polarization of macrophages. The hydrogel's lower layer is designed to rapidly release Zn 2+ , thereby enhancing bone regeneration. The upper layer is intended to prevent bone overgrowth and stimulate chondrogenic differentiation. This dual-layer strategy allows targeted stimuli to each region, promoting the seamless integration of neoosteochondral tissue. Our study demonstrates the potential of this stratified hydrogel in achieving uniform and smooth osteochondral tissue regeneration., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Despite the exceptional biocompatibility and degradability of Poly ( L -lactic acid) (PLLA), its brittleness, low melting strength, and poor bone induction makes it challenging to utilize for bone repair. This study used a simple, efficient solid hot drawing (SHD) method to produce high-strength PLLA, using supercritical CO 2 (SC-CO 2 ) foaming technology to give PLLA a bionic microporous structure to enhance its toughness, while precisely controlling micropore homogeneity and improving the melt strength by using Polydimethylsiloxane (PDMS). This PDMS-regulated oriented microporous structure resembled that of natural bone, displaying a maximum tensile strength of 165.9 MPa and a maximum elongation at break of 164.2 %. Furthermore, this bionic structure promoted the polarization of mouse bone marrow macrophages (iBMDM), exhibiting a simultaneous pro- and anti-inflammatory effect. This structure also contributed to the adhesion and growth of mouse embryonic fibroblasts (NIH-3 T3), promoting osteogenic differentiation, which paved the way for developing degradable PLLA bone-repair load-bearing materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Discectomy is the surgical standard of care to relieve low back pain caused by intervertebral disc (IVD) herniation. However, there remains annulus fibrosus (AF) defect and nucleus pulposus (NP) degeneration, which often result in recurrent herniation (re-herniation). Herein, we develop a polyphenol-modified waterborne polyurethane bioadhesives (PPU-glues) to promote therapy prognosis after discectomy. Being composed of tannic acid (TA) mixed cationic waterborne polyurethane nanodispersions (TA/WPU + ) and curcumin (Cur) embedded anionic waterborne polyurethane nanodispersions (Cur-WPU - ), PPU-glue gels rapidly (<10 s) and exhibits low swelling ratios, tunable degradation rates and good biocompatibility. Due to the application of an adhesion strategy combing English ivy mechanism and particle packing theory, PPU-glue also shows considerable lap shear strength against wet porcine skin (≈58 kPa) and burst pressure (≈26 kPa). The mismatched particle sizes and the opposite charges of TA/WPU + and Cur-WPU - in PPU-glue bring electrostatic interaction and enhance particle packing density. PPU-glue possesses superior reactive oxygen species (ROS)-scavenging capacity derived from polyphenols. PPU-glue can regulate extracellular matrix (ECM) metabolism in degenerated NP cells, and it can promote therapy biologically and mechanically in degenerated rat caudal discs. In summary, this study highlights the therapeutic approach that combines AF seal and NP augmentation, and PPU-glue holds great application potentials for post discectomy therapy. STATEMENT OF SIGNIFICANCE: Currently, there is no established method for the therapy of annulus fibrosus (AF) defect and nucleus pulposus (NP) degeneration after discectomy. Herein, we developed a polyphenol-modified biomimetic polyurethane bioadhesive (PPU-glue) with strong adhesive strength and superior bioactive property. The adhesion strategy that combined a particle packing theory and an English ivy mechanism was firstly applied to the intervertebral disc repair field, which benefited AF seal. The modified method of incorporating polyphenols was utilized to confer with ROS-scavenging capacity, ECM metabolism regulation ability and anti-inflammatory property, which promoted NP augmentation. Thus, PPU-glue attained the synergy effect for post discectomy therapy, and the design principle could be universally expanded to the bioadhesives for other surgical uses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Bacterial-induced lower respiratory tract infections are a growing global health concern, exacerbated by the inefficacy of conventional antibiotics and delivery methods to effectively target the lower respiratory tract, leading to suboptimal therapeutic outcomes. To address this challenge, this work engineers PBP2a antibody-presenting membrane nanovesicles (AMVs) specifically designed to target the penicillin-binding protein variant on the surface of methicillin-resistant Staphylococcus aureus (MRSA). Concurrently, this work develops pure ciprofloxacin nanoparticles (NanoCip) that, for the first time, exhibits exceptional self-generated sonodynamic properties, attributed to hydrogen-bond-driven self-assembly, while maintaining their inherent pharmacological efficacy. These NanoCip particles are integrated with AMVs to create a novel biomimetic nanomedicine, AMV@NanoCip. This formulation demonstrated remarkable MRSA-targeting affinity in both in vitro and in vivo models, significantly enhancing antibacterial activity. Upon ultrasound stimulation, AMV@NanoCip achieves over 99.99% sterilization of MRSA in vitro, with a reduction exceeding 5.14 Log CFU. Prokaryotic transcriptomic analysis further elucidates the synergistic mechanisms by which AMV@NanoCip, coupled with ultrasound, disrupts the MRSA exoskeleton. In a MRSA-induced pneumonia animal model, AMV@NanoCip+US results in a substantial bacterial load reduction in the lungs (99.99%, 4.02 Log CFU). This sequential treatment strategy (adhesion-membrane disruption-synergistic therapy) offers significant promise as an innovative therapeutic approach for combating bacterial infections., (© 2024 Wiley‐VCH GmbH.)

Developing multifunctional nanoplatforms to comprehensively modulate the tumor microenvironment and enhance diagnostic and therapeutic outcomes still remains a great challenge. Here, we report the facile construction of a multivariate nanoplatform based on cancer cell membrane (CM)-encapsulated redox-responsive poly(N-vinylcaprolactam) (PVCL) nanogels (NGs) co-loaded with Cu(II) and chemotherapeutic drug toyocamycin (Toy) for magnetic resonance (MR) imaging-guided combination tumor chemodynamic therapy/chemoimmunotherapy. We show that redox-responsive PVCL NGs formed through precipitation polymerization can be aminated, conjugated with 3,4-dihydroxyhydrocinnamic acid for Cu(II) complexation, physically loaded with Toy, and finally camouflaged with CMs. The created ADCT@CM NGs with an average size of 113.0 nm are stable under physiological conditions and can efficiently release Cu(II) and Toy under tumor microenvironment with a high level of glutathione. Meanwhile, the developed NGs are able to enhance cancer cell oxidative stress and endoplasmic reticulum stress by synergizing the effects of chemodynamic therapy mediated by Cu-based Fenton-like reaction and Toy-mediated chemotherapy, thereby triggering significant immunogenic cell death (ICD). In a melanoma mouse model, the NGs show potent immune activation effects to reinforce tumor therapeutic efficacy through ICD induction and immune modulation including high levels of immune cytokine secretion, increased tumor infiltration of CD8 + cytotoxic T cells, and reduced tumor infiltration of regulatory T cells. With the CM coating and Cu(II) loading, the developed NG platform demonstrates homologous tumor targeting and T 1 -weighted MR imaging, hence providing a general biomimetic NG platform for ICD-facilitated tumor theranostic nanoplatform. STATEMENT OF SIGNIFICANCE: Developing multifunctional nanoplatforms to comprehensively modulate the tumor microenvironment (TME) and enhance theranostic outcomes remains a challenge. Here, a cancer cell membrane (CM)-camouflaged nanoplatform based on aminated poly(N-vinylcaprolactam) nanogels (NGs) co-loaded with Cu(II) and toyocamycin (Toy) was prepared for magnetic resonance (MR) imaging-guided combination tumor chemodynamic therapy/chemoimmunotherapy. The tumor targeting specificity and efficient TME-triggered release of Cu(II) and Toy could enhance tumor cell oxidative stress and endoplasmic reticulum stress by synergizing the effects of chemodynamic therapy mediated by Cu-based Fenton-like reaction and Toy-mediated chemotherapy, respectively, thereby leading to significant immunogenic cell death (ICD) and immune response. With the CM coating and Cu(II) loading, the developed NG platform also demonstrates good T 1 -weighted tumor MR imaging performance. Hence, this study provides a general biomimetic NG platform for ICD-facilitated tumor theranostics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

After myocardial ischemia/reperfusion injury (MI/RI), endothelial cell injury causes impaired angiogenesis and obstruction of microcirculation, resulting in an inflammatory outburst that exacerbates the damage. Therefore, synergistic blood vessel repair and inflammation inhibition are effective therapeutic strategies. In this study, we developed a platelet membrane (PM)-encapsulated baicalin nanocrystalline (BA NC) nanoplatform with a high drug load, BA NC@PM, which co-target to endothelial cells and macrophages through the transmembrane proteins of the PM to promote angiogenesis and achieve anti-inflammatory effects. In vitro cell scratch assays and transwell assay manifested that BA NC@PM could promote endothelial cell migration, as well as increase mRNA expression of CD31 and VEGF in the heart after treatment of MI/RI mice, suggesting its favorable vascular repair function. In addition, the preparation significantly reduced the expression of pro-inflammatory factors and increased the expression of anti-inflammatory factors in plasma, promoting the polarization of macrophages. Our study highlights a strategy for enhancing the treatment of MI/RI by promoting angiogenesis and regulating macrophage polarization via the biomimetic BA NC@PM nanoplatform., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The study focuses on developing a bioactive shape memory sponge to address the urgent demand for short-term rapid hemostasis and long-term wound healing in noncompressible hemorrhage cases. A composite sponge was created by spontaneously generating pores and double cross-linking under mild conditions using biomimetic collagen fibril (BCF) and oxidized alginate (OA) as natural backbone, combined with an inert calcium source (Ca) from CaCO 3 -GDL slow gelation mechanism. The optimized BCF/OACa (5/5) sponge efficiently absorbed blood after compression and recovered to its original state within 11.2 ± 1.3 s, achieving physical hemostatic mechanism. The composite sponge accelerated physiological coagulation by promoting platelet adhesion and activation through BCF, as well as enhancing endogenous and exogenous hemostatic pathways by Ca 2+ . Compared to commercial PVA expanding hemostatic sponge, the composite sponge reduced bleeding volume and shortened hemostasis time in rat liver injury pick and perforation wound models. Additionally, it stimulated fibroblast migration and differentiation, thus promoting wound healing. It is biodegradable with low inflammatory response and promotes granulation tissue regeneration. In conclusion, this biocomposite sponge provides multiple hemostatic pathways and biochemical support for wound healing, is biologically safe and easy to fabricate, process and use, with significant potential for clinical translation and application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The hypoxic microenvironment within the tumor microenvironment of breast cancer imposes a challenge in overcoming chemotherapy resistance. In this investigation, we designed a novel strategy utilizing a light-controlled cascade targeting nanomedicine specifically tailored for enhanced immune therapy of breast cancer. Albumin nanoparticle was achieved by crosslinking, followed by loading TPZ and Ce6, and subsequent modification to enable selective binding with CD44 hyaluronic acid to form nanomedicine. Encouragingly, it was demonstrated the remarkable ability of the nanomedicine to effectively internalize into cellular entities, thereby inducing apoptosis in 4T1 cells efficiently in vitro when exposed to light irradiation. In vivo assessments showcased the exceptional aptitude of the nanomedicine not only for preferential accumulation within tumor tissues, but also for substantial suppression of tumor growth. Immune mechanisms have shown that nanomedicine treatment promoted the maturation of DCs in vivo, enhanced the proportion of CD8 + T cells in the spleen and tumor, and simultaneously upregulated the ratio of M1 macrophages favorable for anti-tumor effects. These outcomes collectively advance a fresh perspective for the clinical breast cancer therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study presents new injectable hydrogels based on hyaluronic acid and collagen type II that mimic the polysaccharide-protein structure of natural cartilage. After collagen isolation from chicken sternal cartilage, tyramine-grafted hyaluronic acid and collagen type II (HA-Tyr and COL-II-Tyr) were synthesized. Hybrid hydrogels were prepared with different ratios of HA-Tyr/COL-II-Tyr using horseradish peroxidase and noncytotoxic concentrations of hydrogen peroxide to encapsulate human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). The findings showed that a higher HA-Tyr content resulted in a higher storage modulus and a lower hydrogel shrinkage, resulting in hydrogel swelling. Incorporating COL-II-Tyr into HA-Tyr hydrogels induced a more favorable microenvironment for hBM-MSCs chondrogenic differentiation. Compared to HA-Tyr alone, the hybrid HA-Tyr/COL-II-Tyr hydrogel promoted enhanced chondrocyte adhesion, spreading, proliferation, and upregulation of cartilage-related gene expression. These results highlight the promising potential of injectable HA-Tyr/COL-II-Tyr hybrid hydrogels to deliver cells for cartilage regeneration., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mohammad J. Abdekhodaie reports financial support was provided by Council for Development of Stem Cell Sciences and Technologies. Mohammad J. Abdekhodaie reports financial support was provided by Iran National Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Herein, a ccRCC targeting nanodrug is designed to enhance chemodynamic therapy (CDT) as well as activate cuproptosis and tumor immunotherapy via ccRCC cell membrane modifying CuO@Gd 2 O 3 yolk-like particles (CGYL) loaded with lactate oxidase (LOx) (mCGYL-LOx). Benefiting from the homologous targeting effect of Renca cell membranes, the mCGYS-LOx can be effectively internalized by Renca cells, open the "gate", and then release LOx and copper (Cu) ions. LOx can catalyze excessive lactate in Renca cells into H 2 O 2 , following that the produced H 2 O 2 is further converted by Cu ions to the highly toxic ·OH, contributing to tumor CDT. Meanwhile, the excessive Cu ions effectively trigger tumor cuproptosis. These synergistic effects induce the release of damage associated molecular patterns (DAMPs) and activate immunogenic cell death (ICD), leading to DC maturation and infiltration of immune effector cells. Moreover, LOx-mediated lactate consumption downregulates the expression of PD-L1, crippling tumor immune escape. In addition, the mCGYL-LOx improves T 1 -weighted MRI signal, allowing for accurate diagnosis of ccRCC. This study demonstrates that the mCGYL-LOx has great potential for improving therapy of ccRCC via the synergistic actions of CDT and cuproptosis as well as immunotherapy., (© 2024 Wiley‐VCH GmbH.)

Rhamnolipids (RLs) and Fengycins (FGs) are biosurfactants with very promising antifungal properties proposed to reduce the use of synthetic pesticides in crops. They are amphiphilic molecules, both known to target the plasma membrane. They act differently on Botrytis cinerea and Sclerotinia sclerotiorum, two close Sclerotiniaceae phytopathogenic fungi. RLs are more efficient at permeabilizing S. sclerotiorum, and FGs are more efficient at permeabilizing B. cinerea mycelial cells. To study the link between the lipid membrane composition and the activity of RLs and FGs, we analyzed the lipid profiles of B. cinerea and S. sclerotiorum. We determined that unsaturated or saturated C18 and saturated C16 fatty acids are predominant in both fungi. We also showed that phosphatidylethanolamine (PE), phosphatidic acid (PA), and phosphatidylcholine (PC) are the main phospholipids (in this order) in both fungi, with more PA and less PC in S. sclerotiorum. The results were used to build biomimetic lipid membrane models of B. cinerea and S. sclerotiorum for all-atom molecular dynamic simulations and solid-state NMR experiments to more deeply study the interactions between RLs or FGs with different compositions of lipid bilayers. Distinctive effects are exerted by both compounds. RLs completely insert in all the studied model membranes with a fluidification effect. FGs tend to form aggregates out of the bilayer and insert individually more easily into the models representative of B. cinerea than those of S. sclerotiorum, with a higher fluidification effect. These results provide new insights into the lipid composition of closely related fungi and its impact on the mode of action of very promising membranotropic antifungal molecules for agricultural applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Nanomedicines have been widely used in colorectal cancer treatment, but their suboptimal targeting and deficient penetration capabilities remain obstacles in the delivery of therapeutics. In this study, inspired by the natural tumor tropism and intestinal invasion of Salmonella , we engineered highly biomimetic nanoparticles (SM-AuNRs) utilizing a Salmonella membrane to coat bacilliform Au nanorods. The engineered SM-AuNRs were able to mimic the germ's morphology and biological surface. SM-AuNRs containing the specific proteins inherited from the Salmonella membrane facilitated specific targeting and internalization into tumor cells. Meanwhile, SM-AuNRs with the rod-shaped morphology effectively traversed mucus barriers and tumor stroma. Due to the superior biological barrier penetrating and tumor targeting capabilities, doxorubicin-loaded SM-AuNRs with near-infrared laser irradiation displayed remarkable photothermal-chemotherapeutic antitumor effects in mouse orthotopic colorectal cancer models. Our findings pave the way for the design of bacteria-mimicking nanoparticles, presenting a promising avenue for the targeting and efficient treatment of colorectal cancer.

The self-assembly of lipopeptide (peptide amphiphile) molecules bearing single linear lipid chains has been widely studied, as has their diverse range of bioactivities. Here, we introduce lipopeptides bearing one or two cycloalkane chains (cycloheptadecyl or cyclododecyl) conjugated to the collagen-stimulating pentapeptide KTTKS used in Matrixyl formulations. The self-assembly of all four molecules is probed using fluorescence probe measurements to detect the critical aggregation concentration (CAC), and cryogenic-TEM and small-angle X-ray scattering (SAXS) to image the nanostructure. The peptide conformation is studied using circular dichroism (CD) and FTIR spectroscopies. All the cycloalkane lipopeptides show excellent compatibility with dermal fibroblasts. The compounds bearing one or two cyclododecyl chains (denoted as DKT and DDKT, respectively) show wound healing in diabetic rats, the improvement being markedly enhanced for DDKT. Interestingly, the revival of hair follicles and blood vessels in the dermis were observed, which are the critical markers of effective wound repair. Analysis of H&E-stained tissue images (from a rat model) shows that the rat groups treated with DDKT and DKT displayed a significantly increased amount of regenerated hair follicles, indicating a faster healing process for DDKT compared to the control group. Collagen deposition was also enhanced, especially for DDKT, and by day 20, the DDKT-treated groups had developed a dense collagen network accompanied by a regenerated epidermis. At the same time, the number of blood vessels in DDKT-treated diabetic wounds was significantly higher than in control groups and neovascularization was substantially enhanced, as assayed using α-SMA (a marker for vascular smooth muscle cells) and CD31 (a marker specific to vascular endothelial cells). These results suggest that the lead lipopeptide DDKT exhibits a remarkable pro-vascularization capability and shows great promise for future application as a wound-healing biomaterial.

Postoperative radiotherapy currently stands as the cornerstone of glioblastoma (GBM) treatment. Nevertheless, low-dose radiotherapy has been proven ineffective for GBM, due to hypoxia in the GBM microenvironment, which renders the resistance to radiation-induced cell death. Moreover, the overexpression of the PLK1 gene in glioma cells enhances GBM proliferation, invasion, metastasis, and resistance to radiation. This study introduced a hybrid membrane-camouflaged biomimetic lipid nanosensitizer (CNL@miPA), which efficiently encapsulated gold nanoclusters (PA) and miR-593-5p by a chimeric membrane derived from lipids, cancer cells, and natural killer cells. CNL@miPA exhibited exceptional blood-brain barrier and tumor tissue penetration, effectively ameliorating hypoxia and synergizing with radiotherapy. By enabling prolonged miRNA circulation in the bloodstream and achieving high enrichment at the tumor site, CNL@miPA significantly suppressed tumor growth in combination treatment, thereby significantly extending the survival period of treated mice. Overall, the developed biomimetic nanosensitizer represented an efficient and multifunctional targeted delivery system, offering a novel strategy for gene-radiotherapy of GBM.

Electrical stimulation has been used clinically as an adjunct therapy to accelerate the healing of bone defects, and its mechanism requires further investigations. The complexity of the physiological microenvironment makes it challenging to study the effect of electrical signal on cells alone. Therefore, an artificial system mimicking cell microenvironment in vitro was developed to address this issue. In this work, a novel electrical stimulation system was constructed based on polypyrrole nanowires (ppyNWs) with a high aspect ratio. Synthesized ppyNWs formed a conductive network in the composited hydrogel which contained modified gelatin with methacrylate, providing a conductive cell culture matrix for bone marrow mesenchymal stem cells. The dual-network conductive hydrogel had improved mechanical, electrical, and hydrophilic properties. It was able to imitate the three-dimensional structure of the cell microenvironment and allowed adjustable electrical stimulations in the following system. This hydrogel was integrated with cell culture plates, platinum electrodes, copper wires, and external power sources to construct the artificial electrical stimulation system. The optimum voltage of the electrical stimulation system was determined to be 2 V, which exhibited remarkable biocompatibility. Moreover, this system had significant promotion in cell spreading, osteogenic makers, and bone-related gene expression of stem cells. RNA-seq analysis revealed that osteogenesis was correlated to Notch, BMP/Smad, and calcium signal pathways. It was proven that this biomimetic system could regulate the osteogenesis procedure, and it provided further information about how the electrical signal regulates osteogenic differentiations.

Alzheimer's disease (AD) is a common neurodegenerative disease characterized by progressive cognitive and physical impairment. Neuroinflammation is related to AD, and the misfolding and aggregation of amyloid protein in the brain creates an inflammatory microenvironment. Microglia are the predominant contributors to neuroinflammation, and abnormal activation of microglia induces the release of a large amount of inflammatory factors, promotes neuronal apoptosis, and leads to cognitive impairment. In this study, we used microglial membranes containing caffeic acid-coupled carbon quantum dots to prepare a novel biomimetic nanocapsule (CDs-CA-MGs) for the treatment of AD. The application of CDs-CA-MGs via nasal administration can bypass the blood‒brain barrier (BBB) and directly target the site of inflammation. After treatment with CDs-CA-MGs, AD mice showed reduced inflammation in the brain, decreased neuronal apoptosis, and significantly improved learning and memory abilities. In addition, CDs-CA-MGs affect inflammation-related JAK-STAT and Toll-like receptor signaling pathways in AD mice. CDs-CA-MGs significantly downregulated interleukins (IL-1β and IL-6) and tumor necrosis factor (TNF-α). This finding suggested that CDs-CA-MGs may improve cognitive impairment by modulating inflammatory responses. In conclusion, the use of CDs-CA-MGs provides a possible therapeutic strategy for the treatment of AD., (© 2024. The Author(s).)

Diabetes mellitus (DM) is a chronic metabolic condition, characterized by hyperglycaemia, oxidative imbalance, pancreatic β-cell death, and insulin insufficiency. Angiotensin II (Ang II) increases oxidative stress, inflammation, and apoptosis, and Ang II type 1 receptor (AT1R) blockers (ARBs) can ameliorate inflammatory response and oxidative stress. However, like other small-molecule drugs, free ARBs show poor in vivo efficacy and dose-limiting toxicities. Hence, in this study, we developed nano-formulations of telmisartan (TEL), an ARB, by encapsulating it inside a murine insulinoma cell-derived extracellular vesicle (nanoTEL) and a bio-mimetic lipid nanovesicle (lipoTEL). Both nano-formulations showed spherical morphology and sustained release of TEL. In vitro , nanoTEL restored oxidative equilibrium, attenuated reactive oxygen species levels, enhanced the uptake of glucose analogue, and increased the expression of glucose transporter protein 4 better than lipoTEL. In a streptozotocin-induced murine model of diabetes, nanoTEL lowered blood glucose levels, improved glucose tolerance, and promoted insulin synthesis and secretion significantly better than lipoTEL. Moreover, nanoTEL was found superior in ameliorating the pancreatic inflammatory microenvironment by regulating NF-κBp65, HIF-1α, and PPAR-γ expression; modulating IL-1β, IL-6, tumor necrosis factor-α, IL-10, and IL-4 levels and inducing the polarization of macrophage from M1 to M2. Further, nanoTEL administration induced angiogenesis and promoted the proliferation of pancreatic cells to restore the structural integrity of the islets of Langerhans more efficiently than lipoTEL. These findings collectively suggest that nanoTEL outperforms lipoTEL in restoring the function of pancreatic β-cells by modulating the pancreatic inflammatory microenvironment and show potential for the treatment of DM.

Sepsis-associated encephalopathy (SAE) is a devastating complication of sepsis, affecting approximately 70% of patients with sepsis in intensive care units (ICU). Although the pathophysiological mechanisms remain elusive, sepsis is typically accompanied by systemic inflammatory response syndrome (SIRS) and hyper-oxidative conditions. Here, we introduce a biomimetic nanomodulator (mAOI NP) that specifically targets inflammation site and simultaneously regulates oxidative and inflammatory stresses. mAOI NPs are constructed using metal-coordinated polyphenolic antioxidants (tannic acid) and flavonoid quercetin, which are then coated with macrophage membrane to enhance pharmacokinetics and enable SAE targeting. In a cecal ligation and puncture (CLP)-induced severe sepsis model, mAOI NPs effectively mitigate oxidative stress by purging reactive oxygen species, repairing mitochondrial damage and activating the Nrf2/HO-1 signaling pathway; while polarizing M1 macrophages or microglia toward anti-inflammatory M2 subtype. mAOI NPs potently inhibit sepsis progress, prolong overall survival from 25 to 66% and enhance learning and memory capabilities in SAE mice. Further proteomics analysis reveals that mAOI NPs modulate neurodevelopment processes related to learning and memory formation while also exerting anti-inflammatory and antioxidative effects on brain tissue responses associated with SAE pathology. This study offers significant potential for improving patient outcomes and revolutionizing the treatment landscape for this devastating complication of sepsis.

Failure of articular cartilage lubrication and inflammation are the main causes of osteoarthritis (OA), and integrated treatment realizing joint lubrication and anti-inflammation is becoming the most effective treat model. Inspired by low friction of human synovial fluid and adhesive chemical effect of mussels, our work reports a biomimetic lubricating system that realizes long-time lubrication, photothermal responsiveness and anti-inflammation property. To build the system, a dopamine-mediated strategy is developed to controllably graft hyaluronic acid on the surface of metal organic framework. The design constructs a biomimetic core-shell structure that has good dispersity and stability in water with a high drug loading ratio of 99%. Temperature of the solution rapidly increases to 55 °C under near-infrared light, and the hard-soft lubricating system well adheres to wear surfaces, and greatly reduces frictional coefficient by 75% for more than 7200 times without failure. Cell experiments show that the nanosystem enters cells by endocytosis, and releases medication in a sustained manner. The anti-inflammatory outcomes validate that the nanosystem prevents the progression of OA by down-regulating catabolic proteases and pain-related genes and up-regulating genes that are anabolic in cartilage. The study provides a bioinspired strategy to employ metal organic framework with controlled surface and structure for friction reduction and anti-inflammation, and develops a new concept of OA synergistic therapy model for practical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The repair of critical-sized bone defects remains a major challenge for clinical orthopedic surgery. Here, we develop a surface biofunctionalized three-dimensional (3D) porous polyether-ether-ketone (PEEK) scaffold that can simultaneously promote osteogenesis and regulate macrophage polarization. The scaffold is created using polydopamine (PDA)-assisted immobilization of silk fibroin (SF) and the electrostatic self-assembly of nanocrystalline hydroxyapatite (nano-HA) on a 3D-printed porous PEEK scaffold. The SF/nano-HA functionalized surface provides a bone-like microenvironment for osteoblastic cells' adhesion, proliferation, mineralization and osteogenic differentiation. Moreover, the biofunctionalized surface can effectively drive macrophages polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Integrin β1-specific cell-matrix binding and the activation of Ca 2+ receptor-mediated signaling pathway play critical roles in the regulation of macrophage polarization. Compared with the as-printed scaffold, the SF/nano-HA functionalized porous PEEK scaffold induces minimal inflammatory response, enhanced angiogenesis, and substantial new bone formation, resulting in improved osseointegration in vivo . This study not only develops a promising candidate for bone repair but also demonstrates a facile surface biofunctionalization strategy for orthopedic implants to improve osseointegration by stimulating osteogenesis and regulating immunity.

Mussel refers to a marine organism with strong adhesive properties, and it secretes mussel adhesion protein (MAP). The most vital feature of MAP is the abundance of the 3,4-dihydroxyphenylalanine (DOPA) group and lysine, which have antimicrobial, anti-inflammatory, antioxidant, and cell adhesion-promoting properties and can accelerate wound healing. Polydopamine (PDA) is currently the most widely used mussel-inspired material characterized by good adhesion, biocompatibility, and biodegradability. It can mediate various interactions to form functional coatings on cell-material surfaces. Nanofibers based on MAP and mussel-inspired materials have been exerting a vital role in wound repair, while there is no comprehensive review presenting them. This Review introduces the structure of MAPs and their adhesion mechanisms and mussel-inspired materials. Second, it introduces the functionalized modification of MAPs and their inspired materials in electrospun nanofibers and application in wound repair. Finally, the future development direction and coping strategies of MAP and mussel-inspired materials are discussed. Moreover, this Review can offer novel strategies for the application of nanofibers in wound repair and bring about new breakthroughs and innovations in tissue engineering and regenerative medicine.

The advancement of antithrombotic materials has significantly mitigated the thrombosis issue in clinical applications involving various medical implants. Extensive research has been dedicated over the past few decades to developing blood-contacting materials with complete resistance to thrombosis. However, despite these advancements, the risk of thrombosis and other complications persists when these materials are implanted in the human body. Consequently, the modification and enhancement of antithrombotic materials remain pivotal in 21st-century hemocompatibility studies. Previous research indicates that the healthy endothelial cells (ECs) layer is uniquely compatible with blood. Inspired by bionics, scientists have initiated the development of materials that emulate the hemocompatible properties of ECs by replicating their diverse antithrombotic mechanisms. This review elucidates the antithrombotic mechanisms of ECs and examines the endothelium-mimicking materials developed through single, dual-functional and multifunctional strategies, focusing on nitric oxide release, fibrinolytic function, glycosaminoglycan modification, and surface topography modification. These materials have demonstrated outstanding antithrombotic performance. Finally, the review outlines potential future research directions in this dynamic field, aiming to advance the development of antithrombotic materials.

Reprogramming of cellular metabolism in tumors promoted the epithelial-mesenchymal transition (EMT) process and established immune-suppressive tumor microenvironments (iTME), leading to drug resistance and tumor progression. Therefore, remodeling the cellular metabolism of tumor cells was a promising strategy to overcome drug-resistant tumors. Herein, CD276 and MTHFD2 were identified as a specific marker and a therapeutic target, respectively, for targeting sunitinib-resistant clear cell renal cell carcinoma (ccRCC) and its cancer stem cell (CSC) population. The blockade of MTHFD2 was confirmed to overcome drug resistance via remodeling of folate-nucleotide metabolism. Moreover, the manganese dioxide nanoparticle was proven here by a high-throughput metabolome to be capable of remodeling γ-aminobutyric acid (GABA) metabolism in tumor cells to reconstruct the iTME. Based on these findings, engineered CD276-CD133 dual-targeting biomimetic nanovesicle EMφ-siMTHFD2-MnO 2 @Suni was designed to overcome drug resistance and terminate tumor progression of ccRCC. Using ccRCC-bearing immune-humanized NPG model mice, EMφ-siMTHFD2-MnO 2 @Suni was observed to remodel folate-nucleotide and GABA metabolism to deactivate the EMT process and reconstruct the iTME thereby overcoming the drug resistance. In the incomplete-tumor-resection recurrence model and metastasis model, EMφ-siMTHFD2-MnO 2 @Suni reduced recurrence and metastasis in vivo. This work thus provided an innovative approach that held great potential in the treatment of drug-resistant ccRCC by remodeling cellular metabolism.

Rationale: The clinical treatment of epilepsy is faced with challenges. On the one hand, the effectiveness of existing antiepileptic drugs (AEDs) is limited by the blood‒brain barrier (BBB); on the other hand, changes in the inflammatory microenvironment during epileptogenesis are often neglected. Methods: The death-associated protein kinase 1 inhibitor TC-DAPK6 and the fluorescent probe rhodamine B were encapsulated in hollow mesoporous silica nanocarriers (HMSNs), which were then coated with a macrophage membrane to prepare macrophage membrane-biomimetic nanoparticles, namely, MA@RT-HMSNs. In vitro biotoxicity, cellular uptake, BBB permeability and inflammatory targeting ability were evaluated in cells. The effects of MA@RT-HMSN treatment were explored by immunohistochemistry, TUNEL assay, Western blot analysis, quantitative real-time polymerase chain reaction, electroencephalogram recording and behavioural tests in kainic acid-induced acute and chronic epilepsy model mice. Results: MA@RT-HMSNs showed excellent biocompatibility both in vitro and in vivo . MA@RT-HMSNs successfully crossed the BBB and exhibited increased efficacy in targeted delivery of TC-DAPK6 to inflammatory lesions in epileptic foci. Macrophage membrane coating conferred MA@RT-HMSNs with higher stability, greater cellular uptake, and enhanced TC-DAPK6 bioavailability. Furthermore, MA@RT-HMSNs exerted beneficial therapeutic effects on acute and chronic epilepsy models by alleviating microenvironment inflammation, preventing neuronal death, and inhibiting neuronal excitability and gliosis. Conclusions: MA@RT-HMSNs target inflammatory foci to inhibit death-related protein kinase 1 and exert antiepileptic effects. This study provides a promising biomimetic nanodelivery system for targeted epilepsy therapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Inspired by the concept of "natural camouflage," biomimetic drug delivery systems have emerged to address the limitations of traditional synthetic nanocarriers, such as poor targeting, susceptibility to identification and clearance, inadequate biocompatibility, low permeability, and systemic toxicity. Biomimetic nanocarriers retain the proteins, nucleic acids, and other components of the parent cells. They not only facilitate drug delivery but also serve as communication media to inhibit tumor cells. This paper delves into the communication mechanisms between various cell-derived biomimetic nanocarriers, tumor cells, and the tumor microenvironment, as well as their applications in drug delivery. In addition, the additional communication capabilities conferred on the modified biomimetic nanocarriers, such as targeting and environmental responsiveness, are outlined. Finally, we propose future development directions for biomimetic nanocarriers, hoping to inspire researchers in their design efforts and ultimately achieve clinical translation., (© 2024. The Author(s).)

Effective, precise, and controllable oxygen delivery is crucial for regulating the oxygenation balance of brain tissue at the early stages of acute ischemic stroke (AIS) because the absence of oxygen may result in a series of highly interconnected vascular-neural pathological events, including oxidative stress, inflammation, and neuroapoptosis. In this study, platelet membrane-reassembled oxygen nanobubbles (PONBs) were constructed for oxygen delivery to protect AIS. Benefiting from the preserved natural targeting ability of platelet membranes, oxygen can be controlled release into the hypoxia lesion at the preperfusion stage due to vascular injury targeting and oxygen sustained diffusion capability after PONBs administration. Furthermore, synergizing with bioactive components carried by platelet membranes, PONBs can inhibit post-AIS vascular occlusion and maintain blood-brain barrier integrity, thereby facilitating enhanced oxygen delivery of PONBs, establishing a positive feedback loop between oxygen delivery and AIS protection. Additionally, the accumulation of PONBs enhances the ultrasound imaging contrast, enabling precise localization and dynamic monitoring of AIS lesions. Thus, PONBs represent a promising strategy for the diagnosis and treatment of AIS.

The demand for synthetic soft materials with bioinspired structures continues to grow. Material applications range from in vitro and in vivo tissue mimics to therapeutic delivery systems, where well-defined synthetic building blocks offer precise and reproducible property control. This work examines a synthetic assembling peptide, specifically a multifunctional collagen mimetic peptide (mfCMP) either alone or with reactive macromers, for the creation of responsive hydrogels that capture aspects of soft collagen-rich tissues. We first explored how buffer choice impacts mfCMP hierarchical assembly, in particular, peptide melting temperature, fibril morphology, and ability to form physical hydrogels. Assembly in physiologically relevant buffer resulted in collagen-like fibrillar structures and physically assembled hydrogels with shear-thinning (as indicated through strain-yielding) and self-healing properties. Further, we aimed to create fully synthetic, composite peptide-polymer hydrogels with dynamic responses to various stimuli, inspired by the extracellular matrix (ECM). Specifically, we established mfCMP-poly(ethylene glycol) (PEG) hydrogel compositions that demonstrate increasing non-linear viscoelasticity in response to applied strain as the amount of assembled mfCMP content increases. Furthermore, the thermal responsiveness of mfCMP physical crosslinks was harnessed to manipulate the composite hydrogel mechanical properties in response to changes in temperature. Finally, cells relevant in wound healing, human lung fibroblasts, were encapsulated within these peptide-polymer hydrogels to explore the impact of increased mfCMP, and the resulting changes in viscoelasticity, on cell response. This work establishes mfCMP building blocks as versatile tools for creating hybrid and adaptable systems with applications ranging from injectable shear-thinning materials to responsive interfaces and synthetic ECMs for tissue engineering.

Changes in the expression of cornified envelope (CE) components are a hallmark of numerous pathological skin conditions and aging, underlying the importance of this stratum corneum structure in the homeostasis of the epidermal barrier. We performed a detailed characterisation of LCE6A, a member of the Late Cornified Envelope protein family. Immunohistochemical and immunoblot experiments confirmed that LCE6A is expressed late during epidermal differentiation. Crosslinking assays of recombinant LCE6A performed either in situ on human skin sections or in vitro demonstrated that LCE6A is indeed a substrate of transglutaminases and crosslinked to CEs. LCE6A-derived peptides containing a glutamine-lysine sequence retained these properties of the full-length protein and reinforced the mechanical resistance of CE submitted to sonication. We designed P26, a LCE6A-derived biomimetic peptide that similarly reinforced CE in vitro, and evaluated its protective properties ex vivo, on human skin explants, and in two double blind and vehicle-controlled clinical trials. P26 was able to protect the skin from barrier disruption, to limit the damage resulting from a defective barrier, and could improve the signs of aging such as loss of skin firmness and increased skin roughness. Hence, our detailed characterisation of LCE6A as a component of the CE enabled us to develop a LCE6A-derived peptide, biologically active with a new and original mode of action that could be of great interest as a cosmetic ingredient and a pharmacologic agent., (© 2024 The Author(s). Experimental Dermatology published by John Wiley & Sons Ltd.)

The biomimetic nanoparticles (NPs) possessing abilities of tumor targeting and multimodal therapy show great potential for efficient combat of colon cancer. Herein, we developed a multifunctional biomimetic nanoplatform (Fe 3 O 4 @PDA@CaCO 3 -ICG@CM) based on CaCO 3 -modified magnetic polydopamine (PDA) loaded with indocyanine green (ICG), which was encapsulated by a mouse lymphoma cell (EL4) membrane (CM) expressing functional proteins (i.e., lymphocyte function-associated antigen 1, LFA-1; transforming growth factor-β receptor, TGF-βR; programmed cell death protein 1, PD-1; and factor related apoptosis ligand, FasL). Under magnetic attraction and LFA-1/PD-1-mediated endocytosis, Fe 3 O 4 @PDA@CaCO 3 -ICG@CM efficiently targeted CT26 colon tumor cells. The released calcium ion (Ca 2+ ) from the NPs triggered by acidic tumor microenvironment, the enhanced photothermal effect contributed by the combination of PDA and ICG, and FasL's direct killing effect together induced tumor cells apoptosis. Moreover, the apoptosis of CT26 cells induced immunogenic cell death (ICD) to promote the maturation of dendritic cells (DCs) to activate CD4 + /CD8 + T cells, thereby fighting against tumor cells, which could further be boosted by programmed death-ligand 1 (PD-L1) blockage and transforming growth factor-β (TGF-β) scavenging by Fe 3 O 4 @PDA@CaCO 3 -ICG@CM. As a result, in vivo satisfactory therapeutic effect was observed for CT26 tumor bearing-mice treated with Fe 3 O 4 @PDA@CaCO 3 -ICG@CM under laser irradiation and magnetic attraction, which could eradicate primary tumors and restrain distant tumors through dual tumor targeting-assisted multimodal therapy and eliciting adaptive antitumor immune response, generating the immune memory for inhibiting tumor metastasis and recurrence. Taken together, the multifunctional biomimetic nanoplatform exhibits superior antitumor effects, providing an insightful strategy for the field of nanomaterial-based treatment of cancer.

Infected bone defects are one of the most challenging problems in the treatment of bone defects due to the high antibiotic failure rate and the lack of ideal bone grafts. In this paper, inspired by clinical bone cement filling treatment, α-c phosphate (α-TCP) with self-curing properties is composited with β-tricalcium phosphate (β-TCP) and constructed a bionic cancellous bone scaffolding system α/β-tricalcium phosphate (α/β-TCP) by low-temperature 3D printing, and gelatin is preserved inside the scaffolds as an organic phase, and later loaded with a metal-polyphenol network structure of tea polyphenol-magnesium (TP-Mg) nanoparticles. The scaffolds mimic the structure and components of cancellous bone with high mechanical strength (>100 MPa) based on α-TCP self-curing properties through low-temperature 3D printing. Meanwhile, the scaffolds loaded with TP-Mg exhibit significant inhibition of Staphylococcus aureus (S.aureus) and promote the transition of macrophages from M1 pro-inflammatory to M2 anti-inflammatory phenotype. In addition, the composite scaffold also exhibits excellent bone-enhancing effects based on the synergistic effect of Mg 2+ and Ca 2+ . In this study, a multifunctional ceramic scaffold (α/β-TCP@TP-Mg) that integrates anti-inflammatory, antibacterial, and osteoinduction is constructed, which promotes late bone regenerative healing while modulating the early microenvironment of infected bone defects, has a promising application in the treatment of infected bone defects., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Targeting phospholipid biosynthesis, specifically phosphatidylcholine (PC), which is enhanced in tumor cells, has been proven a suitable antitumor strategy. In fact, the overexpression of the choline kinase α1 (ChoKα1) isoform has been found in malignant cells and tumors, thus becoming an excellent antitumor target. ChoKα1 inhibitors are being synthesized at the present that show a large inhibitory activity. Two of them have been chosen in this study as representatives of different structural families: a biscationic biphenyl derivative of thieno[3,2-d]pyrimidinium substituted with a cyclic amine (here referred to as Fa22) and a biscationic biphenyl thioethano derivative of 7-chloro-quinolinium substituted with a pyrrolidinic moiety (here referred to as PL48). However, the potential use of these types of compounds in systemic treatments is hampered because of their low specificity. In fact, to enter the cell and reach their target, these inhibitors use choline transporters and inhibit choline uptake, being that one of the causes of their toxicity. One way to solve this problem could be allowing their entrance into the cells by alternative ways. With this goal, MamC-mediated magnetic nanoparticles (BMNPs), already proven effective drug nanocarriers, have been used to immobilize Fa22 and PL48. The idea is to let BMNPs enter the cell (they enter the cell by endocytosis) carrying these molecules, and, therefore, offering another way in for these compounds. In the present study, we demonstrate that the coupling of Fa22 and PL48 to BMNPs allows these molecules to enter the tumoral cell without completely inhibiting choline uptake, so, therefore, the use of Fa22 and PL48 in these nanoformulations reduces the toxicity compared to that of the soluble drugs. Moreover, the nanoassemblies Fa22-BMNPs and PL48-BMNPs allow the combination of chemotherapy and local hyperthermia therapies for a enhanced cytotoxic effect on the tumoral HepG2 cell line. The consistency of the results, independently of the drug structure, may indicate that this behavior could be extended to other ChoKα1 inhibitors, opening up a possibility for their potential use in clinics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

An interbody fusion cage (Cage) is crucial in spinal decompression and fusion procedures for restoring normal vertebral curvature and rebuilding spinal stability. Currently, these Cages suffer from issues related to mismatched elastic modulus and insufficient bone integration capability. Therefore, a gel-casting technique is utilized to fabricate a biomimetic porous titanium alloy material from Ti6Al4V powder. The biomimetic porous Ti6Al4V is compared with polyetheretherketone (PEEK) and 3D-printed Ti6Al4V materials and their respective Cages. Systematic validation is performed through mechanical testing, in vitro cell, in vivo rabbit bone defect implantation, and ovine anterior cervical discectomy and fusion experiments to evaluate the mechanical and biological performance of the materials. Although all three materials demonstrate good biocompatibility and osseointegration properties, the biomimetic porous Ti6Al4V, with its excellent mechanical properties and a structure closely resembling bone trabecular tissue, exhibited superior bone ingrowth and osseointegration performance. Compared to the PEEK and 3D-printed Ti6Al4V Cages, the biomimetic porous Ti6Al4V Cage outperforms in terms of intervertebral fusion performance, achieving excellent intervertebral fusion without the need for bone grafting, thereby enhancing cervical vertebra stability. This biomimetic porous Ti6Al4V Cage offers cost-effectiveness, presenting significant potential for clinical applications in spinal surgery., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Triple negative breast cancer (TNBC) featuring high relapses and metastasis shows limited clinical therapeutic efficiency with chemotherapy for the extremely complex tumor microenvironment, especially angiogenesis and immunosuppression. Combination of antiangiogenesis and immunotherapy holds promise for effective inhibition of tumor proliferation and invasion, while it remains challenging for specific targeting drug delivery to tumors and metastatic lesions. Here, a multifunctional biomimetic liposome loading Gambogic acid (G/R-MLP) is developed using Ginsenoside Rg3 (Rg3) to substitute cholesterol and cancer cell membrane coating, which is designed to increase long-circulating action by a low immunogenicity and specifically deliver gambogic acid (GA) to tumor site and metastatic lesions by homologous targeting and glucose transporter targeting. After G/R-MLP accumulates in the primary tumors and metastatic nodules, it synergistically enhances the antitumor efficacy of GA, effectively suppressing the tumor growth and lung metastasis by killing tumor cells, inhibiting tumor cell migration and invasion, achieving antiangiogenesis and improving the antitumor immunity. All in all, the strategy combining chemotherapy, antiangiogenesis, and immunotherapy improves therapeutic efficiency and prolonged survival, providing a new perspective for the clinical treatment of TNBC., (© 2024 Wiley‐VCH GmbH.)

Enzymatic browning and microbial contamination of food threaten food sensory and safety. With the development of green and healthy concepts, there is a greater need for efficient, low-carbon antioxidant and antimicrobial strategies. In this study, we designed a nano-enzyme with antioxidant activities and biocompatibility. By mimicking the active center of the natural SOD enzyme, copper (Cu) and ovalbumin (OVA) were self-assembled to form Cu-nano-polymerised sheet (Cu-NPS), in which OVA as a scaffold carries cofactors to create the active sites, making the nanoenzymes compatible with the antioxidant activity and antimicrobial properties of Cu, and at the same time possessing good stability and biocompatibility. These properties enable Cu-NPS to have a broader application range, for removing reactive oxygen species (ROS) and broad-spectrum sterilization. Subsequently, Cu-NPS was doped into carrageenan (Carr) to form a nanocomposite film, effectively inhibiting enzymatic browning and microbial contamination. In this work, protein-based mimetic enzymes as artificial nanoenzymes have advantages over natural enzymes, and the Cu-NPS with simple synthesis, high stability, and diverse properties, provides new ideas for the design of functional materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Acute kidney injury (AKI) is the sudden decrease in renal function that can be attributed to dysregulated reactive oxygen species (ROS) production and impaired mitochondrial function. Irisin, a type I membrane protein secreted by skeletal muscles in response to physical activity, has been reported to alleviate kidney damage through regulation of mitochondrial biogenesis and oxidative metabolism. In this study, a macrophage membrane-coated metal-organic framework (MCM@MOF) is developed as a nanocarrier for encapsulating irisin to overcome the inherent characteristics of irisin, including a short circulation time, limited kidney-targeting ability, and low membrane permeability. The engineered irisin-mediated biomimetic nanotherapeutics have extended circulation time and enhanced targeting capability toward injured kidneys due to the preservation of macrophage membrane proteins. The irisin-encapsulated biomimetic nanotherapeutics effectively mitigate acute ischemia-reperfusion injury by protecting mitochondrial function and modulating SOD2 levels in renal tubular epithelial cells. The present study provides novel insights to advance the development of irisin as a potential therapeutic approach for AKI., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The avascular nature of cartilage tissue limits inherent regenerative capacity to counter any damage and this has become a substantial burden to the health of individuals. As a result, there is a high demand to repair and regenerate cartilage. Existing tissue engineering approaches for cartilage regeneration typically produce either microporous or nano-fibrous scaffolds lacking the desired biological outcome due to lack of biomimetic dual architecture of microporous construct with nano-fibrous interconnected structures like the native cartilage. Most of these scaffolds also fail to suppress ROS generation and provide sustained bioenergetics to cells, resulting in the loss of metabolic activity under avascular microenvironment of cartilage. A dual architecture microporous construct with nano-fibrous interconnected network of cellulose aerogel reinforced with arginine-coated graphene oxide (CNF-GO-Arg aerogel) was developed for cartilage regeneration. The designed dual-architectured CNF-GO-Arg aerogel using dual ice templating assembly demonstrates 80 % strain recovery ability under compression. The release of Arginine from CNF-GO-Arg aerogel supported 41 % reduction in intracellular ROS activity and promoted chondrogenic differentiation of hMSCs by shifting mitochondrial bioenergetics towards oxidative phosphorylation indicated by JC-1 dye staining. Overall developed CNF-GO-Arg aerogel provided multifunctionality via biomimetic morphology, cellular bioenergetics, and suppressed ROS generation to address the need for regeneration of cartilage., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A novel laccase mimic enzyme Cu-Mn with excellent photothermal properties was firstly prepared via a combination of hydrothermal and in situ synthesis. Cu-Mn nanozymes could catalyze the typical laccase substrate 2,4-dichlorophenol (2,4-DP) to generate the red quinone imine. Further, loading the MnO 2 nanosheets with photothermal properties, Cu-Mn nanozymes possessed not only excellent laccase catalytic activity, but also high photothermal conversion efficiency. The presence of glutathione S-transferase (GST) recovered the glutathione (GSH)-induced weakness of the laccase activity and photothermal properties of Cu-Mn. Hence, a GST enzyme-regulated dual-mode sensing strategy was established based on Cu-Mn nanozymes. The detection limits of GST monitoring based on colorimetric and photothermal methods were 0.092 and 0.087 U/L with response times of 20 min and 8 min, respectively. Furthermore, the proposed method enabled the measuring of GST levels in human serum and was successfully employed in the primary evaluation of hepatitis patients. Another attraction, the impressive photothermal behavior also endowed the Cu-Mn nanozymes with promising antimicrobial properties, which exhibited significant antimicrobial effects against Escherichia coli (E.coli) and Staphylococcus aureus (S.aureus). Unsurprisingly, multifunctional Cu-Mn nanozymes certainly explore new paths in biochemical analysis and antimicrobial applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)