Visualization of nasal powder distribution using biomimetic human nasal cavity model

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

Antibacterial copper sulfide/graphene oxide nanosheets composite film promotes angiogenic and osteogenic differentiation in vitro / 中华创伤骨科杂志

Objective:To investigate whether the antibacterial copper sulfide (CuS)/graphene oxide (GO) nanosheets composite film can promote angiogenesis and osteogenesis in vitro. Methods:GO and CuS/GO nanosheets were synthesized and mixed into polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC) hydrogel films. The study was conducted in 4 groups: PVA/CMC/GO, PVA/CMC/CuS/GO, PVA/CMC (only PVA/CMC-based film) and blank control (no material). The PVA/CMC, PVA/CMC/GO and PVA/CMC/CuS/GO films were characterized by electron scanning microscopy and energy dispersive spectrometer. The biocompatibility of different films (PVA/CMC/CuS/GO films with concentrations of CuS/GO nanotablets of 0, 50, 100, 200, 400, and 800 μ g/mL) was evaluated by CCK-8, live/dead cell staining, and hemolysis test. The angiogenesis was evaluated by cell migration and tube forming test in vitro. Alkaline phosphatase and alizarin red staining were used to evaluate osteogenesis in vitro, and the expression of osteogenic genes was measured by immunofluorescence staining and RT-qPCR. In addition, the bacterial plate counting method and bacteriostatic circle method were used to evaluate the antibacterial activity of films. Results:In the PVA/CMC/GO and PVA/CMC/CuS/GO groups, the surface of the PVA/CMC-based film was smooth and flat whereas the nanosheets composite films were irregularly flaky and convex. The biosafety experiments showed that the PVA/CMC-based film composited with GO or CuS/GO nanosheets at the concentration of 100 μg/mL had good biocompatibility. The results of angiogenesis in vitro showed that the migration ratio of HUVEC cells in the PVA/CMC/CuS/GO group was significantly better than those in the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). In the experiment of tube forming area and length, the PVA/CMC/CuS/GO group was significantly better than the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). The osteogenic differentiation in vitro displayed that the alkaline phosphatase and alizarin red staining of MC3T3-E1 cells in the PVA/CMC/CuS/GO group were significantly better than those in the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). In addition, the fluorescence intensity of immunofluorescence staining in alkaline phosphatase and type Ⅰcollagen on MC3T3-E1 cells, and the mRNA expression levels of osteogenic related genes including alkaline phosphatase, bone morphogenetic protein 2, osteocalcin and osteopontin in the PVA/CMC/CuS/GO group were significantly higher than those in the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). The antibacterial assay showed that the PVA/CMC/CuS/GO group had a significantly greater antibacterial activity and a significantly larger inhibition zone against Gram-positive bacteria and Gram-negative bacteria than the PVA/CMC/GO, PVA/CMC and control groups ( P< 0.001). Conclusions:PVA/CMC films composited with GO or CuS/GO nanosheets demonstrate ideal biocompatibility and antibacterial properties which promote angiogenesis and osteogenic differentiation in vitro. In particular, antibacterial PVA/CMC/CuS/GO composite films with the coupling function of angiogenesis and osteogenesis are expected to provide a new strategy for infectious bone defects.

In vitro cytological comparison of osseointegration properties between biomimetic bone trabecular and regular porous structure / 西安交通大学学报(医学版)

【Objective】 To investigate the effects of biomimetic bone trabecular with the same porosity and pore size and regular porous structure on the adhesion, proliferation, and differentiation of osteoblasts, so as to provide theoretical basis for the improvement of osseointegration performance of titanium alloy implants. 【Methods】 The biomimetic bone trabecular and regular porous structures with the same porosity and pore size were generated by computer-aided software, and then processed into disc-shaped Ti6Al4V scaffolds with a diameter of 10 mm and a height of 3 mm by selective laser melting technology. MC3T3-E1 cells, the precursor cells of mouse osteoblasts in the logarithmic growth phase, were seeded on two kinds of scaffolds and divided into biomimetic bone trabecular group and regular porous structure group. After 3 hours of culture, acridine orange staining and phalloidin /DAPI staining were used to evaluate the number of cell adhesion. After 3 days of culture, the scaffolds were examined by scanning electron microscopy to evaluate the adhesion state of cells. After 1, 3, and 5 days of culture, the scaffolds were taken for CCK8 detection to observe the proliferation of cells. After 7 and 14 days of differentiation, alkaline phosphatase (ALP) activity was detected. After 14 days of differentiation, the expressions of osteogenesis-related genes (ALP, OCN, RUNX2) were detected by RT-PCR. After 30 days of differentiation, the scaffolds were stained with alizarin red and 100 g/L cetylpyridinium chloride was used to dissolve mineralized nodules. Calcium salt deposition was qualitatively and quantitatively detected to evaluate cell differentiation. 【Results】 The results of acridine orange and phalloidin /DAPI staining showed that the biomimetic trabecular Ti6Al4V scaffold adhered to more MC3T3-E1 cells than the regular porous structure, and the cytoskeleton of the former scaffold was more densely distributed. The results of scanning electron microscopy showed that the pseudopodia of MC3T3-E1 cells on the biomimetic bone trabecular Ti6Al4V scaffold were longer and the extension state was better than that of the regular porous structure. CCK8 test showed that the proliferation of MC3T3-E1 cells on the biomimetic trabecular bone titanium alloy scaffold was significantly higher than that on the regular porous structure on the 3rd and 5th day, and the difference gradually increased with the increase of time, with statistical significance (P<0.05). The results of cell differentiation test showed that ALP activity on the bionic trabecular scaffold was higher than that on the regular porous structure (P<0.05). The expressions of osteogenic genes (ALP, OCN, RUNX2) in MC3T3-E1 cells on the biomimetic bone trabecular titanium alloy scaffold were significantly higher than those on the regular porous structure (P<0.05). After 30 days of induction, the amount of calcium salt deposited in the bionic trabecular titanium alloy scaffold was significantly larger than that in the regular porous structure (P<0.05). 【Conclusion】 The biomimetic bone trabecular with a porosity of 65% and an equivalent pore size of 600 μm is more conducive to the adhesion, proliferation and differentiation of mouse osteoblast precursor cells MC3T3-E1 on the titanium alloy scaffold than the regular porous structure with the same porosity and pore size. It is theoretically more conducive to improving the osseointegration performance of titanium alloy implants.

Progress in preparation and application of biomimetic nano carriers for cell membrane / 药学实践杂志

Nanocarriers prepared from organic or inorganic materials are widely used in drug targeting system and diagnosis and treatment of disease. However, there are some problems, such as poor targeting, short circulation time in vivo and improvement in the biocompatibility. Biomimetic nanocarriers has carried out research on the issues, which based on different kinds of cell membrane for the nanocarriers modification, endogenous biofilm improving the biocompatibility of carriers in vivo, more accurate targeting, and even producing immunotherapeutic effect. The principle, method, targeting mechanism and therapeutic effect of biomimetic nano carrier technology of cell membrane have been reviewed in this paper, which provide a new direction for the research of new drug delivery system.

Research progress of cell membrane-coated biomimetic nanoparticle delivery systems for the treatment of lung diseases / 药学学报

Lung is susceptible to external disturbance, resulting in a variety of acute and chronic lung diseases. Functionalized nanoparticles as carriers can carry drugs through multiple biological barriers of lung into lung lesions, but there are some problems such as poor targeting and low therapeutic efficiency. As a drug carrier, membrane-coated biomimetic nanoparticles have the characteristics of immune system escape, active targeting, inflammatory chemotaxis and crossing physiological barriers due to the retention of the characteristics of the source cells. Therefore, it has been widely used in the treatment of lung diseases in recent years. In this review, the application of membrane-coated biomimetic nanoparticles in the treatment of lung diseases in the recent years was summarized and classified. Cell membrane sources include erythrocyte membrane, platelet membrane, macrophage membrane, neutrophil membrane, lung epithelial membrane, lung surfactant, endothelial membrane, cancer cell membrane, bacterial membrane, hybrid membrane and so on. The purpose of this review is to provide a new idea for treating lung diseases with membrane-coated biomimetic nanoparticles.

Preparation and anti-Vibrio vulnificus hemolysin A of macrophage membrane hybrid liposome / 药学实践杂志

Objective To prepare a biomimetic nano carrier macrophage membrane hybrid liposome by heterozygous macrophage membrane and liposome, which could be used for the clearance and toxicity inhibition of Vibrio vulnificus hemolysin A (VvhA). Methods Macrophage membrane was extracted and hybridized with liposome by thin-film evaporation combined extrusion method. The hybridized liposome of macrophage membrane was constructed and characterized. The in vitro detoxification ability of the hybridized vector was evaluated by hemolysis test and cytotoxicity test. The detoxification ability of the vector was evaluated by mouse skin infection model. Results Anti toxoid studies in vivo and in vitro showed that the anti-hemolysis rate of macrophage membrane heterozygous liposomes in vitro reached 97.03%, which could effectively inhibit the skin ulceration in subcutaneous infected mice and make the survival rate of abdominal infected mice reach 80%. Conclusion The constructed macrophage membrane hybrid liposome had high detoxification ability, which could provide a potential solution and research basis for the prevention and treatment of Vibrio vulnificus infection.

Immune cell membrane-based biomimetic nanomedicine for treating cancer metastasis

Metastasis is the leading cause of cancer-related death. Despite extensive treatment, the prognosis for patients with metastatic cancer remains poor. In addition to conventional surgical resection, radiotherapy, immunotherapy, chemotherapy, and targeted therapy, various nanobiomaterials have attracted attention for their enhanced antitumor performance and low off-target effects. However, nanomedicines exhibit certain limitations in clinical applications, such as rapid clearance from the body, low biological stability, and poor targeting ability. Biomimetic methods utilize the natural biomembrane to mimic or hybridize nanoparticles and circumvent some of these limitations. Considering the involvement of immune cells in the tumor microenvironment of the metastatic cascade, biomimetic methods using immune cell membranes have been proposed with unique tumor-homing ability and high biocompatibility. In this review, we explore the impact of immune cells on various processes of tumor metastasis. Furthermore, we summarize the synthesis and applications of immune cell membrane-based nanocarriers increasing therapeutic efficacy against cancer metastases via immune evasion, prolonged circulation, enhanced tumor accumulation, and immunosuppression of the tumor microenvironment. Moreover, we describe the prospects and existing challenges in clinical translation.

Research progress on the role of mitochondrial dysfunction in the occurrence, progression and treatment of periodontitis / 口腔疾病防治

@#Periodontitis is a widespread disease worldwide, with the primary cause of tissue loss being an immune inflammatory response mediated by bacteria. Increasing evidence has revealed a significant correlation between mitochondrial dysfunction and the occurrence and progression of periodontitis. This paper provides a review of current research on the role of mitochondrial dysfunction in the occurrence and development of periodontitis and related therapies from the perspectives of oxidative stress, inflammatory responses, and the regulation of mitochondrial homeostasis. Mitochondria are the main source and target of cellular reactive oxygen species. Mitochondrial dysfunction can generate large amounts of reactive oxygen species, exacerbating local oxidative stress in periodontal tissues and causing cell toxicity and tissue damage. Mitochondria are also the center of cellular inflammatory responses, and the positive feedback loop of inflammation induced by mitochondrial dysfunction may explain the persistent and unresolved nature of periodontitis. Biomaterials loaded with pharmacological agents show potential in restoring mitochondrial function, controlling the development of periodontitis, and promoting periodontal tissue regeneration. However, the key sites of mitochondrial dysfunction in the occurrence and development of periodontitis are not yet fully understood, and the improvement of mitochondrial function in periodontal therapy is still in the experimental stage. Future research efforts should focus on the effect of mitochondrial dysfunction on periodontal cells and explore its specific mechanism in the occurrence and progression of periodontitis in order to provide new insights into the treatment of periodontitis.

Research progress in the application of hybrid cell membrane biomimetic nano-drug delivery system in cancer treatment / 国际生物医学工程杂志

The biomimetic strategy of using the cell membrane-coated nanoparticles can retain the physical and chemical properties of the nanoparticles and show the biological characteristics of the source cell membrane, which can further enhance the role of the nanodrug in tumor treatment. A hybrid cell membrane is the fusion of two or more different types of cell membranes. A hybrid cell membrane can endow nanoparticles with multiple biofunctions derived from the source cells compared with a single cell membrane. Hybrid cell membranes provide a foundation to stimulate extensive research into multifunctional biomimetic nano-drug delivery system (NDDS), which is expected to broaden the application of biomimetic nanotechnology in drug delivery systems. In this review paper, the types of hybrid cell membrane used to construct nano-drug delivery systems, the preparation and characterization methods, and cancer treatment research progress in recent years were reviewed.

Advances in anti-invasive fungal drug delivery systems / 浙江大学学报·医学版

Currently, the first-line drugs for invasive fungal infections (IFI), such as amphotericin B, fluconazole and itraconazole, have drawbacks including poor water solubility, low bioavailability, and severe side effects. Using drug delivery systems is a promising strategy to improve the efficacy and safety of traditional antifungal therapy. Synthetic and biomimetic carriers have greatly facilitated the development of targeted delivery systems for antifungal drugs. Synthetic carrier drug delivery systems, such as liposomes, nanoparticles, polymer micelles, and microspheres, can improve the physicochemical properties of antifungal drugs, prolong their circulation time, enhance targeting capabilities, and reduce toxic side effects. Cell membrane biomimetic drug delivery systems, such as macrophage or red blood cell membrane-coated drug delivery systems, retain the membrane structure of somatic cells and confer various biological functions and specific targeting abilities to the loaded antifungal drugs, exhibiting better biocompatibility and lower toxicity. This article reviews the development of antifungal drug delivery systems and their application in the treatment of IFI, and also discusses the prospects of novel biomimetic carriers in antifungal drug delivery.

Heterologous biomimetic synthesis of active ingredients in traditional Chinese medicine:a new mode for protection and development of traditional Chinese medicine resources / 中国中药杂志

Heterologous biomimetic synthesis of the active ingredients of traditional Chinese medicine(TCM) is a new mode of resource acquisition and has shown great potential in the protection and development of TCM resources. According to synthetic biology and by constructing biomimetic microbial cells and imitating the synthesis of active ingredients in medicinal plants and animals, the key enzymes obtained from medicinal plants and animals are scientifically designed and systematically reconstructed and optimized to realize the heterologous synthesis of the active ingredients in microorganisms. This method ensures an efficient and green acquisition of target products, and also achieves large-scale industrial production, which is conducive to the production of scarce TCM resources. Additiona-lly, the method playes a role in agricultural industrialization, and provides a new option for promoting the green and sustainable deve-lopment of TCM resources. This review systematically summarized the important progress in the heterologous biomimetic synthesis of TCM active ingredients from three research areas: biosynthesis of terpenoids, flavonoids, phenylpropanoids, alkaloids and other active ingredients, key points and difficulties in heterologous biomimetic synthesis, and biomimetic cells with complex TCM ingredients. This study facilitated the application of new generation of biotechnology and theory to the development of TCM.

Research progress in biomimetic nano formulations of biofilms / 中国药科大学学报

@#Biomimetic nano formulations of biofilms have low immunogenicity, high targeting, and good biocompatibility, and can avoid being cleared by the endothelial reticular system, thus with in longer blood circulation time in the body.This article mainly reviews the main types as well as advantages and disadvantages of biomimetic nano formulations of biofilms, including tumor cell membranes, red blood cell membranes, platelet membranes, white blood cell membranes, stem cell membranes, extracellular vesicles (exosomes, microvesicles, and apoptotic bodies), endoplasmic reticulum membranes, and composite biofilms, with also a prospect of the challenges facing biomimetic nano formulations of biofilms and their future development based on their current research status, aiming to provide some insight for further research on biomimetic nano formulations of biofilms.

Research progress of biomimetic nano drug delivery system in nervous system disease / 药学学报

Brain delivery of drugs remains challenging due to the presence of the blood-brain barrier (BBB). With advances in nanotechnology and biotechnology, new possibilities for brain-targeted drug delivery have emerged. Biomimetic nano drug delivery systems with high brain-targeting and BBB-penetrating capabilities, along with good biocompatibility and safety, can enable 'invisible' drug delivery. In this review, five different types of biomimetic strategies are presented and their research progress in central nervous system disorders is reviewed. Finally, the challenges and future prospects for biomimetic nano drug delivery systems in intracerebral drug delivery are summarized.

Hippo pathway-manipulating neutrophil-mimic hybrid nanoparticles for cardiac ischemic injury via modulation of local immunity and cardiac regeneration

The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.

Biomimetic nanomedicines for precise atherosclerosis theranostics

Atherosclerosis (AS) is a leading cause of the life-threatening cardiovascular disease (CVD), creating an urgent need for efficient, biocompatible therapeutics for diagnosis and treatment. Biomimetic nanomedicines (bNMs) are moving closer to fulfilling this need, pushing back the frontier of nano-based drug delivery systems design. This review seeks to outline how these nanomedicines (NMs) might work to diagnose and treat atherosclerosis, to trace the trajectory of their development to date and in the coming years, and to provide a foundation for further discussion about atherosclerotic theranostics.

Biomechanical Environment Regulates Biomimetic Mineralization of Bone Matrix / 医用生物力学

Bone defects have always been an important cause of threat to human health, and artificial biomimetic bone repair replacement materials are currently one of the most effective and feasible solution approaches to treat bone damage. To develop artificial bone biomimetic materials, an in vitro biomimetic mineralization system must be constructed first to study in vitro biomimetic mineralization mechanism of natural bone matrix. Collagen is a template for mineralization, and its properties such as crosslinking degree, diameter, osmotic pressure, and surface charge can all directly affect mineralization progress. The biochemical and mechanical environments in which mineralization occurs are also quite distinct in their effects on mineralization process, particularly noncollagenous proteins and fluid shear stress (FSS). FSS is considered to be the main mechanical stimulation of bone tissues in micro-environment, which is of great significance to bone growth, repair and health maintenance. FSS at different levels and loading regimes has significant effects on transformation of amorphous calcium phosphate to bone apatite, self-assembly and directional alignment of collagen fibrils, and formation of hierarchical intrafibrillar mineralization. In this paper, the factors affecting collagen mineralization and their mechanism were summarized, with focus on regulation of FSS on collagen mineralization, and development direction in future was also prospected.

Experimental Study on Puncture Mechanical Properties of Biomimetic Materials / 医用生物力学

Objective To obtain a more suitable puncture method for venipuncture robot through experiments.Methods By using different puncture speeds and angles for biomimetic materials, the force-time curves by various puncture methods were obtained. Results During puncture process, with the increase of the puncture angle, a smaller puncture force was required. The faster puncture speed would lead to a larger puncture force. Conclusions The 40°-45° puncture angleand the 120-300 mm/min puncture speed should be used for designing the puncture method of venipuncture robot. The results provide references for selecting the puncture angle and speed of the venipuncture robot.

Research advances on antitumor mechanism of NK cells and its application in cancer targeted therapy / 药学学报

Natural killer (NK) cells, as an essential part of innate immunity, can directly identify and kill tumor cells after being activated by the synergistic action of surface inhibitory receptors and activated receptors. It can secrete cytokines to recruit dendritic cells (DCs), induce DCs maturation and enhance adaptive immune response. It can target cancer stem cells (CSCs) and circulating tumor cells (CTCs) to inhibit cancer metastasis. NK cells have a unique inflammatory tendency, which can respond to cytokines and chemokines released from tumor sites and migrate to tumor sites, making them occupy an important advantage in cancer targeted therapy. The research on cancer targeted therapy of NK cells as drug delivery carriers, NK cell membrane-coated biomimetic nanoparticles, and NK cell extracellular vesicles (NKEVs) has attracted more and more attention. The article will focus on the mechanism of NK cells inhibiting cancer, and summarize the research progress of cancer targeted therapy of NK cells.

Progress on active tumor-targeting nano drug delivery systems for improving tumor immunotherapy / 药学学报

In recent years, immunotherapy has made great progress in clinical cancer therapy. However, the poor tumor specificity, low intra-tumoral penetration, and low cellular uptake in the systemic delivery of immunotherapeutic drugs lead to low efficacy and poor safety, limiting the development of immunotherapy. Active tumor-targeting nano drug delivery systems (aNDDS) can enhance the concentration of drugs in target cells through the interaction between surface-conjugated antibodies or ligands and the receptors on target cell membranes, providing a viable strategy for specific and efficient drug delivery. In addition, some specific types of cell membranes with the natural targeting ability have been exploited for the construction of biomimetic nanocarriers to improve the drug delivery efficiency. In view of the many advantages of active tumor-targeting nanocarriers, researchers also have designed a series of aNDDS for promoting antitumor immune responses and proved that they improved the efficacy and safety of immunotherapy. In this review, we summarize the recent progress on aNDDS for improving the tumor immunotherapy and look forward to the main challenges and future directions in this field.

Research progress in the application of polydopamine multifunctional nanocontrast agents in molecular imaging of tumors / 国际生物医学工程杂志

The development of multifunctional nanocontrast agents with high sensitivity, high specificity, and low toxicity so that they can precisely localize tumors and reflect tumor biological information in real time is the core of promoting the development of tumor molecular imaging technology and realizing early and precise tumor diagnosis. Polydopamine (PDA) nanomaterials are bionanomaterials with a structure extremely similar to that of natural melanin. They can be easily fabricated and functionalized, and can achieve controlled assembly of functional molecules such as contrast components and targeting ligands via metal coordination, π-π stacking, electrostatic adsorption, and other methods. They have good biocompatibility and biodegradability, show great potential for clinical translation, and have been widely used in molecular imaging of tumors. In this review paper, the preclinical studies of PDA nanoparticles are reviewed as well as the synthesis methods, functionalized modification, and assembly strategies of PDA nanoparticles and their applications in tumor molecular imaging. The development trends of PDA are also presented to promote their application in the field of tumor molecular imaging.