Manganese-derived biomaterials for tumor diagnosis and therapy.

Manganese (Mn) is widely recognized owing to its low cost, non-toxic nature, and versatile oxidation states, leading to the emergence of various Mn-based nanomaterials with applications across diverse fields, particularly in tumor diagnosis and therapy. Systematic reviews specifically addressing the tumor diagnosis and therapy aspects of Mn-derived biomaterials are lacking. This review comprehensively explores the physicochemical characteristics and synthesis methods of Mn-derived biomaterials, emphasizing their role in tumor diagnostics, including magnetic resonance imaging, photoacoustic and photothermal imaging, ultrasound imaging, multimodal imaging, and biodetection. Moreover, the advantages of Mn-based materials in tumor treatment applications are discussed, including drug delivery, tumor microenvironment regulation, synergistic photothermal, photodynamic, and chemodynamic therapies, tumor immunotherapy, and imaging-guided therapy. The review concludes by providing insights into the current landscape and future directions for Mn-driven advancements in the field, serving as a comprehensive resource for researchers and clinicians.

Exosome-based delivery strategies for tumor therapy: an update on modification, loading, and clinical application.

Malignancy is a major public health problem and among the leading lethal diseases worldwide. Although the current tumor treatment methods have therapeutic effect to a certain extent, they still have some shortcomings such as poor water solubility, short half-life, local and systemic toxicity. Therefore, how to deliver therapeutic agent so as to realize safe and effective anti-tumor therapy become a problem urgently to be solved in this field. As a medium of information exchange and material transport between cells, exosomes are considered to be a promising drug delivery carrier due to their nano-size, good biocompatibility, natural targeting, and easy modification. In this review, we summarize recent advances in the isolation, identification, drug loading, and modification of exosomes as drug carriers for tumor therapy alongside their application in tumor therapy. Basic knowledge of exosomes, such as their biogenesis, sources, and characterization methods, is also introduced herein. In addition, challenges related to the use of exosomes as drug delivery vehicles are discussed, along with future trends. This review provides a scientific basis for the application of exosome delivery systems in oncological therapy.

Nanomaterials-assisted gene editing and synthetic biology for optimizing the treatment of pulmonary diseases.

The use of nanomaterials in gene editing and synthetic biology has emerged as a pivotal strategy in the pursuit of refined treatment methodologies for pulmonary disorders. This review discusses the utilization of nanomaterial-assisted gene editing tools and synthetic biology techniques to promote the development of more precise and efficient treatments for pulmonary diseases. First, we briefly outline the characterization of the respiratory system and succinctly describe the principal applications of diverse nanomaterials in lung ailment treatment. Second, we elaborate on gene-editing tools, their configurations, and assorted delivery methods, while delving into the present state of nanomaterial-facilitated gene-editing interventions for a spectrum of pulmonary diseases. Subsequently, we briefly expound on synthetic biology and its deployment in biomedicine, focusing on research advances in the diagnosis and treatment of pulmonary conditions against the backdrop of the coronavirus disease 2019 pandemic. Finally, we summarize the extant lacunae in current research and delineate prospects for advancement in this domain. This holistic approach augments the development of pioneering solutions in lung disease treatment, thereby endowing patients with more efficacious and personalized therapeutic alternatives.

Developing hydrogels for gene therapy and tissue engineering.

Hydrogels are a class of highly absorbent and easily modified polymer materials suitable for use as slow-release carriers for drugs. Gene therapy is highly specific and can overcome the limitations of traditional tissue engineering techniques and has significant advantages in tissue repair. However, therapeutic genes are often affected by cellular barriers and enzyme sensitivity, and carrier loading of therapeutic genes is essential. Therapeutic gene hydrogels can well overcome these difficulties. Moreover, gene-therapeutic hydrogels have made considerable progress. This review summarizes the recent research on carrier gene hydrogels for the treatment of tissue damage through a summary of the most current research frontiers. We initially introduce the classification of hydrogels and their cross-linking methods, followed by a detailed overview of the types and modifications of therapeutic genes, a detailed discussion on the loading of therapeutic genes in hydrogels and their characterization features, a summary of the design of hydrogels for therapeutic gene release, and an overview of their applications in tissue engineering. Finally, we provide comments and look forward to the shortcomings and future directions of hydrogels for gene therapy. We hope that this article will provide researchers in related fields with more comprehensive and systematic strategies for tissue engineering repair and further promote the development of the field of hydrogels for gene therapy.

Role of endoplasmic reticulum stress in lipopolysaccharide-inhibited mouse granulosa cell estradiol production.

The decrease in the level of estradiol (E2) in granulosa cells caused by lipopolysaccharide (LPS) is one of the major causes of infertility underlying postpartum uterine infections; the precise molecular mechanism of which remains elusive. This study investigated the role of endoplasmic reticulum (ER) stress in LPS-induced E2 decrease in mouse granulosa cells. Our results showed that LPS increased the pro-inflammatory cytokines [(interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor (TNF)-α)], activated ER stress marker protein expression [(glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP)], and decreased cytochrome P450 family 19 subfamily A member 1 (Cyp19a1) expression and E2 production. Moreover, inhibition of ER stress by 4-phenylbutyrate (4-PBA) attenuated thapsigargin-(TG, ER stress agonist) or LPS-induced reduction of Cyp19a1 and E2, pro-inflammatory cytokines expression (IL-1ß, IL-6, IL-8, and TNF-α), and the expression of CHOP and GRP78. Additionally, inhibition of toll-like receptor 4 (TLR4) by resatorvid (TAK-242) reversed the inhibitory effects of LPS on Cyp19a1 expression and E2 production, activation of GRP78 and CHOP, and expression of IL-1ß, IL-6, IL-8, and TNF-α. In summary, our study suggests that ER stress is involved in LPS-inhibited E2 production in mouse granulosa cells.

Lycium barbarum polysaccharide enhances development of previously-cryopreserved murine two-cell embryos via restoration of mitochondrial function and down-regulated generation of reactive oxygen species.

Lycium barbarum polysaccharide (LBP) exhibits multiple pharmacological and biological effects, including displaying antioxidant and cytoprotective properties. The current study investigated the effects of LBP-supplemented culture medium on mitochondrial distribution, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) production, mitochondrial deoxyribonucleic acid (mtDNA) copy number, reactive oxygen species (ROS) accumulation, and development of previously-cryopreserved murine two-cell embryos. Results indicate that LBP enhances development of such embryos, and that potential mechanisms include: (1) mitochondrial function enhancement via altering mitochondrial distribution and increasing MMP, ATP production, mtDNA copy number, and expression of genes involved in mitochondrial biogenesis and energy metabolism (NAD-dependent deacetyltransferase sirtuin-1 (SIRT1) and phosphorylated adenosine monophosphate-activated protein kinase (pAMPK)); (2) down-regulation of ROS generation and enhanced expression of the antioxidant genes glutathione peroxidase 4 (GPX4) and superoxide dismutase 1 (SOD1), thereby increasing embryo oxidative stress tolerance; and (3) increased expression of B-cell lymphoma-2 (BCL2), a critical gene for cell survival and embryo development. These results demonstrate that LBP improves development of previously-cryopreserved murine two-cell embryos via restoration of mitochondrial function and down-regulated generation of ROS.

Lycium barbarum polysaccharide improves the development of mouse oocytes vitrified at the germinal vesicle stage.

The cryopreservation of cumulus oocyte complexes (COCs) is an important process in reproductive medicine. However, this process slows both embryo and offspring development. In this study, the effects of maturation medium supplementation with lycium barbarum polysaccharide (LBP) on the developmental competence of vitrified-warmed mouse COCs and the possible mechanisms facilitating this process were investigated. The addition of LBP to the maturation medium improved the maturation rate and enhanced the developmental competence of vitrified-warmed mouse COCs. This may reduce endoplasmic reticulum stress (ERS), preventing cell death and activating both PI3K/AKT and MAPK3/1. In conclusion, cryopreservation lowers the maturation rate and developmental competence of COCs, which can be ameliorated by the application of LBP after warming during maturation.

IRS2 depletion inhibits cell proliferation and decreases hormone secretion in mouse granulosa cells.

Insulin receptor substrate 2 (IRS2) is a component of the insulin/insulin-like growth factor 1 (IGF1) signaling cascade, which plays an important role in mouse hypothalamic and ovarian functions. The present study was conducted to investigate the role of IRS2 in steroidogenesis, apoptosis, cell cycle and proliferation in mouse granulosa cells (GCs). Flow cytometry and CCK8 assay showed that IRS2 knockdown inhibited cell proliferation, reduced cell viability, and increased apoptosis in GCs. The study also revealed that the expression of Cyclin A1, Cyclin B1 and Bcl2 was downregulated, while the expression of Bax, Cyclin D1 and Cyclin D2 was upregulated. ELISA analysis showed that IRS2 knockdown decreased the concentrations of estradiol (E2) and progesterone (P4), which was further validated by the decreased expression of Star, Cyp11a1, and Cyp19a1. Moreover, IRS2 knockdown altered the expression of Has2 and Ptgs2, which are essential for folliculogenesis. In addition, we found that IRS2-mediated cell viability and hormone secretion are dependent on the PI3K/AKT signaling pathway. Collectively, this study demonstrated that IRS2 plays an important role in the regulation of cell proliferation and steroidogenesis in mouse GCs via the PI3K/AKT signaling pathway.

Endoplasmic Reticulum Stress Cooperates in Zearalenone-Induced Cell Death of RAW 264.7 Macrophages.

Zearalenone (ZEA) is a fungal mycotoxin that causes cell apoptosis and necrosis. However, little is known about the molecular mechanisms of ZEA toxicity. The objective of this study was to explore the effects of ZEA on the proliferation and apoptosis of RAW 264.7 macrophages and to uncover the signaling pathway underlying the cytotoxicity of ZEA in RAW 264.7 macrophages. This study demonstrates that the endoplasmic reticulum (ER) stress pathway cooperated in ZEA-induced cell death of the RAW 264.7 macrophages. Our results show that ZEA treatment reduced the viability of RAW 264.7 macrophages in a dose- and time-dependent manner as shown by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay (MTT) and flow cytometry assay. Western blots analysis revealed that ZEA increased the expression of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP), two ER stress-related marker genes. Furthermore, treating the cells with the ER stress inhibitors 4-phenylbutyrate (4-PBA) or knocking down CHOP, using lentivirus encoded short hairpin interfering RNAs (shRNAs), significantly diminished the ZEA-induced increases in GRP78 and CHOP, and cell death. In summary, our results suggest that ZEA induces the apoptosis and necrosis of RAW 264.7 macrophages in a dose- and time-dependent manner via the ER stress pathway in which the activation of CHOP plays a critical role.

Microfluidic Chip Fabrication for Tumor Cell 3D Culture Based on Microwell Arrays.

Compared with traditional 2D cell culture, 3D cell culture more closely resembles the original state of cells in vivo and enables the establishment of in vivo-like microenvironments and cell-cell interactions, thereby providing valuable cellular materials for numerous studies. The direct establishment of in vitro patient tumor models can enhance drug testing, cancer research, and individualized precision therapy. In this study, we propose a microfluidic chip based on microwell arrays for 3D tumor cell culture. This chip combines nanoscale channels and microwell arrays to precisely control cell distribution and nutrient diffusion, thus closely mimicking the tumor microenvironment. The incorporation of microwell arrays allows for simple and rapid high-throughput preparation of tumor spheroids, while promoting the formation of cell-cell and cell-matrix interactions, ultimately enhancing cell viability and function. Preliminary experiments using tumor cell lines validate the ability of the chip to support 3D tumor growth with enhanced physiological relevance. The microfluidic chip serves as a reliable and scalable platform for studying tumor biology and evaluating therapeutic efficacy and is anticipated to expedite cancer research and drug discovery.

Advancing Organoid Engineering for Tissue Regeneration and Biofunctional Reconstruction.

Tissue damage and functional abnormalities in organs have become a considerable clinical challenge. Organoids are often applied as disease models and in drug discovery and screening. Indeed, several studies have shown that organoids are an important strategy for achieving tissue repair and biofunction reconstruction. In contrast to established stem cell therapies, organoids have high clinical relevance. However, conventional approaches have limited the application of organoids in clinical regenerative medicine. Engineered organoids might have the capacity to overcome these challenges. Bioengineering-a multidisciplinary field that applies engineering principles to biomedicine-has bridged the gap between engineering and medicine to promote human health. More specifically, bioengineering principles have been applied to organoids to accelerate their clinical translation. In this review, beginning with the basic concepts of organoids, we describe strategies for cultivating engineered organoids and discuss the multiple engineering modes to create conditions for breakthroughs in organoid research. Subsequently, studies on the application of engineered organoids in biofunction reconstruction and tissue repair are presented. Finally, we highlight the limitations and challenges hindering the utilization of engineered organoids in clinical applications. Future research will focus on cultivating engineered organoids using advanced bioengineering tools for personalized tissue repair and biofunction reconstruction.

Preparation of Cross-Linked Sodium Alginate Microspheres with Different Metal Ions Using the Microfluidic Electrospray Technology.

Microspheres are micrometer-sized particles that can load and gradually release drugs via physical encapsulation or adsorption onto the surface and within polymers. In the field of biomedicine, hydrogel microspheres have been extensively studied for their application as drug carriers owing to their ability to reduce the frequency of drug administration, minimize side effects, and improve patient compliance. Sodium alginate (ALG) is a naturally occurring linear polysaccharide with three backbone glycosidic linkages. There are two auxiliary hydroxyl groups present in each of the moieties of the polymer, which have the characteristics of an alcohol hydroxyl moiety. The synthetic ALG units can undergo chemical cross-linking reactions with metal ions, forming a cross-linked network structure of polymer stacks, ultimately forming a hydrogel. Hydrogel microspheres can be prepared using a simple process involving the ionic cross-linking properties of ALG. In this study, we prepared ALG-based hydrogel microspheres (ALGMS) using a microfluidic electrodeposition strategy. The prepared hydrogel microspheres were uniformly sized and well-dispersed, owing to accurate control of the microfluidic electrospray flow. ALGMS cross-linked with different metal ions were prepared using a microfluidic electrospray technique combining microfluidic and high electric field, and its antimicrobial properties, slow drug release ability, and biocompatibility were investigated. This technology holds promise for application in advanced drug development and production.

The role of cells and their derivatives in otorhinolaryngologic diseases treatment.

Otolaryngology is an important specialty in the field of surgery that deals with the diagnosis and treatment of the ear, nose, throat, trachea, as well as related anatomical structures. Various otolaryngological disorders are difficult to treat using established pharmacological and surgical approaches. The advent of molecular and cellular therapies led to further progress in this respect. This article reviews the therapeutic strategies of using stem cells, immune cells, and chondrocytes in otorhinolaryngology. As the most widely recognized cell derivatives, exosomes were also systematically reviewed for their therapeutic potential in head and neck cancer, otitis media, and allergic rhinitis. Finally, we summarize the limitations of stem cells, chondrocytes, and exosomes, as well as possible solutions, and provide an outlook on the future direction of cell- and derivative-based therapies in otorhinolaryngology, to offer a theoretical foundation for the clinical translation of this therapeutic modality.

Exosomes-carried curcumin based on polysaccharide hydrogel promote flap survival.

Flap grafting is a common technique used to repair skin defects in orthopedics and plastic and reconstructive surgeries. However, oxidative stress injury caused by ischemia and ischemia-reperfusion injury at the distal end of the skin flap can cause flap necrosis. Curcumin is a natural compound with anti-inflammatory and antioxidant properties that tackle oxidative stress. However, its applicability is limited by its poor water solubility. Exosomes are membranous vesicles that can be loaded with hydrophobic drugs. They are widely studied in drug delivery applications and can be investigated to augment curcumin efficiency. In this study, a self-healing oxidized pullulan polysaccharide-carboxymethylated chitosan composite hydrogel was used as a curcumin-loaded exosome delivery system to evaluate its impact on the viability of skin flaps. The hydrogel exhibited good self-healing properties that allowed the continuous and stable release of drugs. It had anti-inflammatory and antioxidant properties that could reduce oxidative stress damage due to early ischemia and hypoxia of the skin flap in vitro. Moreover, this composite hydrogel attenuated inflammatory responses, promoted angiogenesis, and reduced the distal necrosis of the flap in vivo. Therefore, our hydrogel provides a novel strategy for skin flap graft protection with reduced necrosis and the potential for broad clinical applications.

Microenvironment Remodeling Self-Healing Hydrogel for Promoting Flap Survival.

Random flap grafting is a routine procedure used in plastic and reconstructive surgery to repair and reconstruct large tissue defects. Flap necrosis is primarily caused by ischemia-reperfusion injury and inadequate blood supply to the distal flap. Ischemia-reperfusion injury leads to the production of excessive reactive oxygen species, creating a pathological microenvironment that impairs cellular function and angiogenesis. In this study, we developed a microenvironment remodeling self-healing hydrogel [laminarin-chitosan-based hydrogel-loaded extracellular vesicles and ceria nanozymes (LCH@EVs&CNZs)] to improve the flap microenvironment and synergistically promote flap regeneration and survival. The natural self-healing hydrogel (LCH) was created by the oxidation laminarin and carboxymethylated chitosan via a Schiff base reaction. We loaded this hydrogel with CNZs and EVs. CNZs are a class of nanomaterials with enzymatic activity known for their strong scavenging capacity for reactive oxygen species, thus alleviating oxidative stress. EVs are cell-secreted vesicular structures containing thousands of bioactive substances that can promote cell proliferation, migration, differentiation, and angiogenesis. The constructed LCH@EVs&CNZs demonstrated a robust capacity for scavenging excess reactive oxygen species, thereby conferring cellular protection in oxidative stress environments. Moreover, these constructs notably enhance cell migration and angiogenesis. Our results demonstrate that LCH@EVs&CNZs effectively remodel the pathological skin flap microenvironment and marked improve flap survival. This approach introduces a new therapeutic strategy combining microenvironmental remodeling with EV therapy, which holds promise for promoting flap survival.

Nanosphere-reinforced polysaccharide self-healing hydrogels for infected wound healing.

Bacterial infection remarkably impedes wound healing, with antibiotics traditionally serving as the primary therapeutic intervention. However, the escalating misuse of antibiotics and the emergence of bacterial resistance present substantial treatment challenges for infected wounds. Consequently, the development of antibiotic-free antimicrobial dressings holds pertinent research and clinical relevance. To this end, this study aimed to introduce an all-natural hydrogel dressing, amalgamating polyphenols and polysaccharides, exhibiting pronounced antibacterial and antioxidant properties without relying on antibiotics. First, we constructed curcumin-tannic acid­zinc ion nanospheres (CTZN) through self-assembly. Our experimental results showed that the nanospheres had excellent biocompatibility, antioxidant, and antimicrobial abilities. Subsequently, we prepared carboxymethylated chitosan/oxidized sodium alginate hydrogels via Schiff base reactions. Incorporation of CTZN into the hydrogel system not only improves the inherent qualities of the hydrogel but also confers multifunctional properties, including antimicrobial, antioxidant, and anti-inflammatory abilities. In this study, we enhanced the physicochemical properties and biological activity of hydrogels by introducing natural material nanospheres, offering a novel approach that could pave the way for the development of purely natural biomaterial dressings.

Biomaterial-Based CRISPR/Cas9 Delivery Systems for Tumor Treatment.

CRISPR/Cas9 gene editing technology is characterized by high specificity and efficiency, and has been applied to the treatment of human diseases, especially tumors involving multiple genetic modifications. However, the clinical application of CRISPR/Cas9 still faces some major challenges, the most urgent of which is the development of optimized delivery vectors. Biomaterials are currently the best choice for use in CRISPR/Cas9 delivery vectors owing to their tunability, biocompatibility, and efficiency. As research on biomaterial vectors continues to progress, hope for the application of the CRISPR/Cas9 system for clinical oncology therapy builds. In this review, we first detail the CRISPR/Cas9 system and its potential applications in tumor therapy. Then, we introduce the different delivery forms and compare the physical, viral, and non-viral vectors. In addition, we analyze the characteristics of different types of biomaterial vectors. We further review recent research progress in the use of biomaterials as vectors for CRISPR/Cas9 delivery to treat specific tumors. Finally, we summarize the shortcomings and prospects of biomaterial-based CRISPR/Cas9 delivery systems.

Pulmonary inhalation for disease treatment: Basic research and clinical translations.

Pulmonary drug delivery has the advantages of being rapid, efficient, and well-targeted, with few systemic side effects. In addition, it is non-invasive and has good patient compliance, making it a highly promising drug delivery mode. However, there have been limited studies on drug delivery via pulmonary inhalation compared with oral and intravenous modes. This paper summarizes the basic research and clinical translation of pulmonary inhalation drug delivery for the treatment of diseases and provides insights into the latest advances in pulmonary drug delivery. The paper discusses the processing methods for pulmonary drug delivery, drug carriers (with a focus on various types of nanoparticles), delivery devices, and applications in pulmonary diseases and treatment of systemic diseases (e.g., COVID-19, inhaled vaccines, diagnosis of the diseases, and diabetes mellitus) with an updated summary of recent research advances. Furthermore, this paper describes the applications and recent progress in pulmonary drug delivery for lung diseases and expands the use of pulmonary drugs for other systemic diseases.

Emerging 3D bioprinting applications in plastic surgery.

Plastic surgery is a discipline that uses surgical methods or tissue transplantation to repair, reconstruct and beautify the defects and deformities of human tissues and organs. Three-dimensional (3D) bioprinting has gained widespread attention because it enables fine customization of the implants in the patient's surgical area preoperatively while avoiding some of the adverse reactions and complications of traditional surgical approaches. In this paper, we review the recent research advances in the application of 3D bioprinting in plastic surgery. We first introduce the printing process and basic principles of 3D bioprinting technology, revealing the advantages and disadvantages of different bioprinting technologies. Then, we describe the currently available bioprinting materials, and dissect the rationale for special dynamic 3D bioprinting (4D bioprinting) that is achieved by varying the combination strategy of bioprinting materials. Later, we focus on the viable clinical applications and effects of 3D bioprinting in plastic surgery. Finally, we summarize and discuss the challenges and prospects for the application of 3D bioprinting in plastic surgery. We believe that this review can contribute to further development of 3D bioprinting in plastic surgery and provide lessons for related research.

Assembly of Reusable DNA Blocks for Data Storage Using the Principle of Movable Type Printing.

Due to its high coding density and longevity, DNA is a compelling data storage alternative. However, current DNA data storage systems rely on the de novo synthesis of enormous DNA molecules, resulting in low data editability, high synthesis costs, and restrictions on further applications. Here, we demonstrate the programmable assembly of reusable DNA blocks for versatile data storage using the ancient movable type printing principle. Digital data are first encoded into nucleotide sequences in DNA hairpins, which are then synthesized and immobilized on solid beads as modular DNA blocks. Using DNA polymerase-catalyzed primer exchange reaction, data can be continuously replicated from hairpins on DNA blocks and attached to a primer in tandem to produce new information. The assembly of DNA blocks is highly programmable, producing various data by reusing a finite number of DNA blocks and reducing synthesis costs (∼1718 versus 3000 to 30,000 US$ per megabyte using conventional methods). We demonstrate the flexible assembly of texts, images, and random numbers using DNA blocks and the integration with DNA logic circuits to manipulate data synthesis. This work suggests a flexible paradigm by recombining already synthesized DNA to build cost-effective and intelligent DNA data storage systems.