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.

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.

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.

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.

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.

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.

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.

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.

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.

Natural self-healing injectable hydrogels loaded with exosomes and berberine for infected wound healing.

Complete and rapid healing of infected skin wounds remains a challenge in current clinical treatment. In this study, we prepared a self-healing injectable CK hydrogel by crosslinking two natural polysaccharides, carboxymethyl chitosan and oxidized konjac glucomannan, based on the Schiff base bond. To enhance the biological function of the hydrogel, we multi-functionalized hydrogen by loading it with berberine (BBR) and stem cell-derived exosomes (Exo), forming a composite hydrogel, CK@BBR&Exo, which could be injected directly into the wound through a needle and adhered to the wound. Furthermore, the self-healing properties of CK@BBR&Exo increased its usefulness and service life. Additionally, the drug-loaded CK@BBR&Exo hydrogel was versatile, inhibiting bacterial growth, regulating the inflammatory response, and promoting neovascularization in infected skin wounds, thus achieving the rapid healing of infected skin wounds. These results suggest that the CK@BBR&Exo-injectable self-healing hydrogel is an ideal dressing for treating infected skin wounds.

Lipopolysaccharides of Brucella suis S2 Impaired the Process of Decidualization in Early Pregnancy in Mice.

Brucellosis is a notorious zoonotic disease caused by Brucella, which can lead to reproductive diseases in humans and animals, such as infertility and abortion. Lipopolysaccharides (LPS) are the main virulence factor of Brucella. LPS derived from Brucella are different and non-classical and are less toxic and less active than LPS isolated from E. coli. However, the effects and possible mechanisms of Brucella LPS-caused pregnancy loss remain to be revealed. In the present study, we investigated the effects of Brucella suis S2 LPS on early pregnancy loss in mice. The results indicated that embryo implantation failure was induced by Brucella LPS treatment in a dose-dependent manner. The injection of Brucella LPS mainly resulted in fibrinolysis in the decidual area of the uterus on the 6th day post coition (dpc), infiltration of large granular cells among the decidual cells near the embryo on the 8th dpc, a large number of gaps in the decidual area, and cell necrosis around the embryo. In addition, the expression of Cyclin D3 mRNA in the uterus on the 7th and 8th dpc and IGFBP-1 mRNA and the progesterone receptor in the uterus on the 6th and 7th dpc were also inhibited. Moreover, the expression of decidualization marker Cyclin D3 and decidualization prolactin-associated protein (dPRP) in endometrial stromal cells were also inhibited by Brucella LPS treatment in vitro. In summary, Brucella LPS affect the process of endometrial decidualization in mice by affecting the structure of the decidua and the expression of decidual marker factors in endometrial stromal cells.

Flourishing tumor organoids: History, emerging technology, and application.

Malignant tumors are one of the leading causes of death which impose an increasingly heavy burden on all countries. Therefore, the establishment of research models that closely resemble original tumor characteristics is crucial to further understanding the mechanisms of malignant tumor development, developing safer and more effective drugs, and formulating personalized treatment plans. Recently, organoids have been widely used in tumor research owing to their advantages including preserving the structure, heterogeneity, and cellular functions of the original tumor, together with the ease of manipulation. This review describes the history and characteristics of tumor organoids and the synergistic combination of three-dimensional (3D) culture approaches for tumor organoids with emerging technologies, including tissue-engineered cell scaffolds, microfluidic devices, 3D bioprinting, rotating wall vessels, and clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR-Cas9). Additionally, the progress in research and the applications in basic and clinical research of tumor organoid models are summarized. This includes studies of the mechanism of tumor development, drug development and screening, precision medicine, immunotherapy, and simulation of the tumor microenvironment. Finally, the existing shortcomings of tumor organoids and possible future directions are discussed.

Biomaterial-based gene therapy.

Gene therapy, a medical approach that involves the correction or replacement of defective and abnormal genes, plays an essential role in the treatment of complex and refractory diseases, such as hereditary diseases, cancer, and rheumatic immune diseases. Nucleic acids alone do not easily enter the target cells due to their easy degradation in vivo and the structure of the target cell membranes. The introduction of genes into biological cells is often dependent on gene delivery vectors, such as adenoviral vectors, which are commonly used in gene therapy. However, traditional viral vectors have strong immunogenicity while also presenting a potential infection risk. Recently, biomaterials have attracted attention for use as efficient gene delivery vehicles, because they can avoid the drawbacks associated with viral vectors. Biomaterials can improve the biological stability of nucleic acids and the efficiency of intracellular gene delivery. This review is focused on biomaterial-based delivery systems in gene therapy and disease treatment. Herein, we review the recent developments and modalities of gene therapy. Additionally, we discuss nucleic acid delivery strategies, with a focus on biomaterial-based gene delivery systems. Furthermore, the current applications of biomaterial-based gene therapy are summarized.

Emerging biomaterials for tumor immunotherapy.

BACKGROUND: The immune system interacts with cancer cells in various intricate ways that can protect the individual from overproliferation of cancer cells; however, these interactions can also lead to malignancy. There has been a dramatic increase in the application of cancer immunotherapy in the last decade. However, low immunogenicity, poor specificity, weak presentation efficiency, and off-target side effects still limit its widespread application. Fortunately, advanced biomaterials effectively contribute immunotherapy and play an important role in cancer treatment, making it a research hotspot in the biomedical field. MAIN BODY: This review discusses immunotherapies and the development of related biomaterials for application in the field. The review first summarizes the various types of tumor immunotherapy applicable in clinical practice as well as their underlying mechanisms. Further, it focuses on the types of biomaterials applied in immunotherapy and related research on metal nanomaterials, silicon nanoparticles, carbon nanotubes, polymer nanoparticles, and cell membrane nanocarriers. Moreover, we introduce the preparation and processing technologies of these biomaterials (liposomes, microspheres, microneedles, and hydrogels) and summarize their mechanisms when applied to tumor immunotherapy. Finally, we discuss future advancements and shortcomings related to the application of biomaterials in tumor immunotherapy. CONCLUSION: Research on biomaterial-based tumor immunotherapy is booming; however, several challenges remain to be overcome to transition from experimental research to clinical application. Biomaterials have been optimized continuously and nanotechnology has achieved continuous progression, ensuring the development of more efficient biomaterials, thereby providing a platform and opportunity for breakthroughs in tumor immunotherapy.

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.

Cell membrane-coated nanomaterials for cancer therapy.

With the development of nanotechnology, nanoparticles have emerged as a delivery carrier for tumor drug therapy, which can improve the therapeutic effect by increasing the stability and solubility and prolonging the half-life of drugs. However, nanoparticles are foreign substances for humans, are easily cleared by the immune system, are less targeted to tumors, and may even be toxic to the body. As a natural biological material, cell membranes have unique biological properties, such as good biocompatibility, strong targeting ability, the ability to evade immune surveillance, and high drug-carrying capacity. In this article, we review cell membrane-coated nanoparticles (CMNPs) and their applications to tumor therapy. First, we briefly describe CMNP characteristics and applications. Second, we present the characteristics and advantages of different cell membranes as well as nanoparticles, provide a brief description of the process of CMNPs, discuss the current status of their application to tumor therapy, summarize their shortcomings for use in cancer therapy, and propose future research directions. This review summarizes the research progress on CMNPs in cancer therapy in recent years and assesses remaining problems, providing scholars with new ideas for future research on CMNPs in tumor therapy.

Functional acellular matrix for tissue repair.

In view of their low immunogenicity, biomimetic internal environment, tissue- and organ-like physicochemical properties, and functionalization potential, decellularized extracellular matrix (dECM) materials attract considerable attention and are widely used in tissue engineering. This review describes the composition of extracellular matrices and their role in stem-cell differentiation, discusses the advantages and disadvantages of existing decellularization techniques, and presents methods for the functionalization and characterization of decellularized scaffolds. In addition, we discuss progress in the use of dECMs for cartilage, skin, nerve, and muscle repair and the transplantation or regeneration of different whole organs (e.g., kidneys, liver, uterus, lungs, and heart), summarize the shortcomings of using dECMs for tissue and organ repair after refunctionalization, and examine the corresponding future prospects. Thus, the present review helps to further systematize the application of functionalized dECMs in tissue/organ transplantation and keep researchers up to date on recent progress in dECM usage.

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.

Current state of knowledge on intelligent-response biological and other macromolecular hydrogels in biomedical engineering: A review.

Because intelligent hydrogels have good biocompatibility, a rapid response, and good degradability as well as a stimulus response mode that is rich, hydrophilic, and similar to the softness and elasticity of living tissue, they have received widespread attention and are widely used in biomedical engineering. In this article, we conduct a systematic review of the use of smart hydrogels in biomedical engineering. First, we introduce the properties and applications of hydrogels and compare the similarities and differences between traditional hydrogels and smart hydrogels. Secondly, we summarize the intelligent hydrogel types, the mechanisms of action used by different hydrogels, and the materials for preparing different types of hydrogels, such as the materials for the preparation of temperature-responsive hydrogels, which mainly include gelatin, carrageenan, agarose, amylose, etc.; summarize the morphologies of different hydrogels, such as films, fibers and microspheres; and summarize the application of smart hydrogels in biomedical engineering, such as for the delivery of proteins, antibiotics, deoxyribonucleic acid, etc. Finally, we summarize the shortcomings of current research and present future prospects for smart hydrogels. The purpose of this paper is to provide researchers engaged in related fields with a systematic review of the application of intelligent hydrogels in biomedical engineering. We hope that they will get some inspiration from this work to provide new directions for the development of related fields.

Current Understanding of Hydrogel for Drug Release and Tissue Engineering.

Due to their good absorption, satisfactory biocompatibility, and high safety, hydrogels have been widely used in the field of biomedicine, including for drug delivery and tissue regeneration. In this review, we introduce the characteristics and crosslinking methods of natural and synthetic hydrogels. Then, we highlight the design and principle of intelligent hydrogels (i.e., responsive hydrogels) used for drug release. Moreover, we introduce the application of the application of hydrogels in drug release and tissue engineering, and the limitations and research directions of hydrogel in drug release and tissue engineering are also considered. We hope that this review can provide a reference for follow-up studies in related fields.