preparation-cross-linked-sodium-alginate-microspheres-with-different

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 ...

Zhejiang Shuren University

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

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.

Emerging 3D bioprinting applications in plastic surgery.

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.

Emerging biomaterials for tumor immunotherapy.

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.

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

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.

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

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.

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

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.

Microenvironment Remodeling Self-Healing Hydrogel for Promoting Flap Survival.

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 acid‑zinc 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.

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

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.

Developing hydrogels for gene therapy and tissue engineering.

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.

Advancing Organoid Engineering for Tissue Regeneration and Biofunctional Reconstruction.

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.

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

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.

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

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.

Lanjie Lei

Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province,
Institute of Translational Medicine,
Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Institute of Translational Medicine

Zhejiang Shuren University

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