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Azobenzene (Azo) and its derivatives are versatile stimuli-responsive molecules. Their reversible photoisomerization and susceptibility to reduction-mediated cleavage make them valuable for various biomedical applications. Upon exposure to the UV light, Azo units undergo a thermodynamically stable trans-to-cis transition, which can be reversed by heating in the dark or irradiation with visible light. Additionally, the N=N bonds in azobenzenes can be cleaved under hypoxic conditions by azoreductase, making azobenzenes useful as hypoxia-responsive linkers. The integration of azobenzenes into nanomedicines holds promise for enhancing therapeutic efficacy, particularly in tumor targeting and controllable drug release. In this Concept paper, recent advances in the design and applications of azobenzene-based nanomedicines are updated, and future development opportunities are also summarized.

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This study investigates hydrogels based on 2-Acrylamido-2-methyl-1-propanesulfonic acid sodium salt (AMPS) copolymers, incorporating N-hydroxyethyl acrylamide (HEA) and 3-sulfopropyl acrylate potassium salt (SPA). The addition of HEA and SPA is designed to fine-tune the hydrogels' water absorption and mechanical properties, ultimately enhancing their characteristics and expanding their potential for biomedical applications. A copolymer of AMPS, 2-carboxyethyl acrylate (CEA) combined with methacrylic acid (MAA) as poly(AMPS-stat-CEA-stat-MAA, PACM), was preliminarily synthesized. CEA and MAA were modified with allyl glycidyl ether (AGE) through ring-opening, yielding macromers with pendant allyl groups (PACM-AGE). Copolymers poly(AMPS-stat-HEA-stat-CEA-stat-MAA) (PAHCM) and poly(AMPS-stat-SPA-stat-CEA-stat-MAA) (PASCM) were also synthesized and modified with AGE to produce PAHCM-AGE and PASCM-AGE macromers. These copolymers and macromers were characterized by 1H NMR, FT-IR, and GPC, confirming successful synthesis and functionalization. The macromers were then photocrosslinked into hydrogels and evaluated for swelling, water content, and mechanical properties. The results revealed that the PASCM-AGE hydrogels exhibited superior swelling ratios and water retention, achieving equilibrium water content (~92%) within 30 min. While the mechanical properties of HEA and SPA containing hydrogels show significant differences compared to PACM-AGE hydrogel (tensile strength 2.5 MPa, elongation 47%), HEA containing PAHCM-AGE has a higher tensile strength (5.8 MPa) but lower elongation (19%). In contrast, SPA in the PASCM-AGE hydrogels led to both higher tensile strength (3.7 MPa) and greater elongation (92%), allowing for a broader range of hydrogel properties. An initial study on drug delivery behavior was conducted using PACM-AGE hydrogels loaded with photosensitizers, showing effective absorption, release, and antibacterial activity under light exposure. These AMPS-based macromers with HEA and SPA modifications demonstrate enhanced properties, making them promising for wound management and drug delivery applications.

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The abundance of molecules on early Earth likely enabled a wide range of prebiotic chemistry, with peptides playing a key role in the development of early life forms and the evolution of metabolic pathways. Among peptides, those with enzyme-like activities occupy a unique position between peptides and enzymes, combining both structural flexibility and catalytic functionality. However, their full potential remains largely untapped. Further exploration of these enzyme-like peptides at the nanoscale could provide valuable insights into modern nanotechnology, biomedicine, and even the origins of life. Hence, this review introduces the groundbreaking concept of "peptide nanozymes (PepNzymes)", which includes single peptides exhibiting enzyme-like activities, peptide-based nanostructures with enzyme-like activities, and peptide-based nanozymes, thus enabling the investigation of biological phenomena at nanoscale dimensions. Through the rational design of enzyme-like peptides or their assembly with nanostructures and nanozymes, researchers have found or created PepNzymes capable of catalyzing a wide range of reactions. By scrutinizing the interactions between the structures and enzyme-like activities of PepNzymes, we have gained valuable insights into the underlying mechanisms governing enzyme-like activities. Generally, PepNzymes play a crucial role in biological processes by facilitating small-scale enzyme-like reactions, speeding up molecular oxidation-reduction, cleavage, and synthesis reactions, leveraging the functional properties of peptides, and creating a stable microenvironment, among other functions. These discoveries make PepNzymes useful for diagnostics, cellular imaging, antimicrobial therapy, tissue engineering, anti-tumor treatments, and more while pointing out opportunities. Overall, this research provides a significant journey of PepNzymes' potential in various biomedical applications, pushing them towards new advancements.

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Microalgae are microorganisms that are rich in bioactive compounds, including pigments, proteins, lipids, and polysaccharides. These compounds can be utilized for a number of biomedical purposes, including drug delivery, wound healing, and tissue engineering. Nevertheless, encapsulating microalgae cells and microalgae bioactive metabolites is vital to protect them and prevent premature degradation. This also enables the development of intelligent controlled release strategies for the bioactive compounds. This review outlines the most employed encapsulation techniques for microalgae, with a particular focus on their biomedical applications. These include ionic gelation, oil-in-water emulsions, and spray drying. Such techniques have been widely explored, due to their ability to protect sensitive compounds from degradation, enhance their stability, extend their shelf life, mask undesirable tastes or odours, control the release of bioactive compounds, and enable targeted delivery to specific sites within the body or environment. Moreover, a patent landscape analysis is also provided, allowing an overview of the microalgae encapsulation technology development applied to a variety of fields, including pharmaceuticals, cosmetics, food, and agriculture.

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With the accelerating trend of global aging, bone damage caused by orthopedic diseases, such as osteoporosis and fractures, has become a shared international event. Traffic accidents, high-altitude falls, and other incidents are increasing daily, and the demand for bone implant treatment is also growing. Although extensive research has been conducted in the past decade to develop medical implants for bone regeneration and healing of body tissues, due to their low biocompatibility, weak bone integration ability, and high postoperative infection rates, pure titanium alloys, such as Ti-6A1-4V and Ti-6A1-7Nb, although widely used in clinical practice, have poor induction of phosphate deposition and wear resistance, and Ti-Zr alloy exhibits a lack of mechanical stability and processing complexity. In contrast, the Ti-Ni alloy exhibits toxicity and low thermal conductivity. Nonthermal plasma (NTP) has aroused widespread interest in synthesizing and modifying implanted materials. More and more researchers are using plasma to modify target catalysts such as changing the dispersion of active sites, adjusting electronic properties, enhancing metal carrier interactions, and changing their morphology. NTP provides an alternative option for catalysts in the modification processes of oxidation, reduction, etching, coating, and doping, especially for materials that cannot tolerate thermodynamic or thermosensitive reactions. This review will focus on applying NTP technology in bone implant material modification and analyze the overall performance of three common types of bone implant materials, including metals, ceramics, and polymers. The challenges faced by NTP material modification are also discussed.

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Nanozymes, a category of nanomaterials with enzyme-like activity, have garnered growing interest in various biomedical contexts. Notably, nanozymes that are capable of regulating reactive oxygen species levels by emulating antioxidant or prooxidant enzymes within cells hold significant therapeutic potential for a range of disorders. Herein, we overview the catalytic mechanisms of four exemplary nanozymes within the orthopedic domain. Subsequently, we emphasize recent groundbreaking advancements in nanozyme applications in orthopaedics, encompassing osteoarthritis, osteoporosis, intervertebral disc degeneration, bone defects, spinal cord injury, gout, rheumatoid arthritis, osteosarcoma and bone infection. Furthermore, we discuss the emerging area's future prospects and several noteworthy challenges in biomedical application. This review not only fosters the ongoing development of nanozyme research but also fosters the emergence of more potent nanozymes for the treatment of orthopaedical diseases in the future.

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Metal-organic frameworks (MOFs) are composite crystalline materials created through the coordination of metal ions and organic ligands. MOFs have attracted extensive attention in the biomedical field based on the advantages of internal porosity, customizable porosity, and facile surface modification. This review examines the utilization of MOFs in drug delivery systems, focusing on the research progress from the aspects of coloading drug systems, intelligent responsive carriers, biological macromolecule stabilizers, self-driving micro/nanomotors, and multifunctional living carriers. In addition, the current challenges the research faces are also discussed. The review aims to provide a reference for the further application of MOFs as advanced drug delivery systems.

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Background Selenium nanoparticles (SeNPs) are one of the metal nanoparticles that have been widely utilized for their anti-microbial, anti-oxidant, anti-inflammatory activities, and other biomedical applications. Tridax procumbens (TP) stem extract is a promising herb species rich in flavonoids, tannins, alkaloids, phytosterols, and hydroxycinnamates, which play a major role in wound healing applications.  Aim The study aims to synthesize SeNPs using TP stem extract, characterizations, and its biomedical applications. Materials and methods SeNPs were synthesized using TP stem extract. The green synthesis of SeNPs was confirmed by ultraviolet-visible (UV-vis) spectra analysis. The synthesized SeNPs were characterized using Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The agar well diffusion method was utilized to evaluate the anti-bacterial properties of the green synthesized SeNPs using TP stem extract. The anti-oxidant effect of SeNPs was tested using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, ferric-reducing anti-oxidant power assay (FRAP), and hydroxyl radical scavenging assay (H2O2). The anti-inflammatory effect was investigated using the bovine serum albumin assay and egg albumin denaturation method, and the cytotoxic effect of the green synthesized SeNPs was tested using the brine shrimp lethality (BSL) assay. Results The green synthesis of SeNPs was confirmed using different types of analysis techniques. The characterizations were done by UV-visible spectroscopy analysis, exhibiting a maximum peak at the range of 330 nm. SEM analysis revealed the shape of the nanoparticle to be hexagonal. The agar well diffusion method exhibited the anti-bacterial efficacy of SeNPs against wound microorganisms with a zone of inhibition of 14.6 mm for Escherichia coli (E. coli), 15.8 mm for Staphylococcus aureus (S. aureus), and 15.4 mm for Pseudomonas aeruginosa (P. aeruginosa). The TP stem-mediated SeNPs showed potential effects in anti-oxidant, anti-inflammatory, and cytotoxic activity, which shows very little toxicity. Conclusion Overall, the green synthesis of TP-stem-mediated SeNPs has great potential in biomedical applications. Thus, the synthesized SeNPs exhibit significant anti-bacterial efficacy against wound pathogens. The TP stem-mediated SeNPs showed potential effects in anti-oxidant, anti-inflammatory, and cytotoxic activity, which shows low toxicity. Furthermore, the green-synthesized SeNPs can be utilized in therapeutic management.

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Plant fibers are strong, robust, flexible, versatile, renewable, and sustainable, making them valuable for many applications. Fibers from plants are now utilized in biomedical applications as reinforcements for biological composites to enhance the mechanical characteristics of composite biological materials including rigidity, tensile strength, and endurance. Reinforcement composites with hybrid components were explored in biodevices for prospective utilization in orthopedics, prosthetics, tissue fabrication, and surgical dressings. This review presents an overview of plant fibers, including their characteristics, influencing variables, and numerous applications. The text explores several methods for creating synthetic composites using common, sustainable fibers and the distinct characteristics of the resulting biological materials. The text also analyses many instances of composite hybrids and their application in the biological field. The results are summarised and suggestions for potential improvements are presented. The current research primarily examines the concept, specifications, efficiency, and potential advancements of composites with hybrid characteristics made from plant fibers.

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With the development in the field of biomaterials, research on alternative biocompatible materials has been initiated, and alginate in polysaccharides has become one of the research hotspots due to its advantages of biocompatibility, biodegradability and low cost. In recent years, with the further understanding of microscopic molecular structure and properties of alginate, various physicochemical methods of cross-linking strategies, as well as organic and inorganic materials, have led to the development of different properties of alginate hydrogels for greatly expanded applications. In view of the potential application prospects of alginate-based hydrogels, this paper reviews the properties and preparation of alginate-based hydrogels and their major achievements in delivery carrier, dressings, tissue engineering and other applications are also summarized. In addition, the combination of alginate-based hydrogel and new technology such as 3D printing are also involved, which will contribute to further research and exploration.

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The research study aimed to maximize the important medical role of star anise extract (SAE) through its loading on a widely available natural polymer (chitosan, Cs). Thus, SAE loaded chitosan nanoparticles (CsNPs) was prepared. The finding illustrated the formation of spherical particles of SAE loaded CsNPs as proved by transmission electron microscope (TEM). In addition, the average particle size of CsNPs and SAE loaded CsNPs are 131.8 ± 24.63 and 318.5 ± 73.94 nm, respectively. Scanning electron microscope (SEM) showed the presence of many spherical particles deposited on the surface of CsNPs owing to the deposition of SAE on the surface and encapsulated into pores of CsNPs. It also showed the presence of elements such as sodium, potassium, copper, magnesium, zinc, calcium, and iron, as well as the elements that accompanied with CsNPs: carbon, oxygen, nitrogen, and phosphorus. The extract was rich in bioactive components, such as anethole, shikimic acid, and different flavonoids, contributing to its medicinal qualities. The bioactive molecules in SAE were assessed by chromatographic analysis. Using the agar well diffusion test, the antibacterial qualities of CsNPs and SAE loaded CsNPs were evaluated against pathogenic bacteria linked to lung illnesses. The most significant inhibition zones showed that the SAE loaded CsNPs had the most antibacterial activity. The anticancer activity using MTT assay was used in the biological assessments to determine the cytotoxicity against the NCl-H460 lung cancer cell line. The results showed that CsNPs loaded with SAE considerably decreased cell viability in a dose-dependent manner, with the most significant anticancer impact by SAE loaded CsNPs. Furthermore, in vivo tests on lung cancer therapy revealed that when compared to other treatment groups, the SAE loaded CsNPs group showed the greatest reduction in tumor biomarkers and inflammation, as seen by decreased levels of Plasma malondialdehyde (MDA), tumor protein 53 (p53), Tumor necrosis factor-alpha (TNF- alpha), and fibronectin. Results concluded that these thorough characterizations, biological assessments, and antibacterial tests have confirmed the effective integration of SAE into CsNPs. Further, SAE loaded CsNPs could be a suitable option for various biomedical applications in tackling lung cancer and the inactivation of bacterial infection.

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The use of biogenic calcium ions for the source of hydroxyapatite (HAp or HA) are very common and have been being explored extensively. However, it usually results high crystalline HA, due to high reaction and decomposition temperatures. In this study, strontium (Sr2+) doped HA from the golden apple snail shells (Pomacea canaliculate L) was successfully synthesized. It was indicated that Sr ions completely replaced calcium (Ca) ions, increased the lattice constant, and consecutively reduced HA crystallinity. Smaller crystal size and ß-type carbonate (CO32-) ions substitution with Ca/P close to 1.67 molar ratio that mimic bone crystals were observed in Sr-doped HA, with significant increased rate of MC3T3-E1 cells viability and higher IC50 values. It was proven that Sr ions substitution resolved challenges on the use of biogenic sources for HA fabrication. Further in vivo study is needed to continue to valorise the results into real biomedical and clinical applications.

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Metal-organic frameworks (MOFs) are a new variety of solid crystalline porous functional materials. As an extension of inorganic porous materials, it has made important progress in preparation and application. MOFs are widely used in various fields such as gas adsorption storage, drug delivery, sensing, and biological imaging due to their high specific surface area, porosity, adjustable pore size, abundant active sites, and functional modification by introducing groups. In this paper, the types of MOFs are classified, and the synthesis methods and functional modification mechanisms of MOFs materials are summarized. Finally, the application prospects and challenges of metal-organic framework materials in the biomedical field are discussed, hoping to promote their application in multidisciplinary fields.

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Chitin and its deacetylated form, chitosan, have demonstrated remarkable versatility in the realm of biomaterials. Their exceptional biocompatibility, antibacterial properties, pro- and anticoagulant characteristics, robust antioxidant capacity, and anti-inflammatory potential make them highly sought-after in various applications. This review delves into the mechanisms underlying chitin/chitosan's biological activity and provides a comprehensive overview of their derivatives in fields such as tissue engineering, hemostasis, wound healing, drug delivery, and hemoperfusion. However, despite the wealth of studies on chitin/chitosan, there exists a notable trend of homogeneity in research, which could hinder the comprehensive development of these biomaterials. This review, taking a clinician's perspective, identifies current research gaps and medical challenges yet to be addressed, aiming to pave the way for a more sustainable future in chitin/chitosan research and application.

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As nanoscale materials with the function of catalyzing substrates through enzymatic kinetics, nanozymes are regarded as potential alternatives to natural enzymes. Compared to protein-based enzymes, nanozymes exhibit attractive characteristics of low preparation cost, robust activity, flexible performance adjustment, and versatile functionalization. These advantages endow them with wide use from biochemical sensing and environmental remediation to medical theranostics. Especially in biomedical diagnosis, the feature of catalytic signal amplification provided by nanozymes makes them function as emerging labels for the detection of biomarkers and diseases, with rapid developments observed in recent years. To provide a comprehensive overview of recent progress made in this dynamic field, here an overview of biomedical diagnosis enabled by nanozymes is provided. This review first summarizes the synthesis of nanozyme materials and then discusses the main strategies applied to enhance their catalytic activity and specificity. Subsequently, representative utilization of nanozymes combined with biological elements in disease diagnosis is reviewed, including the detection of biomarkers related to metabolic, cardiovascular, nervous, and digestive diseases as well as cancers. Finally, some development trends in nanozyme-enabled biomedical diagnosis are highlighted, and corresponding challenges are also pointed out, aiming to inspire future efforts to further advance this promising field.

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The liver is the most important metabolic organ in the body. While mouse models and cell lines have further deepened our understanding of liver biology and related diseases, they are flawed in replicating key aspects of human liver tissue, particularly its complex structure and metabolic functions. The organoid model represents a major breakthrough in cell biology that revolutionized biomedical research. Organoids are in vitro three-dimensional (3D) physiological structures that recapitulate the morphological and functional characteristics of tissues in vivo, and have significant advantages over traditional cell culture methods. In this review, we discuss the generation strategies and current advances in the field focusing on their application in regenerative medicine, drug discovery and modeling diseases.

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The utilization of extracellular vesicles (EVs) in wound healing has been well-documented. However, the direct administration of free EVs via subcutaneous injection at wound sites may result in the rapid dissipation of bioactive components and diminished therapeutic efficacy. Functionalized hydrogels provide effective protection, as well as ensure the sustained release and bioactivity of EVs during the wound healing process, making them an ideal candidate material for delivering EVs. In this review, we introduce the mechanisms by which EVs accelerate wound healing, and then elaborate on the construction strategies for engineered EVs. Subsequently, we discuss the synthesis strategies and application of hydrogels as delivery systems for the sustained release of EVs to enhance complicated wound healing. Furthermore, in the face of complicated wounds, functionalized hydrogels with specific wound microenvironment regulation capabilities, such as antimicrobial, anti-inflammatory, and immune regulation, used for loading engineered EVs, provide potential approaches to addressing these healing challenges. Ultimately, we deliberate on potential future trajectories and outlooks, offering a fresh viewpoint on the advancement of artificial intelligence (AI)-energized materials and 3D bio-printed multifunctional hydrogel-based engineered EVs delivery dressings for biomedical applications.

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Cyanobacteria are the only prokaryotes capable of performing oxygenic photosynthesis on Earth. Besides their traditional roles serving as primary producers, cyanobacteria also synthesize abundant secondary metabolites including carotenoids, alkaloids, peptides, which have been reported to possess medicinal potentials. More importantly, the advancement of synthetic biology technology has further expanded their potential biomedical applications especially using living/engineered cyanobacteria, providing promising and attractive strategies for future disease treatments. To improve the understanding and to facilitate future applications, this review aims to discuss the current status and future prospects of cyanobacterial-based biomedical engineering. Firstly, specific properties of cyanobacteria related with biomedical applications like their natural products of bioactive compounds and heavy metal adsorption were concluded. Subsequently, based on these properties of cyanobacteria, we discussed the progress of their applications in various disease models like hypoxia microenvironment alleviation, wound healing, drug delivery, and so on. Finally, the future prospects including further exploration of cyanobacteria secondary metabolites, the integration of bioactive compounds synthesized by cyanobacteria in situ with medical diagnosis and treatment, and the optimization of in vivo application were critically presented. The review will promote the studies related with cyanobacteria-based biomedical engineering and its practical application in clinical trials in the future.

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MXenes are two-dimensional (2D) transition metal-based carbides, nitrides, and carbonitrides that are synthesized from its precursor MAX phase. The selective etching of the "A" from the MAX phase yields multi-functional MXenes that hold promise in a wide range of energy-based applications and biomedical applications. Based on its intended application, MXenes are prepared as multilayered sheets, monolayer flakes, and quantum dots. Conventionally, MXenes are prepared using hydrofluoric (HF) acid etching; however, the use of HF impedes its effective use in biomedical applications. This calls for the use of nontoxic HF-free synthesis protocols to prepare MXenes safe for biological use. Therefore, we have discussed a facile process to synthesize biocompatible, HF-free MXene nanosheets and quantum dots.

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Irreversible bone defects resulting from trauma, infection, and degenerative illnesses have emerged as a significant health concern. Structurally and functionally controllable hydrogels made by bone tissue engineering (BTE) have become promising biomaterials. Natural proteins are able to establish connections with autologous proteins through unique biologically active regions. Hydrogels based on proteins can simulate the bone microenvironment and regulate the biological behavior of stem cells in the tissue niche, making them candidates for research related to bone regeneration. This article reviews the biological functions of various natural macromolecular proteins (such as collagen, gelatin, fibrin, and silk fibroin) and highlights their special advantages as hydrogels. Then the latest research trends on cross-linking modified macromolecular protein hydrogels with improved mechanical properties and composite hydrogels loaded with exogenous micromolecular proteins have been discussed. Finally, the applications of protein hydrogels, such as 3D printed hydrogels, microspheres, and injectable hydrogels, were introduced, aiming to provide a reference for the repair of clinical bone defects.

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