Hydrogen sulfide responsive nanoplatforms: Novel gas responsive drug delivery carriers for biomedical applications

Hydrogen sulfide(H_(2)S)is a toxic,essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter.These studies have mainly focused on the production and pharmacological side effects caused by H_(2)S.Therefore,effective strategies to remove H_(2)S has become a key research topic.Furthermore,the development of novel nanoplatforms has provided new tools for the targeted removal of H_(2)S.This paper was performed to review the association between H_(2)S anddisease,relatedH_(2)S inhibitory drugs,aswell as H_(2)S responsive nanoplatforms(HRNs).This review first analyzed the role of H_(2)S in multiple tissues and conditions.Second,common drugs used to eliminate H_(2)S,as well as their potential for combination with anticancer agents,were summarized.Not only the existing studies on HRNs,but also the inhibition H_(2)S combined with different therapeutic methods were both sorted out in this review.Furthermore,this review provided in-depth analysis of the potential of HRNs about treatment or detection in detail.Finally,potential challenges of HRNs were proposed.This study demonstrates the excellent potential of HRNs for biomedical applications.

Renewable Polymers in Biomedical Applications:From the Bench to the Market

Polymers from renewable resources have been used for a long time in biomedical applications and found an irreplaceable role in some of them.Their uses have been increasing because of their attractive properties,contributing to the improvement of life quality,mainly in drug release systems and in regenerative medicine.Formulations using natural polymer,nano and microscale particles preparation,composites,blends and chemical modification strategies have been used to improve their properties for clinical application.Although many studies have been carried out with these natural polymers,the way to reach the market is long and only very few of them become commercially available.Vegetable cellulose,bacterial cellulose,chitosan,poly(lactic acid)and starch can be found among the most studied polymers for biological applications,some with several derivatives already established in the market,and others with potential for such.In this scenario this work aims to describe the properties and potential of these renewable polymers for biomedical applications,the routes from the bench to the market,and the perspectives for future developments.

Metal-Organic Framework Nanocarriers for Drug Delivery in Biomedical Applications

Investigation of metal–organic frameworks(MOFs)for biomedical applications has attracted much attention in recent years.MOFs are regarded as a promising class of nanocarriers for drug delivery owing to well-defined structure,ultrahigh surface area and porosity,tunable pore size,and easy chemical functionalization.In this review,the unique properties of MOFs and their advantages as nanocarriers for drug delivery in biomedical applications were discussed in the first section.Then,state-ofthe-art strategies to functionalize MOFs with therapeutic agents were summarized,including surface adsorption,pore encapsulation,covalent binding,and functional molecules as building blocks.In the third section,the most recent biological applications of MOFs for intracellular delivery of drugs,proteins,and nucleic acids,especially aptamers,were presented.Finally,challenges and prospects were comprehensively discussed to provide context for future development of MOFs as efficient drug delivery systems.

3D printing biomimeticmaterials and structures for biomedical applications

Over millions of years of evolution,nature has created organisms with overwhelming performances due to their unique materials and structures,providing us with valuable inspirations for the development of next-generation biomedical devices.As a promising new technology,3D printing enables the fabrication of multiscale,multi-material,and multi-functional threedimensional(3D)biomimetic materials and structures with high precision and great flexibility.The manufacturing challenges of biomedical devices with advanced biomimetic materials and structures for various applications were overcome with the flourishing development of 3D printing technologies.In this paper,the state-of-the-art additive manufacturing of biomimetic materials and structures in the field of biomedical engineering were overviewed.Various kinds of biomedical applications,including implants,lab-on-chip,medicine,microvascular network,and artificial organs and tissues,were respectively discussed.The technical challenges and limitations of biomimetic additive manufacturing in biomedical applications were further investigated,and the potential solutions and intriguing future technological developments of biomimetic 3D printing of biomedical devices were highlighted.

Magnetic Helical Micro-and Nanorobots:Toward Their Biomedical Applications

Magnetic helical micro- and nanorobots can perform 3D navigation in various liquids with a sub- micrometer precision under low-strength rotating magnetic fields （〈 10 rer）. Since magnetic fields with low strengths are harmless to cells and tissues, magnetic helical micro/ nanorobots are promising tools for biomedical applications, such as minimally invasive surgery, cell manipulation and analysis, and targeted therapy. This review provides general information on magnetic helical micro/nanorobots, including their fabrication, motion control, and further functionalization for biomedical applications.

Additive manufacturing of promising heterostructure for biomedical applications

As a new generation of materials/structures,heterostructure is characterized by heterogeneous zones with dramatically different mechanical,physical or chemical properties.This endows heterostructure with unique interfaces,robust architectures,and synergistic effects,making it a promising option as advanced biomaterials for the highly variable anatomy and complex functionalities of individual patients.However,the main challenges of developing heterostructure lie in the control of crystal/phase evolution and the distribution/fraction of components and structures.In recent years,additive manufacturing techniques have attracted increasing attention in developing heterostructure due to the unique flexibility in tailored structures and synthetic multimaterials.This review focuses on the additive manufacturing of heterostructure for biomedical applications.The structural features and functional mechanisms of heterostructure are summarized.The typical material systems of heterostructure,mainly including metals,polymers,ceramics,and their composites,are presented.And the resulting synergistic effects on multiple properties are also systematically discussed in terms of mechanical,biocompatible,biodegradable,antibacterial,biosensitive and magnetostrictive properties.Next,this work outlines the research progress of additive manufacturing employed in developing heterostructure from the aspects of advantages,processes,properties,and applications.This review also highlights the prospective utilization of heterostructure in biomedical fields,with particular attention to bioscaffolds,vasculatures,biosensors and biodetections.Finally,future research directions and breakthroughs of heterostructure are prospected with focus on their more prospective applications in infection prevention and drug delivery.

A review of microwave-induced thermoacoustic imaging:Excitation source,data acquisition system and biomedical applications

Microwave-induced thermoacoustic imaging(TAI)is a noninvasive modality based on the differences in microwave absorption of various biological tissues.TAI has been extensively researched in recent years,and several studies have revealed that TAI possesses advantages such as high resolution,high contrast,high imaging depth and fast imaging speed.In this paper,we reviewed the development of the TAI technique,its excitation source,data acquisition system and biomedical applications.It is believed that TAI has great potential applications in biomedical research and clinical study.

Bacterial nanocellulose production and biomedical applications

Bacterial nanocellulose(BNC)is a homopolymer ofβ-1,4 linked glycose,which is synthesized by Acetobacter using simple culturing methods to allow inexpensive and environmentally friendly small-and large-scale production.Depending on the growth media and types of fermentation methods,ultra-pure cellulose can be obtained with different physio-chemical characteristics.Upon biosynthesis,bacterial cellulose is assembled in the medium into a nanostructured network of glucan polymers that are semitransparent,mechanically highly resistant,but soft and elastic,and with a high capacity to store water and exchange gasses.BNC,generally recognized as safe as well as one of the most biocompatible materials,has been found numerous medical applications in wound dressing,drug delivery systems,and implants of heart valves,blood vessels,tympanic membranes,bones,teeth,cartilages,cornea,and urinary tracts.

Laser additive manufacturing of biodegradable Mg-based alloys for biomedical applications: A review

Metallic implants are widely used in internal fixation of bone fracture in surgical treatment.They are mainly used for providing mechanical support and stability during bone reunion,which usually takes a few months to complete.Conventional implants made of stainless steels,Ti-based alloys and CoCrMo alloys have been widely used for orthopedic reconstruction due to their high strength and high corrosion resistance.Such metallic implants will remain permanently inside the body after implantation,and a second surgery after bone healing is needed because the long-term presence of implant will lead to various problems.An implant removal surgery not only incurs expenditure,but also risk and psychological burden.As a consequence,studies on the development of biodegradable implants,which would degrade and disappear in vivo after bone reunion is completed,have drawn researchers’attention.In this connection,Mg-based alloys have shown great potentials as promising implant materials mainly due to their low density,inherent biocompatibility,biodegradability and mechanical properties close to those of bone.However,the high degradation rate of Mg-based implants in vivo is the biggest hurdle to overcome.Apart from materials selection,a fixation implant is ideally tailor-made in size and shape for an individual case,for best surgical outcomes.Therefore,laser additive manufacturing(LAM),with the advent of sophisticated laser systems and software,is an ideal process to solve these problems.In this paper,we reviewed the progress in LAM of biodegradable Mg-based alloys for biomedical applications.The effect of powder properties and laser processing parameter on the formability and quality was thoroughly discussed.The microstructure,phase constituents and metallurgical defects formed in the LAMed samples were delineated.The mechanical properties,corrosion resistance,biocompatibility and antibacterial properties of the LAMed samples were summarized and compared with samples fabricated by traditional processes.In addition,we have made some suggestions for advancing the knowledge in the LAM of Mg-based alloys for biomedical implants.

Effect of sintering temperature on structure and tribological properties of nanostructured Ti-15Mo alloy for biomedical applications

The effect of sintering temperature(1073?1373 K)on the structural and tribological properties of nanostructured ballmilledβ-type Ti?15Mo samples was investigated.The prepared samples were characterized using various apperatus such as X-ray diffractometer,scanning electron microscope(SEM)and ball-on-plate type oscillating tribometer.Wear tests were conducted under different applied loads(2,8 and 16 N).Structural results showed that the mean pore and crystallite size continuously decreased with increasing sintering temperature to reach the lowest values of 4 nm and 29 nm at 1373 K,respectively.The relative density of the sintered sample at 1373 K was as high as 97.0%.Moreover,a higher sintering temperature resulted in higher relative density,greater hardness and elastic modulus of the sample.It was observed that both the friction coefficient and wear rate were lower in the sample sintered at 1373 K which was attributed to the closed porosity.

CRISPR/Cas9 systems:Delivery technologies and biomedical applications

The emergence of the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)genome-editing system has brought about a significant revolution in the realm of managing human diseases,establishing animal models,and so on.To fully harness the potential of this potent gene-editing tool,ensuring efficient and secure delivery to the target site is paramount.Consequently,developing effective delivery methods for the CRISPR/Cas9 system has become a critical area of research.In this review,we present a comprehensive outline of delivery strategies and discuss their biomedical applications in the CRISPR/Cas9 system.We also provide an indepth analysis of physical,viral vector,and non-viral vector delivery strategies,including plasmid-,mRNA-and protein-based approach.In addition,we illustrate the biomedical applications of the CRISPR/Cas9 system.This review highlights the key factors affecting the delivery process and the current challenges facing the CRISPR/Cas9 system,while also delineating future directions and prospects that could inspire innovative delivery strategies.This review aims to provide new insights and ideas for advancing CRISPR/Cas9-based delivery strategies and to facilitate breakthroughs in biomedical research and therapeutic applications.

Smart Polymers and Coatings Obtained by Ionizing Radiation: Synthesis and Biomedical Applications

Gamma radiation has been shown particularly useful for the functionalization of surfaces with stimuli-responsive polymers. This method involves the formation of active sites (free radicals) onto the polymeric backbone as a result of the exposition to high-energy radiation, in which a proper microenvironment for the reaction among monomer and/or polymer and the active sites takes place, thus leading to propagation which forms side chain grafts. The modification of polymers using high-energy irradiation may be performed by the following methods: direct or simultaneous, pre-irradiation oxidative and pre-irradiation. The most frequent ones correspond to the pre-irradiation oxidative method and the direct one. Radiation-grafting has many advantages over conventional methods considering that it does not require catalyst nor additives to initiate the reaction, and in general, no changes on the mechanical properties with respect to the pristine polymeric matrix are observed. This chapter focused on the synthesis of smart polymers and coatings obtained by the use of gamma radiation. In addition, diverse applications of these materials in the biomedical field are also reported.

A state-of-the-art review of the fabrication and characteristics of titanium and its alloys for biomedical applications

Commercially pure titanium and titanium alloys have been among the most commonly used materials for biomedical applications since the 1950 s.Due to the excellent mechanical tribological properties,corrosion resistance,biocompatibility,and antibacterial properties of titanium,it is getting much attention as a biomaterial for implants.Furthermore,titanium promotes osseointegration without any additional adhesives by physically bonding with the living bone at the implant site.These properties are crucial for producing high-strength metallic alloys for biomedical applications.Titanium alloys are manufactured into the three types ofα,β,andα+β.The scientific and clinical understanding of titanium and its potential applications,especially in the biomedical field,are still in the early stages.This review aims to establish a credible platform for the current and future roles of titanium in biomedicine.We first explore the developmental history of titanium.Then,we review the recent advancement of the utility of titanium in diverse biomedical areas,its functional properties,mechanisms of biocompatibility,host tissue responses,and various relevant antimicrobial strategies.Future research will be directed toward advanced manufacturing technologies,such as powder-based additive manufacturing,electron beam melting and laser melting deposition,as well as analyzing the effects of alloying elements on the biocompatibility,corrosion resistance,and mechanical properties of titanium.Moreover,the role of titania nanotubes in regenerative medicine and nanomedicine applications,such as localized drug delivery system,immunomodulatory agents,antibacterial agents,and hemocompatibility,is investigated,and the paper concludes with the future outlook of titanium alloys as biomaterials.

Magnetic iron oxide nanoparticles: Synthesis and surface coating techniques for biomedical applications

Iron oxide nanoparticles are the most popular magnetic nanoparticles used in biomedical applications due to their low cost, low toxicity, and unique magnetic property. Magnetic iron oxide nanoparticles, including magnetite （Fe304） and maghemite （γ-Fe203）, usually exhibit a superparamagnetic property as their size goes smaller than 20 nm, which are often denoted as superparamagnetic iron oxide nanoparticles （SPIONs） and utilized for drug delivery, diagnosis, therapy, and etc. This review article gives a brief introduction on magnetic iron oxide nanoparticles in terms of their fundamentals of magnetism, magnetic resonance imaging （MRI）, and drug delivery, as well as the synthesis approaches, surface coating, and application examples from recent key literatures. Because the quality and surface chemistry play important roles in biomedical applications, our review focuses on the synthesis approaches and surface modifications of iron oxide nanopar- ticles. We aim to provide a detailed introduction to readers who are new to this field, helping them to choose suitable synthesis methods and to optimize the surface chemistry of iron oxide nanoparticles for their interests.

Development of Flexible Luminous Fabrics for Photodynamic Therapy in Biomedical Applications

Fabrics integrating with side-emitting polymer optical fiber( SE-POF) have great potentials for photodynamic therapy( PDT),which is a form of phototherapy recognized as a treatment strategy that is both minimally invasive and minimally toxic.Preliminary research has been undertaken to develop flexible luminous fabrics( FLF) device for PDT used in biomedical applications. The FLF device consists of SE-POFs, textile substrates,light source( LEDs or laser) with proper wavelength,and optical fiber coupling,etc. Different patterns of the fabrics were designed and fabricated purposely,and the light illumination effect was tested including the light power emitting from the patterned optical fiber fabrics,the stability of the illumination,and the light with different wavelengths. The work contributes to the successful development of an efficient and pain-alleviated illumination device for PDT in biomedical application.

Stimuli-responsive peptide assemblies:Design,self-assembly,modulation,and biomedical applications

Peptide molecules have design flexibility,self-assembly ability,high biocompatibility,good biodegradability,and easy functionalization,which promote their applications as versatile biomaterials for tissue engineering and biomedicine.In addition,the functionalization of self-assembled peptide nanomaterials with other additive components enhances their stimuli-responsive functions,promoting function-specific applications that induced by both internal and external stimulations.In this review,we demonstrate recent advance in the peptide molecular design,self-assembly,functional tailoring,and biomedical applications of peptide-based nanomaterials.The strategies on the design and synthesis of single,dual,and multiple stimuli-responsive peptide-based nanomaterials with various dimensions are analyzed,and the functional regulation of peptide nanomaterials with active components such as metal/metal oxide,DNA/RNA,polysaccharides,photosensitizers,2D materials,and others are discussed.In addition,the designed peptide-based nanomaterials with temperature-,pH-,ion-,light-,enzyme-,and ROS-responsive abilities for drug delivery,bioimaging,cancer therapy,gene therapy,antibacterial,as well as wound healing and dressing applications are presented and discussed.This comprehensive review provides detailed methodologies and advanced techniques on the synthesis of peptide nanomaterials from molecular biology,materials science,and nanotechnology,which will guide and inspire the molecular level design of peptides with specific and multiple functions for function-specific applications.

The age of vanadium-based nanozymes: Synthesis, catalytic mechanisms, regulation and biomedical applications

Nanomaterials with enzyme-mimic(nanozyme) activity have garnered considerable attention as a potential alternative to natural enzymes, thanks to their low preparation cost, high activity, ease of preservation, and unique physicochemical properties. Vanadium(V) is a transition metal that integrates the benefits of valence-richness, low cost, and non-toxicity, making it a desirable candidate for developing a range of emerging nanozymes. In this review, we provide the first systematic summary of recent research progress on V-based nanozymes. First, we summarize the preparation of V-based nanozymes using both top-down and bottom-up synthesis methods. Next, we review the mechanism of V-based nanozymes that mimic the activity of various enzymes. We then discuss methods for regulating V-based nanozyme activity, including morphology, size, valence engineering, defect engineering, external triggering, and surface engineering. Afterward, we outline various biomedical applications, including therapeutic, anti-inflammatory, antibacterial, and biosensing. Finally, we prospect the challenges and countermeasures for V-based nanozymes based on their development. By summarizing recent research progress on V-based nanozymes, we hope to provide useful insights for researchers to further explore their potential applications and overcome their existing challenges.

Biomedical applications of engineered heparin-based materials

Heparin is a negatively charged polysaccharide with various chain lengths and a hydrophilic backbone.Due to its fascinating chemical and physical properties,nontoxicity,biocompatibility,and biodegradability,heparin has been extensively used in different fields of medicine,such as cardiovascular and hematology.This review highlights recent and future advancements in designing materials based on heparin for various biomedical applications.The physicochemical and mechanical properties,biocompatibility,toxicity,and biodegradability of heparin are discussed.In addition,the applications of heparin-based materials in various biomedical fields,such as drug/gene delivery,tissue engineering,cancer therapy,and biosensors,are reviewed.Finally,challenges,opportunities,and future perspectives in preparing heparin-based materials are summarized.

Electrospun nanofibrous membranes meet antibacterial nanomaterials:From preparation strategies to biomedical applications

Electrospun nanofibrous membranes(eNFMs)have been extensively developed for bio-applications due to their structural and compositional similarity to the natural extracellular matrix.However,the emergence of antibiotic resistance in bacterial infections significantly impedes the further development and applications of eNFMs.The development of antibacterial nanomaterials substantially nourishes the engineering design of antibacterial eNFMs for combating bacterial infections without relying on antibiotics.Herein,a comprehensive review of diverse fabrication techniques for incorporating antibacterial nanomaterials into eNFMs is presented,encompassing an exhaustive introduction to various nanomaterials and their bactericidal mechanisms.Furthermore,the latest achievements and breakthroughs in the application of these antibacterial eNFMs in tissue regenerative therapy,mainly focusing on skin,bone,periodontal and tendon tissues regeneration and repair,are systematically summarized and discussed.In particular,for the treatment of skin infection wounds,we highlight the antibiotic-free antibacterial therapy strategies of antibacterial eNFMs,including(i)single model therapies such as metal ion therapy,chemodynamic therapy,photothermal therapy,and photodynamic therapy;and(ii)multimodel therapies involving arbitrary combinations of these single models.Additionally,the limitations,challenges and future opportunities of antibacterial eNFMs in biomedical applications are also discussed.We anticipate that this comprehensive review will provide novel insights for the design and utilization of antibacterial eNFMs in future research.

Oligopeptide Self-Assembly:Mechanisms,Stimuli-Responsiveness,and Biomedical Applications

Oligopeptide self-assembly materials have emerged as a promising class of biomaterials with diverse applications in biomedicine.This review highlights the recent progress in comprehending the selfassembly mechanisms intrinsic to oligopeptides and their behavior in response to specific stimuli.By methodically structuring the amino acid sequence and managing external stimuli such as pH levels,redox conditions,or enzymatic activity,we can exercise unprecedented control over the self-assembly process.By controlling the self-assembly process of oligopeptides,various structures with extraordinary versatility can be obtained,including micelles,nanofibers,and coacervate droplets,each possessing modifiable mechanical and chemical properties.Furthermore,these self-assembled constructs demonstrate immense potential within varied biomedical applications.The stimuli-sensitive nature of oligopeptide assembly materials facilitates timely encapsulation and release of therapeutic cargos,consequently eliciting desired cellular responses.This approach paves the way for more precise tumor targeting,personalized medicinal treatments,and well-regulated drug dispensation.Their innate biocompatibility and proficiency in replicating the extracellular matrix(ECM)render them ideally suited for applications such as tissue engineering,wound remediation,and regenerative medicine.In summary,oligopeptide self-assembling materials show tremendous potential as adaptable platforms for cutting-edge biomedical applications,thereby bridging the divide between fundamental research and practical clinical application.