Advances in Polysaccharides for Cartilage Tissue Engineering Repair: A Review.

Cartilage repair has been a significant challenge in orthopedics that has not yet been fully resolved. Due to the absence of blood vessels and the almost cell-free nature of mature cartilage tissue, the limited ability to repair cartilage has resulted in significant socioeconomic pressures. Polysaccharide materials have recently been widely used for cartilage tissue repair due to their excellent cell loading, biocompatibility, and chemical modifiability. They also provide a suitable microenvironment for cartilage repair and regeneration. In this Review, we summarize the techniques used clinically for cartilage repair, focusing on polysaccharides, polysaccharides for cartilage repair, and the differences between these and other materials. In addition, we summarize the techniques of tissue engineering strategies for cartilage repair and provide an outlook on developing next-generation cartilage repair and regeneration materials from polysaccharides. This Review will provide theoretical guidance for developing polysaccharide-based cartilage repair and regeneration materials with clinical applications for cartilage tissue repair and regeneration.

Chitosan Biguanidine/PVP Antibacterial Coatings for Perishable Fruits.

World hunger is on the rise, yet one-third of food is wasted. It is necessary to develop an effective food preservation method to reduce food waste. This article reports a composite film based on chitosan biguanidine hydrochloride(CBg) and poly (N-vinyl-2-pyrrolidone)(PVP) that can be used as a conformal coating for fresh produce. Due to the strong positive charge of CBg, the film has excellent antibacterial properties. Owing to the hydrogen bonds between CBg and PVP, the film has good flexibility and mechanical properties. In addition, the coating is washable, transparent, and can reduce the evaporation of water. The above characteristics mean the film has broad application prospects in the field of food preservation.

Nanofibrous composite aerogel with multi-bioactive and fluid gating characteristics for promoting diabetic wound healing.

Diabetic wounds are difficult to heal, which increases the difficulty of treatment and aggravates the suffering of patients. Especially its intractable large amount of exudate puts forward more stringent requirements for dressings. The accumulation of excessive exudate would prolong inflammation phase and delay wound healing. To manage wound exudate in time and get through the inflammatory phase smoothly, we developed a Janus nanofibrous aerogel with asymmetric wetting properties. The Janus nanofibrous aerogel has a micropattern obtained from cellular nanofibrous structure, which does not require external force to realize the autonomous, rapid and unidirectional transportation of exudate. Benefiting from its structure and fluid gating characteristics, it can not only absorb high-volume liquid but also effectively prohibit liquid penetration in reverse. Besides, the Janus nanofibrous aerogel has excellent antibacterial and antioxidant properties to synergistically promote wound healing. Experiments in diabetic mice model showed that Janus nanofibrous aerogel can prevent maceration of peri-wound tissue, shorten the inflammation phase, and promote diabetic wound healing. Its good elasticity and easy production characteristics are friendly for clinical application.

Biphasic synthesis of biodegradable urchin-like mesoporous organosilica nanoparticles for enhanced cellular internalization and precision cascaded therapy.

It is widely accepted that a small particle size and rough surface can enhance tumor tissue accumulation and tumor cellular uptake of nanoparticles, respectively. Herein, sub-50 nm urchin-inspired disulfide bond-bridged mesoporous organosilica nanoparticles (UMONs) featured with a spiky surface and glutathione (GSH)-responsive biodegradability were successfully synthesized by a facile one-pot biphasic synthesis strategy for enhanced cellular internalization and tumor accumulation. l-Arginine (LA) is encapsulated into the mesopores of UMONs, whose outer surface is capped with the gatekeeper of ultrasmall gold nanoparticles, i.e., UMONs-LA-Au. On the one hand, the mild acidity-activated uncapping of ultrasmall gold can realize a tumor microenvironment (TME)-responsive release of LA. On the other hand, the unique natural glucose oxidase (GOx)-mimicking catalytic activity of ultrasmall gold can catalyze the decomposition of intratumoral glucose to produce acidic hydrogen peroxide (H2O2) and gluconic acid. Remarkably, these products can not only further facilitate the release of LA, but also catalyze the LA-H2O2 reaction for an increased nitric oxide (NO) yield, which realizes synergistic catalysis-enhanced NO gas therapy for tumor eradication. The judiciously fabricated UMONs-LA-Au present a paradigm of TME-responsive nanoplatforms for both enhanced cellular uptake and tumor-specific precision cascaded therapy, which broadens the range of practical biomedical applications and holds a significant promise for the clinical translation of silica-based nanotheranostics.

Controllable synthesis of versatile mesoporous organosilica nanoparticles as precision cancer theranostics.

Despite the advantages of mesoporous silica nanoparticles (MSNs) in drug delivery, the inherent non-biodegradability seriously impedes the clinical translation of inorganic MSNs, so the current research focus has been turned to mesoporous organosilica nanoparticles (MONs) with higher biocompatibility and easier biodegradability. Recent remarkable advances in silica fabrication chemistry have catalyzed the emergence of a library of MONs with various structures and functions. This review will summarize the latest state-of-the-art studies on the precise control of morphology, structure, framework, particle size and pore size of MONs, which enables the precise synthesis of MONs with suitable engineering for precision stimuli-responsive drug delivery/release, bioimaging and synergistic therapy. Besides, the potential challenges about the future development of MONs are also outlooked with the intention of attracting more researchers to promote the clinical translation of MONs.

Functional DNA-based hydrogel intelligent materials for biomedical applications.

Deoxyribonucleic acid (DNA) nanotechnology is a relevant research field of nano-biotechnology, which has developed rapidly in recent years. Researchers have studied DNA far more than they have studied its genetic characteristics, and now it has evolved into the field of nanomedical materials. A variety of articles based on DNA nanostructures can be obtained by rational design and controllable preparation. In particular, intelligent DNA-based hydrogel materials have attracted significant attention as an essential representative of macro DNA materials. They have shown a wide range of applications, especially in the field of biomedical applications. DNA-based hydrogels have many unique and fascinating properties, such as, excellent biocompatibility, biodegradability, basic programmability, catalytic activities, therapeutic potential, and molecular recognition and bonds. The intelligent DNA hydrogel will undergo abrupt changes in the stimulation of temperature, pH value, ionic strength, and solvent composition. These factors can also be used for applications in intelligent materials that play an essential role in biomedical sciences. To date, intelligent DNA hydrogels have been reported for many applications, including controlled drug delivery, targeted gene therapy, cancer therapy, biosensors, protein production, and 3D cell cultures. However, the large-scale production of intelligent DNA hydrogels has not yet been realized, and the synergistic multifunctional integration has not been explored. This review summarizes the current state of DNA nanostructures, especially the intelligent DNA-based hydrogel materials, and focuses on design and engineering for bio-responsive use and proposes some reasonable prospects for the future development of intelligent DNA-based hydrogel materials.

Cellular Nanofiber Structure with Secretory Activity-Promoting Characteristics for Multicellular Spheroid Formation and Hair Follicle Regeneration.

Multicellular spheroids can mimic the in vivo microenvironment and maintain the unique functions of tissues, which has attracted great attention in tissue engineering. However, the traditional culture microenvironment with structural deficiencies complicates the culture and collection process and tends to lose the function of multicellular spheroids with the increase of cell passage. In order to construct efficient and functional multicellular spheroids, in this study, a chitosan/polyvinyl alcohol nanofiber sponge which has an open-cell cellular structure is obtained. The hair follicle (HF) regeneration model was employed to evaluate HF-inducing ability of dermal papilla (DP) multicellular spheroids which formed on the cellular structure nanofiber sponge. Through structural fine-tuning, the nanofiber sponge has appropriate elasticity for the creation of a three-dimensional dynamic microenvironment to regulate cellular behavior. The cellular structure nanofiber sponge tilts the balance of cell-substratum and cell-cell interactions to a state which is more conducive to the formation of controllable multicellular spheroids in a short time. More importantly, it improves the secretory activity of high-passaged dermal papilla cells and restores their intrinsic properties. Experiments using BALB/c nude mice show that cultured DP multicellular spheroids could effectively enhance HF-inducing ability. This novel system provides a simple and efficient strategy for multicellular spheroid formation and HF regeneration.

A controllable local drug delivery system based on porous fibers for synergistic treatment of melanoma and promoting wound healing.

A dual function system that inhibits tumor growth while promoting wound healing is very necessary for melanoma treatment since tumor killing and skin healing are two complementary and influential processes. Herein, a controllable local drug delivery system based on porous fiber membranes incorporated with CuS nanoparticles is designed for chemo-photothermal synergistic melanoma therapy and promoting wound healing. The porous structure on the fiber surface significantly increases the drug loading capacity of the membrane and the photothermal effect of incorporated CuS nanoparticles is used to control the drug release rate. Benefitting from the chemo-photothermal synergistic therapy, the composite membrane can effectively kill melanoma cells in vitro and inhibit tumor growth in vivo. Furthermore, the membrane can also significantly promote the cutaneous wound healing by providing mechanical support and releasing copper ions. Thus, this work provides new ideas for the development of multifunctional local treatment and postoperative care systems.

Dual Stimuli-Responsive Controlled Release Nanocarrier for Multidrug Resistance Cancer Therapy.

Multidrug resistance of cancer cells is a major obstacle for cancer chemotherapy. Herein, we present a nanocarrier that can release chemotherapeutic agents to induce tumor cell death and generate NO under NIR to overcome multidrug resistance in cancer chemotherapy. Owing to the unique structure of the water channel in this controlled release system for chemotherapeutic agents, the nanocarrier surface is equipped with more active sites to graft NO donor molecules. The released NO performs very well in reversing multidrug resistance by inhibiting P-gp expression. Our findings provide new insight into multidrug resistance cancer therapy and controlled release nanocarriers for multiple drugs.

An indirect ELISA-inspired dual-channel fluorescent immunoassay based on MPA-capped CdTe/ZnS QDs.

To meet the need for high-throughput immunoassays, many multiplex fluorescent immunoassays have been proposed. Most of them need different kinds of fluorescent label indicators during the test. In this work, a novel indirect ELISA-inspired dual-channel fluorescent immunoassay based on 3-mercaptopropionic acid capped CdTe/ZnS quantum dots (QDs) was constructed. The ELISA wells were coated with two kinds of antigen-QD complex. When the primary antibodies were present in a sample, they mediated the binding of a secondary antibody-DNA-gold nanoparticle complex to the antigen-QD complex. Then the gold nanoparticles quenched the fluorescence of the QDs and a decrease in fluorescence intensity was observed. Thus, the amount of primary antibody could be estimated from the decrease of fluorescence intensity. Owing to the wide absorption range and the relatively narrow emission band of the QDs, the dual-channel fluorescent immunoassay system could work at the same excitation wavelength and the emission wavelengths of each channel had no interference. As a result, two different kinds of primary antibody could be detected at the same time in one ELISA well, which simplified the operation and greatly improved the efficiency. Besides, only one type of secondary antibody needs to be added to the prepared microtiter plates, which further simplified the operation during the detection procedure. This dual-channel fluorescent immunoassay system will provide new insights into high-throughput immunodetection. Graphical abstract.

Control of capillary behavior through target-responsive hydrogel permeability alteration for sensitive visual quantitative detection.

DNA hydrogels have received considerable attention in analytical science, however, some limitations still exist in the applications of intelligent hydrogels. In this paper, we describe a way to prepare gel film in a capillary tube based on the thermal reversible principle of DNA hydrogel and the principle of capillary action. Because of the slight change in the internal structure of gel, its permeability can be increased by the addition of some specific targets. The capillary behavior is thus changed due to the different permeability of the hydrogel film. The duration time of the target solution flowing through the capillary tube with a specified length is used to quantify this change. With this proposed method, ultra-trace DNA hydrogel (0.01 µL) is sufficient to realize the sensitive detection of cocaine without the aid of other instruments, which has a low detection limit (1.17 nM) and good selectivity.

Layered nanofiber sponge with an improved capacity for promoting blood coagulation and wound healing.

Effective bleeding control and wound healing are very important and can be life saving. However, traditional wound dressings with structural deficiencies are not effective in controlling bleeding and promoting the regeneration of functional tissues. In this study, a three-dimensional (3D) layered nanofiber sponge was obtained by expanding two-dimensional (2D) nanofiber membranes into the third dimension. This sponge has a layered nanofiber structure, which increases the interfacial interaction between the sponge and blood cells to accelerate hemostasis. Through fine-tuning of structure, the 3D nanofiber sponge acquires properties beneficial to wound healing such as good elasticity and high permeability and fluid absorption ratio. The 3D nanofiber sponges are both highly compressible and resilient, providing tamponade for deep wounds and creating a good 3D dynamic microenvironment to regulate cellular behavior. Further research has demonstrated that the layered nanofiber structure could promote the regeneration of functional dermis and the restoration of differentiated adipocytes during the early repair phase. Experiments using model mice with full-thickness skin defects have shown that the layered nanofiber structure could effectively accelerate wound healing and reduce scar formation. This layered 3D nanofiber sponge design is easy to produce. Due to its excellent wound healing property, this porous nanofiber sponge has great potential for future clinical application as wound dressings.

Encapsulation of Thymol in Biodegradable Nanofiber via Coaxial Eletrospinning and Applications in Fruit Preservation.

The application of the nanofiber film in the field of food preservation was an emerging research direction in recent years. With the functionalization of nanofibers, the quality and safety of food can be better guaranteed. In the present work, thymol as an antibacterial agent was encapsulated into poly(lactide- co-glycolide) to form core-shell nanofibers by coaxial electrospinning. With such a core-shell nanofiber film, thymol can be slowly released to headspace between food and the nanofiber film, inhibiting the growth of bacteria on the surface of food. The morphology and core-shell structure of nanofibers were confirmed by scanning electron microscopy and transmission electron microscopy. The antibacterial and fruit preservation abilities of the nanofiber film were tested on strawberries. Studies have shown that it can effectively inhibit the growth of bacteria, fungi, and yeast and extend the shelf life of fruit. This novel antibacterial packaging material with excellent biocompatibility, biodegradability, and good sustained release performance would have a broad application prospect in the field of food preservation.

Stimuli-Responsive Nanocarrier for Co-delivery of MiR-31 and Doxorubicin To Suppress High MtEF4 Cancer.

Gene interference-based therapeutics represent a fascinating challenge and show enormous potential for cancer treatment, in which microRNA is used to correct abnormal gene. On the basis of the above, we introduced microRNA-31 to bind to 3'-untranslated region of mtEF4, resulting in the downregulation of its messenger RNA and protein to trigger cancer cells apoptosis through mitochondria-related pathway. To achieve better therapeutic effect, a mesoporous silica nanoparticle-based controlled nanoplatform had been developed. This system was fabricated by conjugation of microRNA-31 onto doxorubicin-loaded mesoporous silica nanoparticles with a poly(ethyleneimine)/hyaluronic acid coating, and drug release was triggered by acidic environment of tumors. By feat of surface functionalization and tumor-specific conjugation to nanoparticles, our drug delivery system could promote intracellular accumulation of drugs via the active transport at tumor site. More importantly, microRNA-31 not only directly targeted to mtEF4 to promote cell's death, but had synergistic effects when used in combination with doxorubicin, and achieved excellent superadditive effects. As such, our research might provide new insights toward detecting high mtEF4 cancer and exploiting highly effective anticancer drugs.

Wettability alteration in a functional capillary tube for visual quantitative point of care testing.

Capillarity is an extremely common physical-chemical phenomenon related to wettability in nature, which has wide theoretical and practical interest. Herein, we reported a facile sensing device based on capillary force change in a vertical capillary tube. In this height-based capillary sensor (HCS), the inner surface of the capillary tube was modified with a layer of molecules with wetting responsibility based on the well-known simple surface chemistry. With targets in different concentrations, the wettability of the surface modified with responsive molecules would produce different changes. The responsive surfaces would change the capillary force of the vertical capillary tube, and result in different column heights. Like a thermometer, H+ and phenol have been quantified visually based on the height of the liquid inside the capillary tube.

Wetting transition in nanochannels for biomimetic free-blocking on-demand drug transport.

Water wetting behavior in nanometer dimensions is of great importance to the signal transmission and substance transport of organisms, e.g., aquaporins on cell membranes. A biological channel can control the transport of water and ions by regulating channel wettability, which results from the transition between the intrinsic hydrophobic state and the stimulus-induced hydration state. Inspired by aquaporins in nature, herein, a biomimetic free-blocking on-demand delivery system is proposed, which is constructed by controlling the wettability of the inner surface of nanochannels of mesoporous silica nanoparticles (MSNs). Such a system is completely different from the traditional physically occluding pore controlled release system. It circumvents the use of other extra capping agents, thus overcoming the limitations of the traditional nano "gate" blockage system with inherent instability, poor plugging capability and low biocompatibility. Additionally, further applications in drug delivery have shown that this system can selectively release entrapped drugs in beta cells triggered by intracellular glucose in a controlled manner but not in normal cells. This hydrophobic gating drug delivery system with simple and effective performance provides a new opportunity for constructing a mass transport platform from the perspective of surface wettability.

Free-Blockage Mesoporous Anticancer Nanoparticles Based on ROS-Responsive Wetting Behavior of Nanopores.

To achieve an excellent delivery effect of drug, stimuli-responsive nano "gate" with physical blockage units is usually constructed on the surface of the mesoporous silica nanocarriers (MSNs). In nature, the aquaporins in cell membrane can control the transport of water molecules by regulating the channel wettability, which is resulted from the conformational change of amino acids in the channel. Inspired by this phonomenon, herein a new concept of free-blockage controlled release system is proposed, which is achieved by controlling the wettability of the internal surface of nanopores on MSNs. Such a new system is different from the physical-blockage controlled release system, which bypasses the use of nano "gate" and overcomes the limitations of traditional physical blockage system. Moreover, further studies have shown that the system can selectively release the entrapped doxorubicin in human breast adenocarcinoma (MCF-7) cells triggered by intracellular reactive oxygen species (ROS) but not in normalhuman umbilical vein endothelial cells (HUVECs) containing ROS with low levels. The wettability-determined free-blockage controlled release system is simple and effective, and it can also be triggered by intracellular biological stimuli, which provides a new approach for the future practical application of drug delivery and cancer therapy.

A Voltage-Responsive Free-Blockage Controlled-Release System Based on Hydrophobicity Switching.

Controlled-release systems based on mesoporous silica nanomaterials (MSNs) have drawn great attention owing to their potential biomedical applications. Various switches have been designed to control the release of cargoes through the construction of physical blocking units on the surface of MSNs. However, such physical blockages are limited by poor sealing ability and low biocompatibility, and most of them lack closure ability. Herein, a voltage-responsive controlled-release system was constructed by functionalizing the nanopore of MSNs with ferrocene. The system realized free-blockage controlled release and achieved pulsatile release. The nanopores of the ferrocene-functionalized MSNs were hydrophobic enough to prevent invasion of the solution. Once a suitable voltage was applied, the nanopores became hydrophilic, which was followed by invasion of the solution and the release of the cargos. Moreover, pulsatile release was realized, which avoided unexpected release after the stimulus disappeared. Thus, we believe that our studies provide new insight into highly effective blockage for MSNs. Furthermore, the voltage-responsive release system is expected to find use in electrical stimulation combination therapy and bioelectricity-responsive release.

Voltage-Responsive Controlled Release Film with Cargo Release Self-Monitoring Property Based on Hydrophobicity Switching.

Herein, voltage-responsive controlled release film was constructed by grafting ferrocene on the mesoporous inverse opal photonic crystal (mIOPC). The film achieved free-blockage controlled release and realized the monitoring of cargo release without external indicator. Free-blockage was attributed to the voltage switchable nanovalves which undergo hydrophobic-to-hydrophilic transition when applying voltage. Monitoring of cargo release was attributed to the optical property of mIOPC, the bandgap of mIOPC had a red shift when the solution invaded in. The film was hydrophobic enough to stop solution intrusion. Once the voltage was applied, the film became hydrophilic, leading to invasion of the solution. As a result, the cargos were released and the bandgap of mIOPC was red-shifted. Therefore, in this paper both a free-blockage controlled release film and a release sensing system was prepared. The study provides new insights into highly effective controlled release and release sensing without indicator.

Reverse-Bumpy-Ball-Type-Nanoreactor-Loaded Nylon Membranes as Peroxidase-Mimic Membrane Reactors for a Colorimetric Assay for H2O2.

Herein we report for the first time fabrication of reverse bumpy ball (RBB)-type-nanoreactor-based flexible peroxidase-mimic membrane reactors (MRs). The RBB-type nanoreactors with gold nanoparticles embedded in the inner walls of carbon shells were loaded on nylon membranes through a facile filtration approach. The as-prepared flexible catalytic membrane was studied as a peroxidase-mimic MR. It was found that the obtained peroxidase-mimic MR could exhibit several advantages over natural enzymes, such as facile and good recyclability, long-term stability and easy storage. Moreover, the RBB NS-modified nylon MRs as a peroxidase mimic provide a useful colorimetric assay for H2O2.