Biosensing of Cysteine through the Induction of Oxygen Vacancies in a Cu/Zr Heterostructure Prepared by Supercritical Antisolvent Technique.

There has been a growing emphasis on facile preparation of binary heterogeneous composite materials. Leveraging the eco-friendly efficiency of supercritical CO2 technology, we achieved precise control over the influencing factors of mass transfer, enabling the accurate modulation of the resulting product morphology and properties. In the current study, CuxO/ZrOy composite materials were prepared using this technology and calcined to obtain electrode materials for the detection of cysteine (Cys). Essential comprehensive characterization techniques were employed to elucidate the heterojunction. The resulting electrode demonstrated a linear response to Cys within a concentration range of 0.5 nM to 1 µM, featuring a high sensitivity of 1035 µA·cm-2·µM-1 and a low detection limit of 97.3 nM. Thus, establishing a novel avenue for nonenzyme-based electrochemical sensors tailored for biologically active Cys detection through the implementation of a heterogeneous structure.

Protein-guided biomimetic nanomaterials: a versatile theranostic nanoplatform for biomedical applications.

Over the years, bioinspired mineralization-based approaches have been applied to synthesize multifunctional organic-inorganic nanocomposites. These nanocomposites can address the growing demands of modern biomedical applications. Proteins, serving as vital biological templates, play a pivotal role in the nucleation and growth processes of various organic-inorganic nanocomposites. Protein-mineralized nanomaterials (PMNMs) have attracted significant interest from researchers due to their facile and convenient preparation, strong physiological activity, stability, impressive biocompatibility, and biodegradability. Nevertheless, few comprehensive reviews have expounded on the progress of these nanomaterials in biomedicine. This article systematically reviews the principles and strategies for constructing nanomaterials using protein-directed biomineralization and biomimetic mineralization techniques. Subsequently, we focus on their recent applications in the biomedical field, encompassing areas such as bioimaging, as well as anti-tumor, anti-bacterial, and anti-inflammatory therapies. Furthermore, we discuss the challenges encountered in practical applications of these materials and explore their potential in future applications. This review aspired to catalyze the continued development of these bioinspired nanomaterials in drug development and clinical diagnosis, ultimately contributing to the fields of precision medicine and translational medicine.

Fluoride-Free Synthesis of 2D Titanium Carbide (MXenes) Assisted by scCO2 -Based Ternary Solution.

2D MXene-Ti3 C2 Tx holds great promise in various electronic applications, especially for electromagnetic interference (EMI) shielding devices and supercapacitors. Ti3 C2 Tx synthesis typically involves the use of hazardous fluorine-containing chemicals that can result in the formation of inert fluoride functional groups on the surface of Ti3 C2 Tx , severely degrading its properties and posing a threat to the performance of electron transfer among electrical devices. Herein, a supercritical carbon dioxide-based ternary solution (scCO2 /DMSO/HCl) to produce fluoride-free Ti3 C2 Tx in mild conditions (via 0.5 m HCl, 20 MPa, 32 °C) is reported. The fluorine-free Ti3 C2 Tx films electrode presents an excellent gravimetric capacitance of 320 F g-1 at 2 mV s-1 in 1 m H2 SO4 . Besides, it is demonstrated that fluorine-free Ti3 C2 Tx films exhibit outstanding EMI shielding efficiency of 53.12 dB at 2.5 µm thickness. The findings offer a mild and practical approach to producing fluoride-free Ti3 C2 Tx and open opportunities for exploring MXenes' potential applications in various fields.

Transition Metal Oxide-Decorated MXenes as Drugless Nanoarchitectonics for Enriched Nanocatalytic Chemodynamic Treatment.

Despite their unique characteristics, 2D MXenes with sole photothermal conversion ability are required to explore their superfluous abilities in biomedicine. The small-molecule-based chemotherapeutics suffer from various shortcomings of time-consuming and expensiveness concerning theoretical and performance (preclinical/clinical) checks. This study demonstrates the fabrication of Ti3C2 MXene nanosheets (TC-MX NSs) and subsequent decoration with transition metal oxides, that is, copper oxide (Cu2O/MX, CO-MX NCs) as drugless nanoarchitectonics for synergistic photothermal (PTT)-chemodynamic therapeutic (CDT) efficacies. Initially, the monolayer/few-layered TC-MX NSs are prepared using the chemical etching-assisted ultrasonic exfoliation method and then deposited with Cu2O nanoconstructs using the in situ reduction method. Further, the photothermal ablation under near-infrared (NIR)-II laser irradiation shows PTT effects of CO-MX NCs. The deposited Cu2O on TC-MX NSs facilitates the release of copper (Cu+) ions in the acidic microenvironment intracellularly for Fenton-like reaction-assisted CDT effects and enriched PTT effects synergistically. Mechanistically, these deadly free radicals intracellularly imbalance the glutathione (GSH) levels and result in mitochondrial dysfunction, inducing apoptosis of 4T1 cells. Finally, the in vivo investigations in BALB/c mice confirm the substantial ablation of breast carcinoma. Together, these findings demonstrate the potential synergistic PTT-CDT effects of the designed CO-MX NCs as drugless nanoarchitectonics against breast carcinoma.

NIR-II light triggered burst-release cascade nanoreactor for precise cancer chemotherapy.

The current strategy of co-delivering copper ions and disulfiram (DSF) to generate cytotoxic CuET faces limitations in achieving rapid and substantial CuET production, specifically in tumor lesions. To overcome this challenge, we introduce a novel burst-release cascade reactor composed of phase change materials (PCMs) encapsulating ultrasmall Cu2-xSe nanoparticles (NPs) and DSF (DSF/Cu2-xSe@PCM). Once triggered by second near-infrared (NIR-II) light irradiation, the reactor swiftly releases Cu2-xSe NPs and DSF, enabling catalytic reactions that lead to the rapid and massive production of Cu2-xSe-ET complexes, thereby achieving in situ chemotherapy. The mechanism of the burst reaction is due to the unique properties of ultrasmall Cu2-xSe NPs, including their small size, multiple defects, and high surface activity. These characteristics allow DSF to be directly reduced and chelated on the surface defect sites of Cu2-xSe, forming Cu2-xSe-ET complexes without the need for copper ion release. Additionally, Cu2-xSe-ET has demonstrated a similar (to CuET) anti-tumor activity through increased autophagy, but with even greater potency due to its unique two-dimensional-like structure. The light-triggered cascade of interlocking reactions, coupled with in situ explosive generation of tumor-suppressive substances mediated by the size and valence of Cu2-xSe, presents a promising approach for the development of innovative nanoplatforms in the field of precise tumor chemotherapy.

Sonodynamic therapy-based nanoplatforms for combating bacterial infections.

The rapid spread and uncontrollable evolution of antibiotic-resistant bacteria have already become urgent global to treat bacterial infections. Sonodynamic therapy (SDT), a noninvasive and effective therapeutic strategy, has broadened the way toward dealing with antibiotic-resistant bacteria and biofilms, which base on ultrasound (US) with sonosensitizer. Sonosensitizer, based on small organic molecules or inorganic nanoparticles, is essential to the SDT process. Thus, it is meaningful to design a sonosensitizer-loaded nanoplatform and synthesize the nanoplatform with an efficient SDT effect. In this review, we initially summarize the probable SDT-based antibacterial mechanisms and systematically discuss the current advancement in different SDT-based nanoplatform (including nanoplatform for organic small-molecule sonosensitizer delivery and nanoplatform as sonosensitizer) for bacterial infection therapy. In addition, the biomedical applications of SDT-involved multifunctional nanoplatforms are also discussed. We believe the innovative SDT-based nanoplatforms would become a highly efficient next-generation noninvasive therapeutic tool for combating bacterial infection.

Observing the Evolution of Metal Oxides in Liquids.

Metal oxides with diverse compositions and structures have garnered considerable interest from researchers in various reactions, which benefits from transmission electron microscopy (TEM) in determining their morphologies, phase, structural and chemical information. Recent breakthroughs have made liquid-phase TEM a promising imaging platform for tracking the dynamic structure, morphology, and composition evolution of metal oxides in solution under work conditions. Herein, this review introduces the recent advances in liquid cells, especially closed liquid cell chips. Subsequently, the recent progress including particle growth, phase transformation, self-assembly, core-shell nanostructure growth, and chemical etching are introduced. With the late technical advances in TEM and liquid cells, liquid-phase TEM is used to characterize many fundamental processes of metal oxides for CO2 reduction and water-splitting reactions. Finally, the outlook and challenges in this research field are discussed. It is believed this compilation inspires and stimulates more efforts in developing and utilizing in situ liquid-phase TEM for metal oxides at the atomic scale for different applications.

Hybrid nanoarchitectonics of molybdenum dioxide (MoO2) and doxorubicin (DOX) for synergistic chemo-photothermal-based breast carcinoma therapy.

Cancer has emerged as one of the severe ailments due to the uncontrolled proliferation rate of cells, accounting for millions of deaths annually. Despite the availability of various treatment strategies, including surgical interventions, radiation, and chemotherapy, tremendous advancements in the past two decades of research have evidenced the generation of different nanotherapeutic designs toward providing synergistic therapy. In this study, we demonstrate the assembly of a versatile nanoplatform based on the hyaluronic acid (HA)-coated molybdenum dioxide (MoO2) assemblies to act against breast carcinoma. The hydrothermal approach-assisted MoO2 constructs are immobilized with doxorubicin (DOX) molecules on the surface. Further, these MoO2-DOX hybrids are encapsulated with the HA polymeric framework. Furthermore, the versatile nanocomposites of HA-coated MoO2-DOX hybrids are systematically characterized using various characterization techniques, and explored biocompatibility in the mouse fibroblasts (L929 cell line), as well as synergistic photothermal (808-nm laser irradiation for 10 min, 1 W/cm2) and chemotherapeutic properties against breast carcinoma (4T1 cells). Finally, the mechanistic views concerning the apoptosis rate are explored using the JC-1 assay to measure the intracellular mitochondrial membrane potential (MMP) levels. In conclusion, these findings indicated excellent photothermal and chemotherapeutic efficacies, exploring the enormous potential of MoO2 composites against breast cancer.

Immune-regulating camouflaged nanoplatforms: A promising strategy to improve cancer nano-immunotherapy.

Although nano-immunotherapy has advanced dramatically in recent times, there remain two significant hurdles related to immune systems in cancer treatment, such as (namely) inevitable immune elimination of nanoplatforms and severely immunosuppressive microenvironment with low immunogenicity, hampering the performance of nanomedicines. To address these issues, several immune-regulating camouflaged nanocomposites have emerged as prevailing strategies due to their unique characteristics and specific functionalities. In this review, we emphasize the composition, performances, and mechanisms of various immune-regulating camouflaged nanoplatforms, including polymer-coated, cell membrane-camouflaged, and exosome-based nanoplatforms to evade the immune clearance of nanoplatforms or upregulate the immune function against the tumor. Further, we discuss the applications of these immune-regulating camouflaged nanoplatforms in directly boosting cancer immunotherapy and some immunogenic cell death-inducing immunotherapeutic modalities, such as chemotherapy, photothermal therapy, and reactive oxygen species-mediated immunotherapies, highlighting the current progress and recent advancements. Finally, we conclude the article with interesting perspectives, suggesting future tendencies of these innovative camouflaged constructs towards their translation pipeline.

Synthesis of porphyrin-based 2D ytterbium metal organic frameworks for efficient photodynamic therapy.

Photodynamic therapy (PDT), which relies on the photo-induced reactive oxygen species (ROS) to trigger tumor cells apoptosis, has attracted intense focus over the decades due to the minimum invasion, high-precision and controllable therapeutic processes. Tetra(4-carboxyphenyl) porphin (TCPP), as an effective PDT photosensitizer, can harness photons and generate singlet oxygen species (1O2) upon illumination; however, poor solubility and low loading rate greatly limit its further use. Although TCPP-based metal-organic-frameworks (MOFs) has been proposed to address these concerns, the relatively large size still limits their biomedical applications. Therefore, in this study, TCPP molecules are coordinated with Yb3+, growing into 2D Yb-TCPP MOFs by a wet chemical method; the as-prepared Yb-TCPP MOFs are around 200 nm in size and possess high 1O2 generation efficiency with low cytotoxicity. Due to TCPP is appeared as the organic frameworks of Yb-TCPP MOFs, the low loading rate problem is largely addressed; in addition, the absorbance of Yb-TCPP MOFs has been greatly expanded compared with free TCPP molecules due to the coordination with Yb3+, allowing the illumination at longer wavelength range, e.g. 655 nm, that possesses high penetration depth and low phototoxicity. Overall, we have prepared 2D Yb-TCPP MOFs suitable for the in vitro anticancer effect, revealing the potential of Yb-TCPP MOFs as the future anticancer agent.

Development of highly stable ICG-polymeric nanoparticles with ultra-high entrapment efficiency using supercritical antisolvent (SAS)-combined solution casting process.

Indocyanine green (ICG), a water-soluble near-infrared (NIR) photosensitizer, has been enormously regarded in tumor diagnosis and phototherapy. Although tremendous progress in establishing the nanocarrier-based delivery systems has been explored, several limitations of low ICG encapsulation and sophisticated fabrication process remain significant challenges in producing nanoplatforms, limiting the theranostic outcomes of ICG. According to the unique advantages of the supercritical antisolvent (SAS) process and solution casting method, a novel combination approach to obtain the ICG-loaded nanoparticles (ICG-PLO NPs) is demonstrated, in which SAS assisted-ICG nanoparticles (ICG NPs) are coated with polypeptide poly-l-ornithine (PLO) using solution casting approach. This unique nanoplatform with ultra-high drug encapsulation efficiency remarkably improved the aqueous and photothermal stability of ICG. Notably, the coating of PLO could improve the internalization level in cells and anticancer effect in vivo, comprehensively augmenting the cancer phototherapy effect of ICG. Together, the findings of novel particle formation by integrated strategy would certainly broaden the applications of supercritical fluid (SCF) technology, potentiating the design of nano-formulations of ICG for clinical translation.

Preparation of aripiprazole-poly(methyl vinyl ether-co-maleic anhydride) nanocomposites via supercritical antisolvent process for improved antidepression therapy.

Aripiprazole (ARI), a second-generation atypical antipsychotic drug approved for schizophrenia treatment, shows good efficacy against depression. However, the poorly aqueous solubility of ARI leads to low bioavailability and increased dose-related side effects, seriously limiting its application in pharmaceutics. Herein, we demonstrated the fabrication of ARI and poly (methyl vinyl ether-co-maleic anhydride) (PVMMA) composite nanoparticles (PA NPs) using the supercritical antisolvent (SAS) process for enhancing its water-solubility and curative anti-depressant effects. Initially, the optimal experimental conditions (ARI/PVMMA mass ratio of 1:6, pressure of 10 MPa, and solution flow rate of 0.75 ml min-1) were determined by a 23 factorial experimental design, resulting in the PA NPs with an excellent particle morphology. In vitro cell experiments showed that PA NPs significantly inhibited the inflammatory response caused by the microglia activation induced by lipopolysaccharide (LPS). Similarly, mice behavioral tests demonstrated that PA NPs significantly improved LPS-induced depression-like behavior. Importantly, compared with free ARI, the LPS-induced activation of microglia in the mouse brain and the expression of inflammatory factors in serum were significantly reduced after treatment with PA NPs. Together, the innovative PA NPs designed by SAS process might provide a candidate for developing new ARI-based nano-formulations.

Upconversion Luminescence via Anion Exchange in Perovskite Quantum Dots for Anticounterfeiting Inkjet Printing.

Lanthanide-doped upconversion nanoparticles (UCNPs) and cesium lead halide perovskite quantum dots (PeQDs) are highly compatible with each other: UCNPs produce anti-Stokes upconversion luminescence (UCL) under near-infrared (NIR) excitation and the emissive profiles of PeQDs can be conveniently tuned by varying the halide composition ratio. Therefore, in this study, UCNPs and PeQDs are mixed together, producing colorful UCL under 980 nm laser excitation. In addition, ZnI2 is used to vary the halide composition ratio of PeQDs and manipulate UCL in situ, thus adding more flexibility in UCL regulation. Finally, based on the above-mentioned discussion, a double-encrypted anticounterfeiting pattern is generated via sequentially printing ZnI2 solution and UCNP suspension on an A4 paper. Using PeQDs as the decrypting reagent, under the NIR excitation and decryption channel, the hidden information can be fully decrypted. The combination of UCNPs and PeQDs greatly expands the upconversion possibility, offers more feasibility in UCL regulation, and further promotes the practical applications.

Synergistic chemo-/photothermal therapy based on supercritical technology-assisted chitosan-indocyanine green/luteolin nanocomposites for wound healing.

Despite the success, it is highly challenging to battle against pathogenic biofilms-based chronic bacterial infections by conventional antibiotic therapy. Herein, we report a near-infrared (NIR)/acid-induced nanoplatform based on chitosan (CS)-coated indocyanine green (ICG, photosensitizer)/luteolin (LUT, a natural quorum sensing inhibitor) nanocomposites (ICG/LUT-CS) as antibacterial and antibiofilm agents for skin wound healing. Initially, the ICG/LUT nanoplatforms are prepared by the supercritical antisolvent technology and coated with the CS layer. The obtained ICG/LUT-CS with ultra-high encapsulation efficiency exhibited more favorable photothermal conversion effects and improved NIR laser/acid dual-induced drug release behavior than individual modalities, achieving exceptional bacteria-killing and biofilm elimination effects. Moreover, the ICG/LUT-CS realized the synergetic effects of chemotherapy and photothermal therapy outcomes for wound healing. Together, our findings provided an appealing strategy for the rapid preparation and future translational application of ICG/LUT-CS as an ideal agent for fighting against biofilm infections.

3D Printing of Ultrathin MXene toward Tough and Thermally Resistant Nanocomposites.

Liquid crystal display (LCD)-based 3D printing, a facile and cost-effective manufacturing technique, is often applied when fabricating objects with porcelain structures using photosensitive resins (PSRs). Currently, 3D printed constructions are typically used as models for demonstration purposes rather than industrial applications because of their poor performance. In this study, we prepared nanocomposites by incorporating Ti3C2 MXene nanosheets to enhance the overall characteristics of a PSR, including mechanical properties and thermal resistance. Notably, the designed nanocomposites showed optimum performance at an MXene loading of 0.5% w/w. The mechanical properties of the designed nanocomposites confirmed the enhanced ultimate tensile and flexural strengths (by 32.1% and 42.7%, respectively), at 0.5% w/w MXene loading. Moreover, the incorporated MXene presented no substantial influence on the toughness of the PSR. The glass transition and thermal degradation temperatures at 5% weight loss increased by 7.4 and 10.6 °C, respectively, resulting predominantly from the hydrogen bonding between the PSR and MXene. Together, the experimental results indicate that the designed PSR/MXene nanocomposites are expected to replace pristine resins for LCD printing in various practical applications.

Three-Dimensional Bioprinting of Decellularized Extracellular Matrix-Based Bioinks for Tissue Engineering.

Three-dimensional (3D) bioprinting is one of the most promising additive manufacturing technologies for fabricating various biomimetic architectures of tissues and organs. In this context, the bioink, a critical element for biofabrication, is a mixture of biomaterials and living cells used in 3D printing to create cell-laden structures. Recently, decellularized extracellular matrix (dECM)-based bioinks derived from natural tissues have garnered enormous attention from researchers due to their unique and complex biochemical properties. This review initially presents the details of the natural ECM and its role in cell growth and metabolism. Further, we briefly emphasize the commonly used decellularization treatment procedures and subsequent evaluations for the quality control of the dECM. In addition, we summarize some of the common bioink preparation strategies, the 3D bioprinting approaches, and the applicability of 3D-printed dECM bioinks to tissue engineering. Finally, we present some of the challenges in this field and the prospects for future development.

Antibody-based drug delivery systems for cancer therapy: Mechanisms, challenges, and prospects.

In recent years, antibody-based cancer therapy has emerged as one of the efficient therapeutic strategies, such as immune checkpoint inhibitors (ICIs), angiogenesis inhibitors, antibody-drug conjugates (ADCs), multi-specific antibodies, and chimeric antigen receptor T (CAR-T) cells, among others. To date, various drug delivery platforms have been developed to improve the bioavailability, delivery convenience, and reduced toxicity towards increased therapeutic efficacy of antibodies. Herein, we emphasize the clinical manifestations of various antibody-based tumor therapies, highlighting their mechanisms and applications for cancer therapy. Further, based on the problems to be solved in the current clinical application of antibodies, and combined with the advanced drug delivery technologies, we discuss the roles of antibody-based drug delivery systems (DDSs) in cancer therapy, such as enhanced patient compliance and regulating the tumor microenvironment for combined therapy. By expounding the importance of DDSs and discussing the challenges and prospects of their implementation, we suggest that pharmaceutical enterprises and scientists develop appropriate antibody-based delivery platforms.

Fabricating Highly Open Porous Microspheres (HOPMs) via Microfluidic Technology.

Compared to bulk scaffolds and direct injection of cells alone, the injectable modular units have garnered enormous interest in repairing malfunctioned tissues due to convenience in the packaging of cells, improved cell retention, and minimal invasiveness. Moreover, the porous conformation of these microscale carriers could enhance the medium exchange and improve the level of nutrients and oxygen supplies. The present study illustrates the convenient fabrication of poly(lactic-co-glycolic acid)-based highly open porous microspheres (PLGA-HOPMs) by the facile microfluidic technology for cell delivery applications. The resultant monodispersed PLGA-HOPMs possessed particle sizes of ~400 µm and open pores of ~50 µm with interconnecting windows. Briefly, the emulsified oil droplets (PLGA solution in dichloromethane, DCM), wrapped with the 7.5% (w/v) gelatin aqueous phase, were introduced into the 1% (w/v) continuous flowing poly(vinyl alcohol) (PVA) aqueous solution through the coaxial nozzle in the customized microfluidic setup. Subsequently, the microspheres were subjected to solvent extraction and lyophilization procedures, resulting in the production of HOPMs. Notably, various formulations (concentrations of PLGA and porogen) and processing parameters (emulsifying power, needle gauge, and flow rate of dispersed phase) play crucial roles in the qualities and characteristics of the resulting PLGA HOPMs. Moreover, these architectures might potentially encapsulate various other biochemical cues, such as growth factors, for extended drug discovery and tissue regeneration applications.

Nanoarchitectured prototypes of mesoporous silica nanoparticles for innovative biomedical applications.

Despite exceptional morphological and physicochemical attributes, mesoporous silica nanoparticles (MSNs) are often employed as carriers or vectors. Moreover, these conventional MSNs often suffer from various limitations in biomedicine, such as reduced drug encapsulation efficacy, deprived compatibility, and poor degradability, resulting in poor therapeutic outcomes. To address these limitations, several modifications have been corroborated to fabricating hierarchically-engineered MSNs in terms of tuning the pore sizes, modifying the surfaces, and engineering of siliceous networks. Interestingly, the further advancements of engineered MSNs lead to the generation of highly complex and nature-mimicking structures, such as Janus-type, multi-podal, and flower-like architectures, as well as streamlined tadpole-like nanomotors. In this review, we present explicit discussions relevant to these advanced hierarchical architectures in different fields of biomedicine, including drug delivery, bioimaging, tissue engineering, and miscellaneous applications, such as photoluminescence, artificial enzymes, peptide enrichment, DNA detection, and biosensing, among others. Initially, we give a brief overview of diverse, innovative stimuli-responsive (pH, light, ultrasound, and thermos)- and targeted drug delivery strategies, along with discussions on recent advancements in cancer immune therapy and applicability of advanced MSNs in other ailments related to cardiac, vascular, and nervous systems, as well as diabetes. Then, we provide initiatives taken so far in clinical translation of various silica-based materials and their scope towards clinical translation. Finally, we summarize the review with interesting perspectives on lessons learned in exploring the biomedical applications of advanced MSNs and further requirements to be explored.

Advances in Engineered Three-Dimensional (3D) Body Articulation Unit Models.

Indeed, the body articulation units, commonly referred to as body joints, play significant roles in the musculoskeletal system, enabling body flexibility. Nevertheless, these articulation units suffer from several pathological conditions, such as osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, gout, and psoriatic arthritis. There exist several treatment modalities based on the utilization of anti-inflammatory and analgesic drugs, which can reduce or control the pathophysiological symptoms. Despite the success, these treatment modalities suffer from major shortcomings of enormous cost and poor recovery, limiting their applicability and requiring promising strategies. To address these limitations, several engineering strategies have been emerged as promising solutions in fabricating the body articulation as unit models towards local articulation repair for tissue regeneration and high-throughput screening for drug development. In this article, we present challenges related to the selection of biomaterials (natural and synthetic sources), construction of 3D articulation models (scaffold-free, scaffold-based, and organ-on-a-chip), architectural designs (microfluidics, bioprinting, electrospinning, and biomineralization), and the type of culture conditions (growth factors and active peptides). Then, we emphasize the applicability of these articulation units for emerging biomedical applications of drug screening and tissue repair/regeneration. In conclusion, we put forward the challenges and difficulties for the further clinical application of the in vitro 3D articulation unit models in terms of the long-term high activity of the models.