Intra-articular injection of miRNA-1 agomir, a novel chemically modified miRNA agonists alleviates osteoarthritis (OA) progression by downregulating Indian hedgehog in rats.

Our objective in this study is to determine whether intra-articular injection of miRNA-1 can attenuate the progression of OA in rats by down regulating Ihh. Knee chondrocytes were isolated from male Sprague-Dawley rats aged 2-3 days. Second-generation chondrocytes were transfected with miR-1 mimic and empty vector with lipo3000 for 6 h and then stimulated with 10 ng/mL IL-1ß for 24 h. OA-related and cartilage matrix genes were quantified using real-time quantitative polymerase chain reaction (RT-qPCR). Two-month-old male Sprague-Dawley rats were divided into three groups (n = 30?): sham operation group + 50 µL saline, anterior cruciate ligament transection (ACLT) group + 50 µL miR-1 agomir (concentration), and control group ACLT + 50 µL miR-1 agomir. Treatment was started one week after the operation. All animals were euthanized eight weeks after the operation. X-rays and micro-CT were used to detect imaging changes in the knee joints. FMT was used to monitor joint inflammation in vivo. Safranin O staining was used to detect morphological changes in articular cartilage. Immunohistochemistry was used to detect Col2, Col10, metalloproteinase-13 (MMP-13). RT-qPCR was used to detect gene changes includingmiR-1, Col2, Col10, MMP-13, Ihh, Smo, Gli1, Gli2, and Gli3. Overexpression of miR-1 in IL-1ß-stimulated chondrocytes reduced the levels of Ihh, MMP-13, and Col10 but increased the levels of Col2 and aggrecan. Intra-articular injection of miR-1 agomir reduced osteophyte formation, inflammation, and prevented cartilage damage. RT-qPCR results indicated that the miR-1 agomir increased articular cartilage anabolism and inhibited cartilage catabonism. miR-1 can attenuate the progression of OA by downregulating Ihh.

Quantum-Confined-Superfluidics-Enabled Multiresponsive MXene-Based Actuators.

MXene, renowned for its natural "quantum-confined-superfluidic" (QSF) channels, demonstrates superior electrical/thermal conductivity, favorable hydrophilicity, and remarkable mechanical strength, rendering it an ideal candidate for multiresponsive actuators, which are promising for soft electronics and robots. Currently, most MXene-based actuators are mainly prepared by combining an active layer and an inner layer, with only a few utilizing regulated QSF channels. However, tailoring QSF channels for multiresponsive actuators is extremely challenging. Herein, we introduce a multiresponsive graphene oxide (GO)&Fe3O4/MXene actuator that can respond to humidity, light, heat, electricity, and magnetic fields by constructing asymmetric QSF channels. The asymmetric water adsorption, transportation, and desorption behaviors, controlled by the different QSF channels between the GO&Fe3O4 layer and the MXene layer, enable the multiresponsiveness of the actuator. As proof-of-concept demonstrations, several smart devices, such as a bionic crab-like crawler, a transporting flower robot, and a smart gripper, are prepared, holding great potential for advancing future soft robotics.

3D Bioprinting-Based Dopamine-Coupled Flexible Material for Nasal Cartilage Repair.

INTRODUCTION: Since 3D printing can be used to design implants according to the specific conditions of patients, it has become an emerging technology in tissue engineering and regenerative medicine. How to improve the mechanical, elastic and adhesion properties of 3D-printed photocrosslinked hydrogels is the focus of cartilage tissue repair and reconstruction research. MATERIALS AND METHODS: We established a strategy for toughening hydrogels by mixing GelMA-DOPA (GD), which is prepared by coupling dopamine (DA) with GelMA, with HAMA, bacterial cellulose (BC) to produce composite hydrogels (HB-GD). HB-GD hydrogel scaffolds were characterized in vitro by scanning electron microscopy (SEM), Young's modulus, swelling property and rheological property tests. And biocompatibility and chondrogenic ability were tested by live/dead staining, DNA quantitative analysis and immunofluorescence staining. Combined with 3D bioprinting technology, mouse chondrocytes (ADTC5) were added to form a biological chain to construct an in vitro model, and the feasibility of the model for nasal cartilage regeneration was verified by cytology evaluation. RESULTS: With the increase of GD concentration, the toughness of the composite hydrogel increased (47.0 ± 2.7 kPa (HB-5GD)-158 ± 3.2 kPa (HB-20GD)), and it had excellent swelling properties, rheological properties and printing properties. The HB-GD composite hydrogel promoted the proliferation and differentiation of ATDC5. Cells in 3D printed scaffolds had higher survival rates (> 95%) and better protein expression than the encapsulated cultures. CONCLUSION: The HB-10GD hydrogel can be made into a porous scaffold with precise shape, good internal pore structure, high mechanical strength and good swelling rate through extrusion 3D printing. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

A heparin-functionalized bioink with sustained delivery of vascular endothelial growth factor for 3D bioprinting of prevascularized dermal constructs.

Skin tissue engineering faces challenges due to the absence of vascular architecture, impeding the development of permanent skin replacements. To address this, a heparin-functionalized 3D-printed bioink (GH/HepMA) was formulated to enable sustained delivery of vascular endothelial growth factor (VEGF), comprising 0.3 % (w/v) hyaluronic acid (HA), 10 % (w/v) gelatin methacrylate (GelMA), and 0.5 % (w/v) heparin methacrylate (HepMA). The bioink was then used to print dermal constructs with angiogenic functions, including fibroblast networks and human umbilical vein endothelial cell (HUVEC) networks. GH/HepMA, with its covalently cross-linked structure, exhibits enhanced mechanical properties and heparin stability, allowing for a 21-day sustained delivery of VEGF. Cytocompatibility experiments showed that the GH/HepMA bioink supported fibroblast proliferation and promoted collagen I production. With VEGF present, the GH/HepMA bioink promoted HUVEC proliferation, migration, as well as the formation of a richer capillary-like network. Furthermore, HA within the GH/HepMA bioink enhanced rheological properties and printability. Additionally, 3D-bioprinted dermal constructs showed significant deposition of collagen I and III and mature stable capillary-like structures along the axial direction. In summary, this study offers a promising approach for constructing biomimetic multicellular skin substitutes with angiogenesis-induced functions.

Effective Combination of Targeted Therapies with Sonodynamic Treatment for Use in Exploring Differences in Therapeutic Efficacy across Organelle Targets.

Acoustic kinetic therapy systems that target specific organelles can improve the precision of a sonosensitizer, which is a perfect combination of targeted therapy and sonodynamic therapy (SDT) and plays an important role in current acoustic kinetic therapy. In this study, we loaded PpIX, a sonosensitizer, on targeted-functional carbon dots (CDs) via an amide reaction and then generated the mitochondria-targeted system (Mit-CDs-PpIX) and nucleus-targeted system (Nuc-CDs-PpIX), respectively, to deliver the sonosensitizer. Both systems exhibited minimal cytotoxicity in the absence of ultrasound stimulation. The efficacy of the targeted SDT systems was investigated using methylthiazol tetrazolium (MTT) assays, live/dead staining, flow cytometry, etc. Compared with the free PpIX and mitochondria-targeted system, the nucleus-targeted system is more potent in killing effect under ultrasound stimulation and induces apoptosis with higher intensity. To achieve the equal killing effect, the effective concentration of Nuc-CDs-PpIX is just one third of that of Mit-CDs-PpIX.

Magneto-Mechanical Coupling Study of Magnetorheological Elastomer Thin Films for Sensitivity Enhancement.

Magnetorheological elastomer thin films (MREFs) exhibit remarkable deformability and an adjustable modulus under magnetic fields, rendering them promising in fields such as robotics, flexible sensors, and biomedical engineering. Here, we fabricated MREF by introducing magnetostrictive particles (MSPs) and evaluated the magneto-mechanical coupling effect on the enhancement of sensitivity. The saturation magnetization (Ms) in a parallel anisotropic TbDyFe-PDMS MREF was 5.8 emu/g, and the initial tensile modulus was 55% greater than that of an Iso MREF. We propose a nonlinear magnetorheological formula on the magnetostriction effect, incorporating magnetic dipole interactions and the nonlinear prestress of magnetic particles. This formula highlights the complex nonlinear relationship between the external magnetic field (H) and the key parameters that affect the enhanced MR effect of MSPs-MREF, such as saturation magnetization, remanence (Mr), magnetostriction constant (λs) and stress deviator in ferromagnetic particles (Sed) in the magnetic chain structure. Furthermore, we validate the influence of the key parameters of the rectified magnetorheological formula on a nonlinear magneto-mechanical behavior of MSPs-MREF in PDMS-based MSPs-MREF models by using finite-element simulations. Finally, we developed a biosensor based on MSPs-MREF to detect human serum albumin at low concentrations in human urine samples. There is a 4-fold increase in sensitivity, a lower detection of limit (0.442 µg/mL), and a faster response time (15 min) than traditional biosensors, which in the future might provide an effective way of detecting biomolecules of low concentrations.

A BTO/PVDF/PDMS Piezoelectric Tangential and Normal Force Sensor Inspired by a Wind Chime.

There is a growing demand for flexible pressure sensors in environmental monitoring and human-robot interaction robotics. A flexible and susceptible sensor can discriminate multidirectional pressure, thus effectively detecting signals of small environmental changes and providing solutions for personalized medicine. This paper proposes a multidimensional force detection sensor inspired by a wind chime structure with a three-dimensional force structure to detect and analyze normal and shear forces in real time. The force-sensing structure of the sensor consists of an upper and lower membrane on a polydimethylsiloxane substrate and four surrounding cylinders. A piezoelectric hemisphere is made of BTO/PVDF/PDMS composite material. The sensor columns in the wind chime structure surround the piezoelectric layer in the middle. When pressure is applied externally, the sensor columns are connected to the piezoelectric layer with a light touch. The piezoelectric hemisphere generates a voltage signal. Due to the particular structure of the sensor, it can accurately capture multidimensional forces and identify the direction of the external force by analyzing the position of the sensor and the output voltage amplitude. The development of such sensors shows excellent potential for self-powered wearable sensors, human-computer interaction, electronic skin, and soft robotics applications.

A mechanical biosensor based on membrane-mediated magneto-stress-electric coupled sensitization for human serum albumin detection.

Recently, mechanical biosensors have attracted more attention on single molecule detection due to its high accuracy, low cost, and convenience. However, the sensitivity of the mechanical biosensors restricted their clinical application. Herein, a mechanical biosensor based on membrane-mediated magneto-stress-electric coupled sensitization (MSEC-MMB) was developed to enhance performance. Through introducing Fe3O4 nanoparticles (MNPs) to traditional stress-electric biosensors and applying a magnetic field, a magneto-stress-electric coupled biosensing system was constructed. The sensitivity of the MSEC-MMB was improved via enhancing the deformation of the mechanical membrane, which was demonstrated by detecting HSA. The optimal limit of detection (LOD) was 24 pg mL-1 under a magnetic field of 50 mT. The LOD was significantly 1 order of magnitude lower than that without the magnetic field. Besides, the MSEC-MMB showed a high specificity, selectivity, and stability. The clinical proteinuria samples were accurately detected, suggesting a good practicability of the MSEC-MMB. All these results proved the high sensitivity and practicality of the MSEC-MMB and provide a platform for early nephropathy diagnosis.

Constructing epidermal rete ridges using a composite hydrogel to enhance multiple signaling pathways for the maintenance of epidermal stem cell niche.

The undulating microstructure rete ridge (RR) located at the junction between the dermis and epidermis plays a crucial role in improving skin mechanical properties and maintaining skin homeostasis. However, the investigation of RR microstructures is usually neglected in current tissue engineering for skin regeneration. Here, to create an epidermal model with RR microstructures, keratinocytes were cultured on a patterned GelMA-PEGDA hydrogel constructed using molding technology. Furthermore, grafting acryloylated Arg-Gly-Asp (RGD) peptides on the hydrogel surface significantly improved cell adhesion, fusion, and development. RT-PCR, Western blot, and immunofluorescence staining confirmed that cells on RR microstructures exhibited higher gene and protein expression associated with epidermal stem cells. RNA sequencing analysis of cells on RR microstructure showed higher gene expression profiles related to stem cell maintenance, basement membrane formation, and epidermal development. Furthermore, RT-PCR analysis of epidermal models of various dimensions demonstrated that smaller microstructures were more conducive to epidermal stem cell marker gene expression, which is analogous to human skin. Overall, we have successfully developed a method for integrating RR microstructures into an epidermal model that mimics natural skin to maintain epidermal stem cell niche, providing a valuable reference for researching skin regeneration within the fields of tissue engineering and regenerative medicine. STATEMENT OF SIGNIFICANCE: This study presents a method for precisely fabricating microstructures of skin rete ridges using composite hydrogels, thereby creating a skin model that mimics natural human skin. The findings reveal that this microstructure provides a stem cell niche that regulates the pathways and promotes the expression of proteins related to epidermal stem cells. This work advances the functional properties of tissue engineered skin and holds promise for improving the therapeutic efficacy of artificial skin grafts for the skin wounds.

A mechanical HSA biosensor based on multi-field-coupling-mediated magnetic sensitization strategy.

The conventional mechanical biosensor based on stress and electrical conversion can be an effective method to detect key human biomarkers for clinical diagnosis and early disease prevention. However, the applications of this type of biosensor are greatly limited due to their unsatisfactory sensitivity. In this work, a magnetic-sensitized (MS) mechanical biosensor based on multi-field coupling was developed for higher sensitivity, giving access to detect human serum albumin (HSA). Via introducing secondary magnetic antibodies labeled with magnetized Fe2O3 nanoparticles to the stress and electrical conversion element of the MS-biosensor, the multi-field coupling was realized based on stress, electricity, and magnetism. Under the action of the magnetic field, the magnetic force of the secondary magnetic antibody and the stress of antigen-antibody binding jointly drove and enhanced the deformation of the MS-biosensor, amplifying the electrical signal, and realizing magnetic sensitization. The HSA was detected by the MS-biosensor at a range of 0-80 µg/mL with a limit of detection (LOD) of 0.14 µg/mL, demonstrating the high performance of the MS-biosensor. Moreover, the MS-biosensor showed high selectivity, specificity, and stability, indicating that the magnetic sensitization strategy of the MS-biosensor was significant for the clinical application of mechanical biosensors.

3D printing to construct in vitro multicellular models of melanoma.

Currently, there is a lack of suitable models for in-vitro studies of malignant melanoma and traditional single cell culture models no longer reproduce tumor structure and physiological complexity well. The tumor microenvironment is closely related to carcinogenesis and it is particularly important to understand how tumor cells interact and communicate with surrounding nonmalignant cells. Three-dimensional (3D) in vitro multicellular culture models can better simulate the tumor microenvironment due to their excellent physicochemical properties. In this study, 3D composite hydrogel scaffolds were prepared from gelatin methacrylate and polyethylene glycol diacrylate hydrogels by 3D printing and light curing techniques, and 3D multicellular in vitro tumor culture models were established by inoculating human melanoma cells (A375) and human fibroblasts cells on them. The cell proliferation, migration, invasion, and drug resistance of the 3D multicellular in vitro model was evaluated. Compared with the single-cell model, the cells in the multicellular model had higher proliferation activity and migration ability, and were easy to form dense structures. Several tumor cell markers, such as matrix metalloproteinase-9 (MMP-9), MMP-2, and vascular endothelial growth factor, were highly expressed in the multicellular culture model, which were more favorable for tumor development. In addition, higher cell survival rate was observed after exposure to luteolin. The anticancer drug resistance result of the malignant melanoma cells in the 3D bioprinted construct demonstrated physiological properties, suggesting the promising potential of current 3D printed tumor model in the development of personalized therapy, especially for discovery of more conducive targeted drugs.

Path Planning for Obstacle Avoidance of Robot Arm Based on Improved Potential Field Method.

In medical and surgical scenarios, the trajectory planning of a collaborative robot arm is a difficult problem. The artificial potential field (APF) algorithm is a classic method for robot trajectory planning, which has the characteristics of good real-time performance and low computing consumption. There are many variants of the APF algorithm, among which the most widely used variants is the velocity potential field (VPF) algorithm. However, the traditional VPF algorithm has inherent defects and problems, such as easily falling into local minimum, being unable to reach the target, poor dynamic obstacle avoidance ability, and safety and efficiency problems. Therefore, this work presents the improved velocity potential field (IVPF) algorithm, which considers direction factors, obstacle velocity factor, and tangential velocity. When encountering dynamic obstacles, the IVPF algorithm can avoid obstacles better to ensure the safety of both the human and robot arm. The IVPF algorithm also does not easily fall into a local problem when encountering different obstacles. The experiments informed the RRT* algorithm, VPF algorithm, and IVPF algorithm for comparison. Compared with the informed RRT* and VPF algorithm, the result of experiments indicate that the performances of the IVPF algorithm have significant improvements when dealing with different obstacles. The main aim of this paper is to provide a safe and efficient path planning algorithm for the robot arm in the medical field. The proposed algorithm can ensure the safety of both the human and the robot arm when the medical and surgical robot arm is working, and enables the robot arm to cope with emergencies and perform tasks better. The application of the proposed algorithm could make the collaborative robots work in a flexible and safe condition, which could open up new opportunities for the future development of medical and surgical scenarios.

A cost-effective smartphone-based device for rapid C-reaction protein (CRP) detection using magnetoelastic immunosensor.

C-Reaction protein (CRP) is a marker of nonspecific immunity for vital signs and wound assessment, and it can be used to diagnose infections in clinical medicine. However, measuring CRP level currently requires hospital-based instruments, high-cost reagents, and a complex process, all of which have limited its full capabilities for self-detection, a growing trend in modern medicine. In this study, we developed a novel smartphone-based device using advanced methods of magnetoelastic immunosensing to mitigate these limitations. We combined a system-on-chip (SoC) hardware architecture with smartphone apps to realize the sampling of resonance frequency shift on magnetoelastic chips, which can determine the ultra-sensitivity to mass change caused by the binding of anti-CRP antibody and CRP. Through detecting a multi-group of samples, we found that the resonance frequency shift was linearly proportional to the CRP concentration in the range from 0.1 to 100 µg mL-1, with a sensitivity of 12.90 Hz µg-1 mL-1 and a detection limit of 2.349 × 10-4 µg mL-1. Meanwhile, compared with the large-scale instrument used in clinical settings, the performance of our device was stable and significantly more portable, rapid and cost-effective, offering excellent potential for modern home-based diagnosis.

End-to-End Automatic Classification of Retinal Vessel Based on Generative Adversarial Networks with Improved U-Net.

The retinal vessels in the human body are the only ones that can be observed directly by non-invasive imaging techniques. Retinal vessel morphology and structure are the important objects of concern for physicians in the early diagnosis and treatment of related diseases. The classification of retinal vessels has important guiding significance in the basic stage of diagnostic treatment. This paper proposes a novel method based on generative adversarial networks with improved U-Net, which can achieve synchronous automatic segmentation and classification of blood vessels by an end-to-end network. The proposed method avoids the dependency of the segmentation results in the multiple classification tasks. Moreover, the proposed method builds on an accurate classification of arteries and veins while also classifying arteriovenous crossings. The validity of the proposed method is evaluated on the RITE dataset: the accuracy of image comprehensive classification reaches 96.87%. The sensitivity and specificity of arteriovenous classification reach 91.78% and 97.25%. The results verify the effectiveness of the proposed method and show the competitive classification performance.

Highly Sensitive Magnetoelastic Biosensor for Alpha2-Macroglobulin Detection Based on MnFe2O4@chitosan/MWCNTs/PDMS Composite.

The need for Alpha2-Macroglobulin (α2-M) detection has increased because it plays an important role in the diagnosis of diabetic nephropathy (DN). However, few sensors can realize the high-sensitive detection for α2-M with characteristics of being fast, flexible, wearable and portable. Herein, a biosensor based on a MnFe2O4@chitosan/MWCNTs/PDMS composite film was developed for α2-M detection. Due to the excellent magnetoelastic effect of MnFe2O4 nanoparticles, the stress signal of the biosensor surface induced by the specific antibody-antigen binding was transformed into the electrical and magnetic signal. Chitosan-coated MnFe2O4 particles were used to provide biological modification sites for the α2-M antibody, which simplified the conventional biological functionalization modification process. The MnFe2O4@chitosan particles were successfully prepared by a chemical coprecipitation method and the property was studied by TEM, FT-IR and XRD. MWCNTs were employed to enhance electrical conductivity and the sensitivity of the biosensor. The detection limit (LOD) was reduced to 0.1299 ng·mL-1 in the linear range from 10 ng∙mL-1 to 100 µg·mL-1, which was significantly lower than the limit of health diagnostics. The biosensor is fabricated by a simple method, with advantages of being rapid and highly-sensitive, and having selective detection of α2-M, which provides a novel method for the early diagnosis of DN, and it has potential in the point of care (PoC) field.

3D Bioprinting Using Synovium-Derived MSC-Laden Photo-Cross-Linked ECM Bioink for Cartilage Regeneration.

In this study, inspired by the components of cartilage matrix, a photo-cross-linked extracellular matrix (ECM) bioink composed of modified proteins and polysaccharides was presented, including gelatin methacrylate, hyaluronic acid methacrylate, and chondroitin sulfate methacrylate. The systematic experiments were performed, including morphology, swelling, degradation, mechanical and rheological tests, printability analysis, biocompatibility and chondrogenic differentiation characterization, and RNA sequencing (RNA-seq). The results indicated that the photo-cross-linked ECM hydrogels possessed suitable degradation rate and excellent mechanical properties, and the three-dimensional (3D) bioprinted ECM scaffolds obtained favorable shape fidelity and improved the basic properties, biological properties, and chondrogenesis of synovium-derived MSCs (SMSCs). The strong stimulation of transforming growth factor-beta 1 (TGF-ß1) enhanced the aggregation, proliferation, and differentiation of SMSCs, thereby enhancing chondrogenic ECM deposition. In vivo animal experiments and gait analysis further confirmed that the ECM scaffold combined with TGF-ß1 could effectively promote cartilage regeneration and functional recovery of injured joints. To sum up, the photo-cross-linked ECM bioink for 3D printing of functional cartilage tissue may become an attractive strategy for cartilage regeneration.

3D bioprinting of heterogeneous tissue-engineered skin containing human dermal fibroblasts and keratinocytes.

Three-dimensional (3D) printed skin substitutes have great potential for wound healing. However, current 3D printed skin models are limited in simulating heterogeneity and complexity of skin tissue due to the lack of customized bioinks optimized for different skin layers. Herein, different gelatin methacrylate (GelMA)/nano-cellulose (BNC) bioink formulations were used to develop heterogeneous tissue-engineered skin (HTS) containing layers of fibroblast networks with larger pores, basal layers with smaller pores, and multilayered keratinocytes. The results revealed that the 10%GelMA/0.3%BNC bioink was better to model bioprinted dermis due to its high printability and cell-friendly sparse microenvironment. Additionally, the 10%GelMA/1.5%BNC bioink as the basal layer presented a dense network and sufficient material stiffness to support the establishment of keratinocyte confluent monolayers. The HTS not only had the ability to remodel the extracellular matrix but also supported epidermis reconstruction and stratification in vitro, with the epidermal thickness growing to 80 µm after 14 days. Furthermore, the full-thickness wound healing experiments demonstrated that the HTS promoted granulation tissue regeneration and improved wound healing quality. The generated skin of the HTS group had hair follicles and early-stage rete ridge structures, which were similar to normal skin in vivo. The HTS may deliver effective skin grafts for future clinical treatments.

3D printed-electrospun PCL/hydroxyapatite/MWCNTs scaffolds for the repair of subchondral bone.

Osteochondral defect caused by trauma or osteoarthritis exhibits a major challenge in clinical treatment with limited symptomatic effects at present. The regeneration and remodeling of subchondral bone play a positive effect on cartilage regeneration and further promotes the repair of osteochondral defects. Making use of the strengths of each preparation method, the combination of 3D printing and electrospinning is a promising method for designing and constructing multi-scale scaffolds that mimic the complexity and hierarchical structure of subchondral bone at the microscale and nanoscale, respectively. In this study, the 3D printed-electrospun poly(ɛ-caprolactone)/nano-hydroxyapatites/multi-walled carbon nanotubes (PCL/nHA/MWCNTs) scaffolds were successfully constructed by the combination of electrospinning and layer-by-layer 3D printing. The resulting dual-scale scaffold consisted of a dense layer of disordered nanospun fibers and a porous microscale 3D scaffold layer to support and promote the ingrowth of subchondral bone. Herein, the biomimetic PCL/nHA/MWCNTs scaffolds enhanced cell seeding efficiency and allowed for higher cell-cell interactions that supported the adhesion, proliferation, activity, morphology and subsequently improved the osteogenic differentiation of bone marrow mesenchymal stem cells in vitro. Together, this study elucidates that the construction of 3D printed-electrospun PCL/nHA/MWCNTs scaffolds provides an alternative strategy for the regeneration of subchondral bone and lays a foundation for subsequent in vivo studies.

Multilayer Heterogeneous Membrane Biosensor Based on Multiphysical Field Coupling for Human Serum Albumin Detection.

A factor closely associated with renal disease status in clinical diagnosis is abnormal human serum albumin (HSA) concentration levels in human body fluids urine, serum, etc. The surface stress biosensor was developed as a new type of biosensor to detect protein molecule concentration and has a wide range of clinical applications. However, further sensitivity improvement is required to achieve higher detection performance. Herein, MXene/PDMS/Fe3O4/PDMS of the multilayer heterogeneous membrane biosensor (MHBios) based on the coupling of the magnetic field, electric field, and surface stress field was successfully developed to achieve high sensitivity HSA detection through magnetic sensitization. The modified antibody specifically binds to HSA at the AuNP layer, allowing the biosensor to convert the surface stress caused by PDMS film deformation into an electrical signal. When the biosensor was exposed to a uniform magnetic field, the conductive path of the conductive layer was reshaped further as the magnetic force amplified the deformation of the PDMS film, enhancing the conversion of biological signals to electrical signals. The results exhibited that the detection limit (LOD) of the MHBios was 78 ng/mL when HSA concentration was 0-50 µg/mL, which was markedly lower than the minimum diagnostic limit of microalbuminuria. Furthermore, the MHBios detected HSA in actual samples, confirming the potential for early disease screening.

Collagen-coated agarose-chitosan scaffold used as a skin substitute.

A single biomaterial is disadvantageous for constructing skin in vitro, so a mixed biomaterial is more conducive to skin research. In this study, agarose-chitosan scaffolds with a final concentration of 4% were constructed by freeze-drying, in which the concentration ratios of agarose to chitosan were 1:3, 2:2, and 3:1. The scaffolds were coated with a 3 mg/ml collagen solution, and the mechanical properties were evaluated by studying density, porosity, swelling rate, and degradation rate. The results demonstrated that the agarose-chitosan scaffolds were porous, with porosity reaching 93%. Their densities ranged from 0.1 to 0.16 g/cm3 . Analysis of Young's modulus showed that the mechanical properties of the agarose-chitosan scaffolds were significantly enhanced when the agarose content in the agarose-chitosan scaffolds was increased. Moreover, the density and Young's modulus of the agarose-chitosan scaffolds of different concentration ratios were significantly different (p < 0.01). These scaffolds can withstand a certain amount of external pressure, such as that of human skin, making them more suitable for further skin replacement research. In addition, the results of thiazolyl blue tetrazolium bromide (MTT) cell assay and immunofluorescence staining showed that the collagen-coated agarose-chitosan scaffolds were conducive to keratinocyte proliferation and differentiation. The MTT results revealed significant differences between the agarose-chitosan scaffolds coated with collagen and the agarose-chitosan scaffolds without collagen (p < 0.05). This study provides the potential for in vitro skin research and applications.