Three-dimensional Scaffolds Research Articles

Three-dimensional gas-foamed scaffolds decorated with metal phenolic networks for cartilage regeneration

Inflammation is a major impediment to the healing of cartilage injuries, yet bioactive scaffolds suitable for cartilage repair in inflammatory environments are extremely rare. Herein, we utilized electrospinning to fabricate a two-dimensional nanofiber scaffold (2DS), which was then subjected to gas foaming to obtain a three-dimensional scaffold (3DS). 3DS was modified with metal phenolic networks (MPNs) composed of epigallocatechin gallate (EGCG) and strontium ions (Sr2+) to afford a MPNs-modified 3D scaffold (3DS-E). Gas-foamed scaffold exhibited multilayered structure conducive to cellular infiltration and proliferation. Compared to other groups, 3DS-E better preserved chondrocytes under interleukin (IL)-1β induced inflammatory environment, showing less apoptosis of chondrocytes and higher expression of cartilage matrix. Additionally, 3DS-E facilitated the regeneration of more mature cartilage in vivo, reduced cell apoptosis, and decreased the expression of pro-inflammatory cytokines.Taken together, 3DS-E may offer an ideal candidate for cartilage regeneration.

In-situ building of multiscale porous NiFeZn/NiZn-Ni heterojunction for superior overall water splitting

The development of efficient nonprecious bifunctional electrocatalysts for water electrolysis is crucial to enhance the sluggish kinetics of the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). A self-supporting, multiscale porous NiFeZn/NiZn-Ni catalyst with a triple interface heterojunction on nickel foam (NF) (NiFeZn/NiZn-Ni/NF) was in-situ fabricated using an electroplating−annealing−etching strategy. The unique multi- interface engineering and three-dimensional porous scaffold significantly modify the mass transport and electron interaction, resulting in superior bifunctional electrocatalytic performance for water splitting. The NiFeZn/NiZn-Ni/NF catalyst demonstrates low overpotentials of 187 mV for HER and 320 mV for OER at a current density of 600 mA/cm², along with high durability over 150 h in alkaline solution. Furthermore, an electrolytic cell assembled with NiFeZn/NiZn-Ni/NF as both the cathode and anode achieves the current densities of 600 and 1000 mA/cm2 at cell voltages of 1.796 and 1.901 V, respectively, maintaining the high stability at 50 mA/cm2 for over 100 h. These findings highlight the potential of NiFeZn/NiZn-Ni/NF as a cost-effective and highly efficient bifunctional electrocatalyst for overall water splitting.

A metalloenzyme platform for catalytic asymmetric radical dearomatization.

Catalytic asymmetric dearomatization represents a powerful means to convert flat aromatic compounds into stereochemically well-defined three-dimensional molecular scaffolds. Using new-to-nature metalloredox biocatalysis, we describe an enzymatic strategy for catalytic asymmetric dearomatization via a challenging radical mechanism that has eluded small-molecule catalysts. Enabled by directed evolution, new-to-nature radical dearomatases P450rad1-P450rad5 facilitated asymmetric dearomatization of a broad spectrum of aromatic substrates, including indoles, pyrroles and phenols, allowing both enantioconvergent and enantiodivergent radical dearomatization reactions to be accomplished with excellent enzymatic control. Computational studies revealed the importance of additional hydrogen bonding interactions between the engineered metalloenzyme and the reactive intermediate in enhancing enzymatic activity and enantiocontrol. Furthermore, designer non-ionic surfactants were found to significantly accelerate this biotransformation, providing an alternative means to promote otherwise sluggish new-to-nature biotransformations. Together, this evolvable metalloenzyme platform opens up new avenues to advance challenging catalytic asymmetric dearomatization processes involving free radical intermediates.

Enhanced water and urea electrolysis at industrial scale current density using self-supported VxNi1-xO trifunctional catalysts

An advance of highly efficient nanostructured electrocatalysts based on non-noble metals for water electrolysis and urea oxidation reaction (UOR) are of great significance for urea-enriched wastewater remediation and producing hydrogen. Herein, we report VxNi1-xO catalysts supported on three-dimensional Ni-foam scaffold for catalytic water and urea electrolysis. VxNi1-xO catalysts show rapid water and urea electrolysis due to enhanced electrochemical surface area (ECSA). Most important of all, the urea oxidation reaction has a lower potential of 1.418V vs RHE as compared to oxygen evolution reaction (1.684 V vs RHE) system to generate 100 mA/cm2. Additionally, a two-electrode cell for bi-functional water electrolysis generates 100 mA/cm2 at a potential of 2.10 V at 20 °C and just 1.86 V at 60 °C temperature due to regulated the adsorption/desorption of intermediates species, enhanced charge and mass transport, and easier desorption of oxygen molecules from the anode. The stability of VxNi1-xO catalyst was measured at 1000 mA/cm2 current density for up to 17 h.

Asymmetric Paired Electrolysis: Enantioselective Alkylation of Sulfonylimines via C(sp3)-H Functionalization.

Enantioselective transformation of ubiquitous C(sp3)-H bonds into three-dimensional chiral scaffolds is of longstanding interest to synthetic chemists. Herein, an asymmetric paired electrolysis enables a highly efficient and sustainable approach to the enantioselective alkylation of sulfonylimines via C(sp3)-H functionalization. In this protocol, anodic oxidation for benzylic radical formation and Lewis acid-catalyzed sulfonylimine reduction on the cathode were seamlessly cross-coupled (up to 88 % yield). Enantioenriched chiral amines containing a tetrasubstituted carbon stereocenter are accessed with high enantioselectivity (up to 96 % ee). Mechanistic studies suggest that the amine generated in situ could serve as a base to deprotonate phenols and decrease the oxidation potential of the reaction, allowing phenols with lower potentials to be preferentially oxidized.

The Story, Properties and Applications of Bioactive Glass “1d”: From Concept to Early Clinical Trials

Bioactive glasses in the CaO–MgO–Na2O–P2O5–SiO2–CaF2 system are highly promising materials for bone and dental restorative applications. Furthermore, if thermally treated, they can crystallize into diopside–fluorapatite–wollastonite glass-ceramics (GCs), which exhibit appealing properties in terms of mechanical behaviour and overall bone-regenerative potential. In this review, we describe and critically discuss the genesis, development, properties and applications of bioactive glass “1d” and its relevant GC derivative products, which can be considered a good example of success cases in this class of SiO2/CaO-based biocompatible materials. Bioactive glass 1d can be produced by melt-quenching in the form of powder or monolithic pieces, and was also used to prepare injectable pastes and three-dimensional porous scaffolds. Over the past 15 years, it was investigated by the authors of this article in a number of in vitro, in vivo (with animals) and clinical studies, proving to be a great option for hard tissue engineering applications.

Fabrication of 3D PCL/PVP scaffolds using monosodium glutamate as porogen by solvent casting/particulate leaching method for oral and maxillofacial bone tissue engineering

The design of three-dimensional (3D) scaffolds should focus on creating highly porous, 3D structures with an interconnected pore network that supports cell growth. The scaffold's pore interconnectivity is directly linked to vascularization, cell seeding, guided cell migration, and transportation of nutrients and metabolic waste. In this study, different types of food flavors including monosodium glutamate, sugar, and sodium chloride were used as the porogens along with PCL/PVP blend polymer for solvent casting/particulate leaching method. The morphology, porosity, interconnectivity, chemical composition, water absorption, and mechanical properties of the fabricated scaffolds are carefully characterized. The scaffolds are biocompatible in bothin vitroandin vivoexperiments and do not trigger any inflammatory response while enhancing new bone formation and vascularization in rabbit calvaria critical-sized defects. The new bone merges and becomes denser along with the experiment timeline. The results indicate that the 3D PCL/PVP scaffolds, using monosodium glutamate as porogen, exhibited suitable biological performance and held promise for bone tissue engineering in oral and maxillofacial surgery.

Fibronectin Functionalization: A Way to Enhance Dynamic Cell Culture on Alginate/Hydroxyapatite Scaffolds.

Bone defects are a global health concern; bone tissue engineering (BTE) is the most promising alternative to reduce patient morbidity and overcome the inherent drawbacks of autograft and allograft bone. Three-dimensional scaffolds are pivotal in this field due to their potential to provide structural support and mimic the natural bone microenvironment. Following an already published protocol, a 3D porous structure consisting of alginate and hydroxyapatite was prepared after a gelation step and a freezing-drying step. Despite the frequent use of alginate in tissue regeneration, the biological inertness of this polysaccharide hampers proper cell colonization and proliferation. Therefore, the purpose of this work was to enhance the biological properties by promoting the interaction and adhesion between cells and biomaterial with the use of Fibronectin. This extracellular matrix protein was physically adsorbed on the scaffold, and its presence was evaluated with environmental scanning electron microscopy (eSEM) and the Micro-Bicinchoninic Acid (μBCA) protein assay. The MG-63 cell line was used for both static and dynamic (i.e., in bioreactor) 3D cell culturing on the scaffolds. The use of the bioreactor allowed for a better exchange of nutrients and oxygen and a better removal of cell catabolites from the inner portion of the construct, mimicking the physiological environment. The functionalized scaffolds showed an improvement in cell proliferation and colonization compared to non-functionalized ones; the effect of the addition of Fibronectin was more evident in the dynamic culturing conditions, where the cells clearly adhered on the surface of functionalized scaffolds.

An Analysis of the Biocompatibility, Cytotoxicity, and Bone Conductivity of Polycaprolactone: An In Vivo Study.

Tissue engineering represents a promising field in regenerative medicine, with bioresorbable polymers such as polycaprolactone (PCL) playing a crucial role as scaffolds. These scaffolds support the growth and repair of tissues by mimicking the extracellular matrix. This study aimed to assess the in vivo performance of three-dimensional PCL scaffolds by evaluating their effects on bone repair in rat calvaria and the tissue reaction in subcutaneous implant sites, as well as their impact on major organs such as the kidneys, lungs, and liver. Three-dimensional scaffolds made of PCL were implanted in the subcutaneous tissue of rats' backs and calvaria. Histological analyses were conducted to observe the bone repair process in calvaria and the tissue response in subcutaneous implant sites. Additionally, the kidneys, lungs, and livers of the animals were examined for any adverse tissue alterations. The histological analysis of the bone repair in calvaria revealed newly formed bone growing towards the center of the defects. In subcutaneous tissues, a thin fibrous capsule with collagenous fibers enveloping the implant was observed in all animals, indicating a positive tissue response. Importantly, no harmful alterations or signs of inflammation, hyperplasia, metaplasia, dysplasia, or hemorrhage were detected in the kidneys, lungs, and liver. The findings demonstrate that PCL scaffolds produced through additive manufacturing are biocompatible, non-cytotoxic, and bioresorbable, promoting osteoconduction without adverse effects on major organs. Hence, PCL is confirmed as a suitable biomaterial for further studies in tissue engineering and regenerative medicine.

Three-dimensional porous polycaprolactone/chitosan/bioactive glass scaffold for bone tissue engineering

Three-dimensional (3D) porous scaffolds based on polycaprolactone (PCL)/chitosan (CS)/bioactive glass (BG) nanoparticle composites were fabricated by the freeze-drying technique for bone tissue engineering. The physiochemical properties of the developed PCL/CS/BG scaffolds were studied using FTIR, XRD, EDX and SEM. Furthermore, the swelling degree, porosity, water retention ability, compression strength, in vitro biodegradation, bioactivity and biocompatibility of the scaffolds were examined. The PCL/CS/BG scaffolds with 4 wt. % of BG content presented adequate pore size (106 μm), porosity (156%), water swelling degree (128%), water retention ability (179%), compressive strength (3.7 MPa) and controlled degradation behavior, which could be ideal for bone tissue engineering. The PCL/CS/BG composite scaffolds showed good antimicrobial activity against both test bacteria and fungi. The MTT assay demonstrated the biocompatibility of PCL/CS/BG scaffolds against C3H10T1/2 cell line. The Alizarin red staining assay confirmed the osteogenic activity of the PCL/CS/BG scaffolds.

(Invited) A Facile Three-Dimensional Lightweight Current Collector Strategy for High Energy Density Lithium Metal Batteries

Despite the great achievement in the development of rechargeable lithium (Li) metal batteries (LMBs) with high energy densities, their practical application is still facing difficulties due to the intrinsic issues of Li metal anode (LMA) including high reactivity and dendritic Li formation which cause low Coulombic efficiency, constant loss of Li and electrolyte, and unstable solid electrolyte interphase (SEI) layer, etc. Additionally, from the structural point of view, LMA which consists of Li foil on the two-dimensional copper (Cu) current collector brings the formidable loss of the areal capacity that leads to less specific energy density since Cu is non-faradaic and one of the heavy metals. Further, the “hostless” feature of LMA induces more issues like volume expansion and limited utilization of Li. To address such issues, a metal-coated polymeric three-dimensional (3D) scaffold is designed here. In this study, Cu is selected as an electronic conductivity provider, and electrospun polyimide (PI) is chosen as a 3D scaffold because of its high thermal stability and good mechanical properties. Cu-coated PI (Cu@PI) was produced via a facile electroless process. Driven by the structural/material uniqueness, the developed 3D Cu@PI current collector enables a uniform/continuous Li-ion conduction pathway thus leading to dense Li deposition and enhancing the electrochemical performance of LMBs containing the electrochemically deposited Li on Cu@PI and the specific energy density due to the great reduction in substrate weight. We anticipate the suggested new strategy of 3D structured LMAs would lead to a facile route toward the high energy density LMBs beyond the conventional technologies.

Single-Walled Carbon Nanotubes As Fluorescent Probes for Supramolecular Self-Assembly Complexes

Semiconducting single-walled carbon nanotubes (SWCNTs) are distinguished by their fluorescence in the near-infrared range, which overlaps with the transparency window of biological samples, and they do not photobleach or blink. Utilizing their unique optical properties, SWCNTs can be rendered optical probes for the characterization and analysis of bio-inspired peptide-based hydrogels. Peptide hydrogels, formed through the supramolecular self-assembly of conjugated amino acids, provide versatile three-dimensional scaffolds for applications in cell culture, tissue engineering, and regenerative medicine. The inherent properties of these amino acids or peptides, notably their limited solubility in water, drive them to self-assemble into elongated fibrillary nanostructures, ultimately creating self-supporting hydrogel matrices. We integrate near-infrared fluorescent SWCNTs into these peptide hydrogels as dynamic fluorescent probes, offering real-time insights into the morphological and structural evolution of the hydrogels. This approach not only enhances our understanding of the self-assembly mechanisms at play but also opens new avenues in supramolecular science. The integration of SWCNTs into the supramolecular structures showcases their potential as a powerful tool for long-term, non-invasive monitoring, with immense promise for numerous biomedical applications.

Preventing bacterial adhesion on scaffolds for bone tissue engineering

Bone implant infection constitutes a major sanitary concern which is associated to high morbidity and health costs. This manuscript focused on overviewing the main research efforts committed up to date to develop innovative alternatives to conventional treatments, such as those with antibiotics. These strategies mainly rely on chemical modifications of the surface of biomaterials, such as providing it of zwitterionic nature, and tailoring the nanostructure surface of metal implants. These surface modifications have successfully allowed inhibition of bacterial adhesion, which is the first step to implant infection, and preventing long-term biofilm formation compared to pristine materials. These strategies could be easily applied to provide three-dimensional (3D) scaffolds based on bioceramics and metals, of which its manufacture using rapid prototyping techniques was reviewed. This opens the gates for the design and development of advanced 3D scaffolds for bone tissue engineering to prevent bone implant infections.

Development and characterization of three-dimensional antibacterial nanocomposite sponges of chitosan, silver nanoparticles and halloysite nanotubes.

In this work, we developed novel nanocomposite three-dimensional (3D) scaffolds composed of chitosan (CTS), halloysite nanotubes (HNTs) and silver nanoparticles (AgNPs) with enhanced antimicrobial activity and fibroblast cell compatibility for their potential use in wound dressing applications. A stock CTS-HNT solution was obtained by mixing water-dispersed HNTs with CTS aqueous-acid solution, and then, AgNPs, in different concentrations, were synthesized in the CTS-HNT solution via a CTS-mediated in situ reduction method. Finally, freeze-gelation was used to obtain CTS-HNT-AgNP 3D porous scaffolds (sponges). Morphology analysis showed that synthesized AgNPs were spherical with an average diameter of 11 nm. HNTs' presence did not affect the AgNPs morphology or size but improved the mechanical properties of the scaffolds, where CTS-HNT sponges exhibited a 5 times larger compression stress than bare-CTS sponges. AgNPs in the scaffolds further increased their mechanical strength in correlation to the AgNP concentration, and conferred them improved antibacterial activity against Gram-negative and Gram-positive bacteria, inhibiting the planktonic proliferation and adhesion of bacteria in a AgNP concentration depending on manner. In vitro cell viability and immunofluorescence assays exhibited that human fibroblast (HF) culture was supported by the sponges, where HF retained their phenotype upon culture on the sponges. Present CTS-HNT-AgNP sponges showed promising mechanical, antibacterial and cytocompatibility properties to be used as potential scaffolds for wound dressing applications.

Cell Culture Models for Translational Research on Thymomas and Thymic Carcinomas: Current Status and Future Perspectives.

Cell culture model systems are fundamental tools for studying cancer biology and identifying therapeutic vulnerabilities in a controlled environment. TET cells are notoriously difficult to culture, with only a few permanent cell lines available. The optimal conditions and requirements for the ex vivo establishment and permanent expansion of TET cells have not been systematically studied, and it is currently unknown whether different TET subtypes require different culture conditions or specific supplements. The few permanent cell lines available represent only type AB thymomas and thymic carcinomas, while attempts to propagate tumor cells derived from type B thymomas so far have been frustrated. It is conceivable that epithelial cells in type B thymomas are critically dependent on their interaction with immature T cells or their three-dimensional scaffold. Extensive studies leading to validated cell culture protocols would be highly desirable and a major advance in the field. Alternative methods such as tumor cell organoid models, patient-derived xenografts, or tissue slices have been sporadically used in TETs, but their specific contributions and advantages remain to be shown.

In vitro investigations on the effects of graphene and graphene oxide on polycaprolactone bone tissue engineering scaffolds

Polycaprolactone (PCL) scaffolds that are produced through additive manufacturing are one of the most researched bone tissue engineering structures in the field. Due to the intrinsic limitations of PCL, carbon nanomaterials are often investigated to reinforce the PCL scaffolds. Despite several studies that have been conducted on carbon nanomaterials, such as graphene (G) and graphene oxide (GO), certain challenges remain in terms of the precise design of the biological and nonbiological properties of the scaffolds. This paper addresses this limitation by investigating both the nonbiological (element composition, surface, degradation, and thermal and mechanical properties) and biological characteristics of carbon nanomaterial-reinforced PCL scaffolds for bone tissue engineering applications. Results showed that the incorporation of G and GO increased surface properties (reduced modulus and wettability), material crystallinity, crystallization temperature, and degradation rate. However, the variations in compressive modulus, strength, surface hardness, and cell metabolic activity strongly depended on the type of reinforcement. Finally, a series of phenomenological models were developed based on experimental results to describe the variations of scaffold’s weight, fiber diameter, porosity, and mechanical properties as functions of degradation time and carbon nanomaterial concentrations. The results presented in this paper enable the design of three-dimensional (3D) bone scaffolds with tuned properties by adjusting the type and concentration of different functional fillers.Graphic abstract

Advances in Filament Structure of 3D Bioprinted Biodegradable Bone Repair Scaffolds.

Conventional bone repair scaffolds can no longer meet the high standards and requirements of clinical applications in terms of preparation process and service performance. Studies have shown that the diversity of filament structures of implantable scaffolds is closely related to their overall properties (mechanical properties, degradation properties, and biological properties). To better elucidate the characteristics and advantages of different filament structures, this paper retrieves and summarizes the state of the art in the filament structure of the three-dimensional (3D) bioprinted biodegradable bone repair scaffolds, mainly including single-layer structure, double-layer structure, hollow structure, core-shell structure and bionic structures. The eximious performance of the novel scaffolds was discussed from different aspects (material composition, ink configuration, printing parameters, etc.). Besides, the additional functions of the current bone repair scaffold, such as chondrogenesis, angiogenesis, anti-bacteria, and anti-tumor, were also concluded. Finally, the paper prospects the future material selection, structural design, functional development, and performance optimization of bone repair scaffolds.

In Vitro Biocompatibility Assessment of Bioengineered PLA-Hydrogel Core-Shell Scaffolds with Mesenchymal Stromal Cells for Bone Regeneration.

Human mesenchymal stromal cells (hMSCs), whether used alone or together with three-dimensional scaffolds, are the best-studied postnatal stem cells in regenerative medicine. In this study, innovative composite scaffolds consisting of a core-shell architecture were seeded with bone-marrow-derived hMSCs (BM-hMSCs) and tested for their biocompatibility and remarkable capacity to promote and support bone regeneration and mineralization. The scaffolds were prepared by grafting three different amounts of gelatin-chitosan (CH) hydrogel into a 3D-printed polylactic acid (PLA) core (PLA-CH), and the mechanical and degradation properties were analyzed. The BM-hMSCs were cultured in the scaffolds with the presence of growth medium (GM) or osteogenic medium (OM) with differentiation stimuli in combination with fetal bovine serum (FBS) or human platelet lysate (hPL). The primary objective was to determine the viability, proliferation, morphology, and spreading capacity of BM-hMSCs within the scaffolds, thereby confirming their biocompatibility. Secondly, the BM-hMSCs were shown to differentiate into osteoblasts and to facilitate scaffold mineralization. This was evinced by a positive Von Kossa result, the modulation of differentiation markers (osteocalcin and osteopontin), an expression of a marker of extracellular matrix remodeling (bone morphogenetic protein-2), and collagen I. The results of the energy-dispersive X-ray analysis (EDS) clearly demonstrate the presence of calcium and phosphorus in the samples that were incubated in OM, in the presence of FBS and hPL, but not in GM. The chemical distribution maps of calcium and phosphorus indicate that these elements are co-localized in the same areas of the sections, demonstrating the formation of hydroxyapatite. In conclusion, our findings show that the combination of BM-hMSCs and PLA-CH, regardless of the amount of hydrogel content, in the presence of differentiation stimuli, can provide a construct with enhanced osteogenicity for clinically relevant bone regeneration.

Porous gelatin-based phosphorylated scaffold: Microstructure, cell response and osteogenic differentiation of human adipose-derived mesenchymal stem cells

To repair the highly organized composite bone tissue, the design and development of biomimetic three-dimensional scaffolds is an active strategy. Here, we describe the fabrication route of a bioengineered gelatin-based scaffold for potential application in bone tissue engineering. First, phosphorus-containing polyurethane (PU–P) polymer was synthesized by polymerization starting from phosphorous polyol and methylene diisocyanate (DMI). Second, a gelatin/phosphorus-containing polyurethane (Gelatin/PU-P) scaffold was prepared by solution mixing, ultrasonication, and freeze-drying of gelatin and PU-P polymer. Next, prepared scaffold samples were characterized by FT-IR, SEM microscopy, porosity measurement, swelling, degradability, and mechanical tests. The scaffold with a porosity of about 78 % was achieved, and at the same time, it had good dimensional stability so that it only lost 43.61 % of its initial weight after 35 days immersing in PBS. Moreover, Gelatin/PU-P showed flexibility, large elongations at break (420 %) and high tensile strength (14 MPa). Finally, biological assessments revealed that the scaffold significantly supported the viability of Adipose-derived mesenchymal stem cells (ADMS). High ALP activity, enhancement in mineralization, and greater expression of osteogenic gene markers in cells grown on the Gelatin/PU-P confirmed the osteoinductivity of the scaffold. These findings suggested that Gelatin/PU-P can be used as a bioactive scaffold for bone tissue engineering.

Flexible and multi-functional three-dimensional scaffold based on enokitake-like Au nanowires for real-time monitoring of endothelial mechanotransduction

Endothelial cells are sensitive to mechanical force and can convert it into biochemical signals to trigger mechano-chemo-transduction. Although conventional techniques have been used to investigate the subsequent modifications of cellular expression after mechanical stimulation, the in situ and real-time acquiring the transient biochemical information during mechanotransduction process remains an enormous challenge. In this work, we develop a flexible and multi-functional three-dimensional conductive scaffold that integrates cell growth, mechanical stimulation, and electrochemical sensing by in situ growth of enokitake-like Au nanowires on a three-dimensional porous polydimethylsiloxane substrate. The conductive scaffold possesses stable and desirable electrochemical sensing performance toward nitric oxide under mechanical deformation. The prepared e-AuNWs/CC/PDMS scaffold exhibits a good electrocatalytic ability to NO with a linear range from 2.5 nM to 13.95 μM and a detection limit of 8 nM. Owing to the excellent cellular compatibility, endothelial cells can be cultured directly on the scaffold and the real-time inducing and recording of nitric oxide secretion under physiological and pathological conditions were achieved. This work renders a reliable sensing platform for real-time monitoring cytomechanical signaling during endothelial mechanotransduction and is expected to promote other related biological investigations based on three-dimensional cell culture.