However, the reported stretchable sensors work in 2D planar form, and the very few 3D scaffolds based on graphene and conducting polymer have great difficulty in withstanding large mechanical deformation for lack of elasticity. Recently, stretchable electrochemical sensors have emerged and demonstrated an enormous advantage for real-time inducing and monitoring of cell mechanotransduction with cells cultured thereon. Electrochemical sensing is a well-accepted forceful technique capable of real-time monitoring of chemical molecules from living cells or tissues with fast response and excellent sensitivity. To solve this problem, it will be a convincingly preferred approach to develop 3D scaffolds that could integrate with functions of cell culture, mechanical stimulation, and real-time detection capability, but no such a scaffold has been reported so far. Nevertheless, what appears to be missing in the exciting advances is techniques for real-time acquiring the dynamic information during cell mechanotransduction, since mechanical signals could trigger rapid biochemical responses within a second. Generally, the cellular responses to mechanical loading were investigated by characterizing cell morphology, marker proteins and gene levels, and such evidences were reported by the immunostaining, western blot, and polymerase chain reaction, after cells were subjected to mechanical stimulation for several hours or even days. In this regard, 3D scaffolds (e.g., collagen hydrogels, fibrin matrix, and polyurethane porous scaffold ) with deformable properties were used as the support to culture and investigate these cells under mechanical loading including tensile strain, shear stress, and compression. Mechanical loads are especially representative for resident cells in tissues such as ligament, bone, heart, muscle and so on, and these cells can sense and translate mechanical signals into biochemical responses via sophisticated mechanotransduction process. įor 3D cell culture, besides the “closer-to-in vivo” architectures and physical cues provided by scaffolds, mechanical loading has attracted increasing attention in recent years as its critical role on cell functions such as migration, growth, differentiation, and survival. Therefore, research focus has long centered on 3D scaffolds fabrication based on various materials (e.g., hydrogels of naturally derived protein or proteoglycan, synthetic polymers, and composite materials) and techniques (e.g., electrospinning and 3D printing). Among them, scaffolds-based 3D cell culture for cell adhesion, proliferation, and extracellular matrix production has attracted extensive attention, due to the effective nutrient transport, similar structures to native extracellular matrix, and tunable mechanical properties. Over the past decades, to better mimic such physiological conditions in vivo, 3D cell culture systems have emerged and greatly boosted the development of many fields such as tissue regeneration, pathophysiological study, and drug screening. This indicates the promising potential of the stretchable 3D sensing in exploring the mechanotransduction in 3D cellular systems and engineered tissues.Ĭells in vivo reside in a three-dimensional (3D) dynamic microenvironment consisting of soluble factors, cell-matrix interactions, cell–cell contacts, and specific physicochemical properties. The results disclose a previously unclear mechanotransduction pathway in chondrocytes that mechanical loading can rapidly activate nitric oxide signaling within seconds. This allows mimicking the articular cartilage and investigating its mechanotransduction by 3D culture, mechanical stretching of chondrocytes, and synchronously real-time monitoring of stretch-induced signaling molecules. The 3D scaffold demonstrates very good compatibility, excellent stretchability, and stable electrochemical sensing performance. Herein, for the first time, a stretchable and multifunctional platform integrating 3D cell culture, mechanical loading, and electrochemical sensing is developed by immobilization of biomimetic peptide linked gold nanotubes on porous and elastic polydimethylsiloxane. Mechanical loading is one of the critical factors that affect cell/tissue behaviors and metabolic activities, but the reported models or detection methods offer little direct and real-time information about mechanically induced cell responses. In the field of three-dimensional (3D) cell culture and tissue engineering, great advance focusing on functionalized materials and desirable culture systems has been made to mimic the natural environment of cells in vivo.
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