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It remains a major challenge to develop a selective and effective fibrinolytic system for thrombolysis with minimal undesirable side effects. Herein, we report a multifunctional liposomal system (164.6 ± 5.3 nm in diameter) for selective thrombolysis through targeted delivery and controlled release of tissue plasminogen activator (tPA) at the thrombus site. The tPA-loaded liposomes were PEGylated to improve their stability, and surface coated with a conformationally-constrained, cyclic arginine-glycine-aspartic acid (cRGD) to enable highly selective binding to activated platelets. The in vitro drug release profiles at 37 o C showed that over 90% of tPA was released through liposomal membrane destabilization involving membrane fusion upon incubation with activated platelets within 1 h, whereas passive release of the encapsulated tPA in pH 7.4 PBS buffer was 10% after 6 h. The release of tPA could be readily manipulated by changing the concentration of activated platelets. The presence of activated platelets enabled the tPA-loaded, cRGD-coated, PEGylated liposomes to induce efficient fibrin clot lysis in a fibrin-agar plate model and the encapsulated tPA retained 97.4 ± 1.7% of fibrinolytic activity as compared with that of native tPA. Furthermore, almost complete blood clot lysis was achieved in 75 min, showing considerably higher and quicker thrombolytic activity compared to the tPA-loaded liposomes without cRGD labelling. These results suggest that the nano-sized, activated-platelet-sensitive, multifunctional liposomes could facilitate selective delivery and effective release of tPA at the site of thrombus, thus achieving efficient clot dissolution whilst minimising undesirable side effects.

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Clinical use of tissue plasminogen activator (tPA) in thrombolytic therapy is limited by its short circulation time and hemorrhagic side effects. Inspired by fibrinogen binding to activated platelets, we report a fibrinogen-mimicking, multiarm nanovesicle for thrombus-specific tPA delivery and targeted thrombolysis. This biomimetic system is based on the lipid nanovesicle coated with polyethylene glycol (PEG) terminally conjugated with a cyclic RGD (cRGD) peptide. Our experiments with human blood demonstrated its highly selective binding to activated platelets and efficient tPA release at a thrombus site under both static and physiological flow conditions. Its clot dissolution time in a microfluidic system was comparable to that of free tPA. Furthermore, we report a purpose-built computational model capable of simulating targeted thrombolysis of the tPA-loaded nanovesicle and with a potential in predicting the dynamics of thrombolysis in physiologically realistic scenarios. This combined experimental and computational work presents a promising platform for development of thrombolytic nanomedicines.

With the recent development of wearable electronics and smart textiles, flexible sensor technology is gaining increasing attention. Compared to flexible film‐based sensors, multimaterial fiber‐based technology offers unique advantages due to the breathability, durability, wear resistance, and stretchability in fabric structures. Despite the significant progress made in the fabrication and application of fiber‐based sensors, none of the existing fiber technologies allow for fully distributed pressure or temperature sensing. Herein, the design and fabrication of thermally drawn multi‐material fibers that offer distributed temperature and pressure measurement capability is reported. Thermoplastic materials, thermoplastic elastomers, and metal electrodes are successfully co‐drawn in one fiber. The embedded electrodes inside the fibers form a parallel wire transmission line, and the local characteristic impedance is designed to change with the temperature or pressure. The electrical frequency domain reflectometry is used to interrogate the impedance change along the fiber and provides information with high spatial resolution. The two types of fibers reported in this manuscript have a pressure sensitivity of 4 kPa and a temperature sensitivity of 2 °C, respectively. This work can pave the road for development of functional fibers and textiles for pressure and temperature mapping.

Highly stretchable fiber sensors have attracted significant interest recently due to their applications in wearable electronics, human–machine interfaces, and biomedical implantable devices. Here, a scalable approach for fabricating stretchable multifunctional electrical and optical fiber sensors using a thermal drawing process is reported. The fiber sensors can sustain at least 580% strain and up to 750% strain with a helix structure. The electrical fiber sensor simultaneously exhibits ultrahigh stretchability (400%), high gauge factors (≈1960), and excellent durability during 1000 stretching and bending cycles. It is also shown that the stretchable step‐index optical fibers facilitate detection of bending and stretching deformation through changes in the light transmission. By combining both electrical and optical detection schemes, multifunctional fibers can be used for quantifying and distinguishing multimodal deformations such as bending and stretching. The fibers’ utility and functionality in sensing and control applications are demonstrated in a smart glove for controlling a virtual hand model, a wrist brace for wrist motion tracking, fiber meshes for strain mapping, and real‐time monitoring of multiaxial expansion and shrinkage of porcine bladders. These results demonstrate that the fiber sensors can be promising candidates for smart textiles, robotics, prosthetics, and biomedical implantable devices.

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