Connective tissue is a factor of great importance in tissue engineering and regenerative medicine because it has a limited life but complicated mechanical properties. In this study, we present a reinforcement method of hydrogel using patterned nanofibers to mimic native connective tissues with selective engagement of load carrying constituents. We incorporated a three-dimensional nanofibrous frame fabricated using direct-write electrospinning with a hydrogel matrix. Three types of nanofiber-reinforced hydrogel composite were fabricated and their dual aspects of mechanical properties for compressive load were identified. It was demonstrated that the constructed composite had sufficient biocompatibility as well as connective tissue-like mechanical properties.
Systemic administration of the immunosuppressive drug cyclosporin A (CsA) is frequently associated with a number of side effects; therefore, sometimes it cannot be applied in sufficient dosage after allogeneic or xenogeneic cell transplantation. Local delivery is a possible solution to this problem. We used 3D printing to develop a CsA-loaded 3D drug carrier for the purpose of local and sustained delivery of CsA. The carrier is a hybrid of CsA-poly(lactic-co-glycolic acid) (PLGA) microsphere-loaded hydrogel and a polymeric framework so that external force can be endured under physiological conditions. The expression of cytokines, which are secreted by spleen cells activated by Con A, and which are related to immune rejection, was significantly decreased in vitro by the released CsA from the drug carrier. Drug carriers seeded with xenogeneic cells (human lung fibroblast) were subcutaneously implanted into the BALB/c mouse. As a result, T-cell-mediated rejection was also significantly suppressed for 4 weeks. These results show that the developed 3D drug carrier can be used as an effective xenogeneic cell delivery system with controllable immunosuppressive drugs for cell-based therapy.
In this study, a subminiature implantable capacitive pressure sensor is proposed for biomedical applications. The proposed pressure sensor comprises an array of elastic silicon nitride (SiN) diaphragms formed by the application of a polysilicon (p-Si) sacrificial layer. In addition, using the p-Si layer, a resistive temperature sensor is also integrated into one device without additional fabrication steps or extra cost, thus enabling the device to measure pressure and temperature simultaneously. The sensor with a size of 0.5 × 1.2 mm was fabricated using microelectromechanical systems (MEMS) technology and was packaged in needle-shaped metal housing that is both insertable and biocompatible. The packaged pressure sensor immersed in a physiological saline solution exhibited excellent performance without leakage. The sensor achieved a sensitivity of approximately 1.73 pF/bar and a hysteresis of about 1.7%, respectively. Furthermore, it was confirmed that the pressure sensor operated normally for 48 h without experiencing insulation breakdown or degradation of the capacitance. The integrated resistive temperature sensor also worked properly. The response of the temperature sensor varied linearly with temperature variation. It had an acceptable temperature coefficient of resistance (TCR) of approximately 0.25%/°C.
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