Directing cellular functionalities using biomaterial-based bioelectronic stimulation remains a significant constraint in translating research outcomes to address specific clinical needs. Electrical stimulation is now being clinically used as a therapeutic treatment option to promote bone tissue regeneration and to improve neuromuscular functionalities. However, the nature of the electrical waveforms during the stimulation and underlying biophysical rationale are still not scientifically well explored. Furthermore, bone-mimicking implant-based bioelectrical regulation of osteoinductivity has not been translated to clinics. The present study demonstrates the role of the electrical stimulation waveform to direct differentiation of stem cells on an electroactive polymeric substrate, using monophasic direct current (DC), square waveform, and biphasic waveform. In this regard, an in-house electrical stimulation device has been fabricated for the uninterrupted delivery of programmed electrical signals to stem cells in culture. To provide a functional platform for stem cells to differentiate, barium titanate (BaTiO 3 , BT) reinforced poly (vinylidene difluoride) (PVDF) has been developed with mechanical properties similar to bone. The electrical stimulation of human mesenchymal stem cells (hMSCs) on PVDF/BT composite inhibited proliferation rate at day 7, indicating early commitment for differentiation. The phenotypical characteristics of DC stimulated hMSCs provided signatures of differentiation towards osteogenic lineage, which was subsequently confirmed using alkaline phosphatase assay, collagen deposition, matrix mineralization, and genetic expression. Our findings suggest that DC stimulation induced early osteogenesis in hMSCs with a higher level of intracellular reactive oxygen species (ROS), whereas the stimulation with square wave directed late osteogenesis with a lower ROS regeneration. In summary, the present study critically analyzes the role of electrical stimulation waveforms in regulating osteogenesis, without external biochemical differentiation inducers, on a bonemimicking functional biomaterial substrate. Such a strategy can potentially be adopted to develop orthopedic implant-based bioelectronic medicine for bone regeneration.
Stenosis reduces the effective lumen area in the tracheal and bronchial segments of the airway anatomy. Loss in patency due to obstruction increases resistance to airflow; thus, severe narrowing is often associated with morbidity and mortality. Etiologies such as congenital tracheal stenosis, tracheomalacia, laryngeal and subglottic stenosis, atresia are few among the many pathologies causing major airway obstruction and respiratory distress. Diagnosis of such anomalies is usually based on clinical suspicion due to the non-specificity of the associated clinical symptoms. Visual assessment using conventional bronchoscopy or radiography images from CT scan for precisely locating obstruction site is highly subject to clinician's expertise. Characterizing airflow patterns in stenosed airway calls for newer diagnostic tools that can effectively quantify changes in airflow due to construction sites. Our work presents a steerable intubation catheter that can quantitatively measure air velocity across various segments of the tracheobronchial tree. The catheter consists of a three-layer flexible printed circuit board integrated with micro-electro-mechanical system-based thermal flow sensors and a pair of sub-millimeter helical shape memory actuators. Flow distribution is measured in excised sheep tracheal tissues at 15, 30, 50, 65, and 80 l min −1 for normal and stenosed conditions. Even a 10% reduction in lumen area generated unique peaks corresponding to the obstruction site; thus, the catheter can locate stenosis at the precritical stage. For 50% tracheal obliteration, the sensor closest to stenosis showed a 2.4-fold increase in velocity when tested for reciprocating flows. Thus, flow rate scales quadratically with reducing cross-section area, contributing to increased airflow resistance.
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