RESUMEN
Background: Digital adherence technologies hold promise to improve patient-centered tuberculosis (TB) monitoring, yet few studies have incorporated direct adherence monitoring or assessed patients' experiences with these technologies. We explored acceptability, feasibility, and refinement needs of the TB Treatment Support Tools (TB-TSTs) intervention linking a mobile app, a urine drug metabolite test, and interactive communication with a treatment supporter. Methods: This pilot study was a parallel-designed single-center randomized controlled trial with exit interviews. Newly diagnosed TB patients were randomized 1:1 using a treatment allocation button in the REDCap software preloaded with a random allocation sequence to usual care or usual care plus the TB-TSTs intervention from a respiratory medicine hospital in the province of Buenos Aires, Argentina and followed for 6-months. Due to the nature of the intervention, blinding to the group allocation could not be achieved for the recruiter or patients. The treatment outcome data extractor was blinded to the group allocation of the participants. Intervention participants used the app to report self-administering medication, potential side effects, submit photos of the urine test, and interact with a treatment supporter. Outcomes were feasibility, acceptability, and treatment outcomes. Findings: Forty-two patients were enrolled and evenly assigned to each group. Intervention participants submitted 147·2±58 (mean, SD) medication self-administration and 144·5±55 side effect reports out of 180 and 47.5±38·4 photos of the urine test out of 77. Treatment success for usual care was 81% [17/21] and 95% [20/21] for the TB-TSTs intervention. Thirty-three themes were identified within the main categories of motivation, what worked, issues experienced, and recommendations. Participants (n=12) rated it as 'easy to use' (4.57/5), 'would highly recommend to others' (4·43/5) and reported that access to the treatment support was a critical component. Recommendations included adding an alarm, appointment reminders, and off-line functionality. Interpretation: Findings suggest that the TB-TSTs intervention was feasible and acceptable and further refinement and testing is warranted. Funding: National Institute of Health K23NR017210.
RESUMEN
Tissue engineering aims to capture the structural and functional aspects of diverse tissue types in vitro. However, most approaches are limited in their ability to produce complex 3D geometries that are essential for tissue function. Tissues, such as the vasculature or chambers of the heart, often possess curved surfaces and hollow lumens that are difficult to recapitulate given their anisotropic architecture. Cell-sheet engineering techniques using thermoresponsive substrates provide a means to stack individual layers of cells with spatial control to create dense, scaffold-free tissues. In this study, we developed a novel method to fabricate complex 3D structures by layering multiple sheets of aligned cells onto flexible scaffolds and casting them into hollow tubular geometries using custom molds and gelatin hydrogels. To enable the fabrication of 3D tissues, we adapted our previously developed thermoresponsive nanopatterned cell-sheet technology by applying it to flexible substrates that could be folded as a form of tissue origami. We demonstrated the versatile nature of this platform by casting aligned sheets of smooth and cardiac muscle cells circumferentially around the surfaces of gelatin hydrogel tubes with hollow lumens. Additionally, we patterned skeletal muscle in the same fashion to recapitulate the 3D curvature that is observed in the muscles of the trunk. The circumferential cell patterning in each case was maintained after one week in culture and even encouraged organized skeletal myotube formation. Additionally, with the application of electrical field stimulation, skeletal myotubes began to assemble functional sarcomeres that could contract. Cardiac tubes could spontaneously contract and be paced for up to one month. Our flexible cell-sheet engineering approach provides an adaptable method to recapitulate more complex 3D geometries with tissue specific customization through the addition of different cell types, mold shapes, and hydrogels. By enabling the fabrication of scaled biomimetic models of human tissues, this approach could potentially be used to investigate tissue structure-function relationships, development, and maturation in the dish.
