Design evolution enhances patient compliance for low-intensity pulsed ultrasound device usage

Neill M Pounder, John T Jones, Kevin J Tanis Bioventus LLC, Durham, NC, USA Abstract: Poor patient compliance or nonadherence with prescribed treatments can have a significant unfavorable impact on medical costs and clinical outcomes. In the current study, voice-of-the-customer research was conducted to aid in the development of a next-generation low-intensity pulsed ultrasound (LIPUS) bone healing product. An opportunity to improve patient compliance reporting was identified, resulting in the incorporation into the next-generation device of a visual calendar that provides direct feedback to the patient, indicating days for which they successfully completed treatment. Further ­investigation was done on whether inclusion of the visual calendar improved patient adherence to the prescribed therapy (20 minutes of daily treatment) over a 6-month period. Thus, 12,984 data files were analyzed from patients prescribed either the earlier- or the next-generation LIPUS device. Over the 6-month period, overall patient compliance was 83.8% with the next-generation LIPUS device, compared with 74.2% for the previous version (p<0.0001). Incorporation of the calendar feature resulted in compliance never decreasing below 76% over the analysis period, whereas compliance with the earlier-generation product fell to 51%. A literature review on the LIPUS device shows a correlation between clinical effectiveness and compliance rates more than 70%. Incorporation of stakeholder feedback throughout the design and innovation process of a next-generation LIPUS device resulted in a measurable improvement in patient adherence, which may help to optimize clinical outcomes. Keywords: LIPUS, ultrasound, compliance, patient adherence, medical device desig

Improved human bone marrow mesenchymal stem cell osteogenesis in 3D bioprinted tissue scaffolds with low intensity pulsed ultrasound stimulation

3D printing and ultrasound techniques are showing great promise in the evolution of human musculoskeletal tissue repair and regeneration medicine. The uniqueness of the present study was to combine low intensity pulsed ultrasound (LIPUS) and advanced 3D printing techniques to synergistically improve growth and osteogenic differentiation of human mesenchymal stem cells (MSC). Specifically, polyethylene glycol diacrylate bioinks containing cell adhesive Arginine-Glycine-Aspartic acid-Serene (RGDS) peptide and/or nanocrystalline hydroxyapatite (nHA) were used to fabricate 3D scaffolds with different geometric patterns via novel table-top stereolithography 3D printer. The resultant scaffolds provide a highly porous and interconnected 3D environment to support cell proliferation. Scaffolds with small square pores were determined to be the optimal geometric pattern for MSC attachment and growth. The optimal LIPUS working parameters were determined to be 1.5 MHz, 20% duty cycle with 150 mW/cm2 intensity. Results demonstrated that RGDS peptide and nHA containing 3D printed scaffolds under LIPUS treatment can greatly promote MSC proliferation, alkaline phosphatase activity, calcium deposition and total protein content. These results illustrate the effectiveness of the combination of LIPUS and biomimetic 3D printing scaffolds as a valuable combinatorial tool for improved MSC function, thus make them promising for future clinical and various regenerative medicine application. © The Author(s) 2016