In vitro cell culture models for ultrasound treatments using collagen-based scaffolds.

Applications involving ultrasound treatment as a therapeutic strategy have gained interest due to its enhanced tissue penetration, broad availability, and minimal invasiveness. Recently, ultrasound treatment has been utilized for applications such as controlled drug delivery, enhanced drug penetration, sonodynamic therapy for generating ROS species, and targeted tissue ablation. However, our ability to study and explore applications is limited by the lack of in vitro models that enable efficient and representative screening of ultrasound-based therapeutic strategies. There is a need for cell culture approaches that mimic the mechanical environment of native tissues, which can prevent uncontrolled cell lysis due to ultrasonic energy. We developed two-dimensional and three-dimensional collagen-based materials for culturing cells in vitro that withstand ultrasound treatment. We hypothesized that the collagen matrix mimics the extracellular matrix and absorb most of the energy from ultrasound treatment - similar to in vivo effects - thereby preventing uncontrolled cell lysis. In this study, we developed a strategy for fabricating both the 2D coatings and 3D hydrogels coatings and tested the viability of the cultured cells post different durations of ultrasound treatment.

Ultrasound-Enhanced Antibacterial Activity of Polymeric Nanoparticles for Eradicating Bacterial Biofilms.

Bacterial biofilms are a major healthcare concern resulting in refractory conditions such as chronic wounds, implant infections and failure, and multidrug-resistant infections. Aggressive and invasive strategies are employed to cure biofilm infections but are prone to long and expensive treatments, adverse side-effects, and low patient compliance. Recent strategies such as ultrasound-based therapies and antimicrobial nanomaterials have shown some promise in the effective eradication of biofilms. However, maximizing therapeutic effect while minimizing healthy tissue damage is a key challenge that needs to be addressed. Here a combination treatment involving ultrasound and antimicrobial polymeric nanoparticles (PNPs) that synergistically eradicate bacterial biofilms is reported. Ultrasound treatment rapidly disrupts biofilms and increases penetration of antimicrobial PNPs thereby enhancing their antimicrobial activity. This results in superior biofilm toxicity, while allowing for a two- to sixfold reduction in both the concentration of PNPs as well as the duration of ultrasound. Furthermore, that this reduction minimizes cytotoxicity toward fibroblast cells, while resulting in a 100- to 1000-fold reduction in bacterial concentration, is demonstrated.