Electrical, Computer, and Biomedical Engineering
Tissue Engineering; Hydrogel; Sequential Release
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In 2012, approximately 6.8 million people in the United States were diagnosed with orthopedic injuries or diseases. Over 500,000 people in the United States underwent bone grafting procedures, which cost 2.5 billion dollars per year and can result in complications. Polymer-based grafting scaffolds can facilitate 3D bone tissue growth in a localized, sustained manner. However, bone regeneration requires the orchestration of a sequence of events. Current scaffolds based on degradation and diffusion cannot provide sequential deliveries. We aimed to design a polymer scaffold that can release one payload diffusively at early time points, followed by ultrasonically triggered release of a second payload. The ability to deliver sequential payloads on demand (using ultrasonic stimulation) can more accurately mimic natural biological responses. Calcium alginate hydrogels were loaded with model drugs (fluorescently labeled dextrans of various charges and sizes) in order to characterize drug release due to diffusion, compared to when stimulated by different ultrasonic signals. Dextran release was quantitatively measured on a plate reader against a standard curve by measuring fluorescence at 525 nm. These studies uncovered optimal ultrasonic stimulation parameters (20 kHz signal for 3 minutes at 20% amplitude) that resulted in statistically significant drug release compared to controls while (i) preserving the 3D structure of the hydrogel scaffold and (ii) minimizing rises in temperatures to maintain the bio-activity of bio-molecular payloads. Furthermore, these studies identified trends of uncharged drugs diffusing out of the scaffold prior to stimulation while small, charged drugs being retained and ultrasonically released in an on-demand manner.