This proposal addresses several existing challenges in developing better control systems for therapeutic tissue engineering including: 1) minimizing infection associated with delivered biomaterials/devices; 2) creating in-situ curable material with a suitable environment for local cell migration, stable cell delivery and promotion of injury repair; 3) establishing a stable adhesive interface between a tissue engineered construct (hydrogel) and injured tissues; 4) targeting spatial and temporal release of multifunctional dose dependent reactive oxygen species (ROS). The ROS releasing composite adhesive-hydrogels and focused ultrasound (FUS) delivery system being developed in this proposal addresses these challenges. The primary innovative component is the possible use of FUS to spatially and temporally target ROS release as a regenerative tissue support that not only aids in stabilizing the matrix metabolic activity of the regenerative site but also provides secondary support through its innate antimicrobial character. The main objectives of this proposal are: 1) create a library of composite hydrogel formulations with controlled ROS release profiles as well as physical and adhesive properties; 2) build a custom FUS therapy system and characterize its ability modulate formulations in real-time to target wound healing and prevent infection in vitro; 3) verify candidate formulations promote wound healing in an Achilles tendon defect model.
To date a therapy does not exist to control the wound healing and antimicrobial activity of reactive oxygen species in real-time. The use of novel materials in this proposal combined with focused ultrasound (FUS) may provide the means to achieve this temporal and spatial control for use in the healing of tendon injury. The potential advantage of this system is that it could allow for the direct and localized delivery of agents that provide antimicrobial activity independent of antibiotics, and promote stable wound healing.
