Injectable, Drug-coated Microparticles for Regenerating Bone Tissue

Large-scale injuries to bone tissue can have many causes, including traumatic injury, birth defects, or as a side effect for cancer treatment. In particular, bone defects greater than 2cm in length are termed “critically-sized” since they often cannot heal spontaneously. These large  bone injuries are often treated with autologous bone grafts, or bone tissue harvested from the patient’s own body, though these procedures are limited by donor site morbidity and a limited amount of harvestable bone. To overcome these shortcomings seen with bone grafts, our lab is seeking to develop synthetic, “off-the-shelf” systems to regenerate these large bone injuries. We are currently developing an injectable drug delivery system made from coated microparticles that can release multiple therapies in sequence to promote the growth of new blood vessels and new bone tissue. The ~10µm particles, made from the polymer poly(propylene sulfide) (PPS), can be loaded with bone-regenerating drugs during fabrication but are small enough to be injected from a syringe. These particles can also be coated with a separate vessel-regenerating drug (Figure 1A). Importantly, both the drug coating and drug-loaded particles are selectively degraded by cell-generated reactive oxygen species (ROS). This allows for sequential drug release from the injected microparticles after triggering by the local cells at the bone injury site (Figure 1B-D).

For this proposed project, the Protégé Scholar will be heavily involved in the development of these coated microparticles. The Protégé Scholar will assist in optimizing the particle coating process, measuring drug release kinetics, and evaluating the biological response of this system in preparation for future pre-clinical testing in more complex biological models