This research seeks to investigate a controlled, sustained delivery system for two different types of bioactive factors that could aid in the repair of injured growth plates in children. If the cartilage tissue in the growth plate is injured, bony tissue is deposited at the injured site, thus disrupting the growth plate and leading to abnormal bone growth. A new biomaterial delivery system that provides local, sustained delivery of silencing RNA and TGF-1 growth factor will be engineered, and the influence of the co-delivery of these bioactive factors on the chondrogenic differentiation of mesenchymal stem cells examined. Short interfering RNA (siRNA) provides a powerful gene silencing mechanism, inhibiting gene expression at the translational level by targeted destruction of specific mRNA sequences. Due to this ability to silence the expression of specific proteins, and since siRNA functions directly in the cytoplasm of the cell rather than being incorporated into the genomic DNA and its effect is transient, the impact of siRNA in clinical applications could be enormous. Unfortunately, the delivery of siRNA is currently a major hurdle to its clinical use, as siRNA is readily degraded and cleared from the body. The work in this proposal will provide new methods for delivering siRNA to a local site in a sustained, controlled manner. Co-delivery of growth factor to improve cartilage repair of growth plate injuries will also be examined. Thus, the engineering solution proposed here is the development of a delivery system capable of releasing two different bioactive factors, one to inhibit the formation of the bony tissue at the injury site and another to encourage the chondrogenic differentiation of stem cells that are present in the area so they form cartilage tissue.
Broader Significance and Importance:
Ultimately this technology could offer a much-needed therapeutic option for growth plate injuries in children. As children grow, their bones lengthen by mineralization of cartilage at the bone-cartilage interface in the growth plate. Injury to the growth plate can lead to the deposition of bony tissue within the cartilage, thus disrupting the growth plate. This disruption can result in serious consequences, including the bone not growing to its full length or the growth occurring abnormally such that the bone curves as it grows. In addition to addressing a clear clinical need, the results of the proposed work will provide new methods for localized and sustained delivery of silencing RNA, which could potentially benefit other applications in the future as well.
Broader Impacts:
This award will support both the increase and continuation of outreach efforts by Professor Krebs's lab. It will directly support the training of one graduate student for 2 years and the involvement of at least one undergraduate student and one high school intern in the project. The PI and graduate student will be participating in a summer camp for K-6 dyslexic students, designing science modules that will be presented to the students over the course of 2 of the 5 weeks of the summer camp. This will have a substantial impact on the students at the camp in awakening their scientific interest, and also on the PI and graduate student in learning more about dyslexia and ways that individuals can overcome it and/or use it to their benefit. The PI will also continue her support of hosting 1-2 female high school interns in the lab during the academic year through internship programs of local high schools. These students will work side-by-side with a graduate student and the PI on a specific project, and see it develop over the course of the year. Finally, the project would have broad societal impacts by providing a new biomaterial delivery system that could improve the treatment of growth plate injuries and also be used for other tissue regeneration applications in the future.
This research has been funded through the Broadening Participation Research Initiation Grants in Engineering solicitation, which is part of the Broadening Participation in Engineering Program of the Engineering Education and Centers Division.
