The main goal of this proposal is to develop a highly integrated research, education, and outreach program around the development of bioactive hybrid nanomatrices for intervertebral disk (IVD) regeneration. The proposed work is an interdisciplinary project that integrates nanotechnology, materials sciences, stem cell biology, and tissue engineering. Low back pain is one of the leading causes of disability and mainly caused by the degeneration of IVD. Current treatment options are limited because they can ease the pain but are unable to completely restore normal functions or promote new tissue regeneration. Thus, this CAREER proposal is transformative because it provides an innovative strategy to regenerate IVD by tackling the current challenges of electrospun nanofibers and self-assembled peptide amphiphiles (PAs) along with promoting multi levels of education and outreach programs. Electrospinning has gained lots of attention for various biomedical applications. However, the current major challenges facing electrospun nanofiber scaffolds include the lack of bioactivity on the nanofiber surface and the difficulties involved in trying to fabricate porous three dimensional structures. Endowed bioactivity is needed to control the cellular response to the biomaterial. The fabrication of a porous three dimensional electrospun scaffold is vital for cell encapsulation and infiltration because the current electrospun scaffolds are limited by their dense sheet structure. The proposed strategy is designed to overcome both of these challenges by developing bioactive hybrid nanomatrices that combine the unique characteristics of electrospun poly(Ã¥-caprolactone) (PCL) nanofibers and self-assembled peptide amphiphiles (PAs). The preliminary studies conducted strongly support our hypothesis. In particular, the self-assembled PAs can endow electrospun PCL nanofibers with bioactive properties, and a novel method is under development to fabricate electrospun PCL nanofibers into three dimensional porous structures. Therefore, the intellectual merit of this proposal is to provide fundamental insight into designing nanostructured, IVD mimicking scaffolds by combining electrospun nanofibers and self-assembled PAs. These bioactive hybrid nanomatrices are expected to overcome the current challenges of both electrospun nanofibers and PAs along with using their unique advantages. The electrospun PCL nanofibers will be coated with self-assembled PAs, thus endowing the PCL nanofibers with bioactive properties. These bioactive hybrid nanofibers will be characterized, and optimal coating conditions will be determined. Furthermore, the electrospun PCL nanofibers will be fabricated into a porous three dimensional structure using the newly developed method and then embedded in self-assembled PA gels to create bioactive hybrid nanomatrices. These nanomatrices will provide encapsulated human mesenchymal stem cells (hMSCs) with an ideal IVD mimicking environment via characteristic cell adhesive ligands and tunable mechanical properties. Cellular responses to these different environments will be evaluated in order to develop a comprehensive strategy for IVD regeneration The proposed research will also have the broad impact across multiple levels of education and outreach programs (graduate, undergraduate, high, and middle school): a. thesis based research activities for graduate and undergraduate students in nanostructured biomaterials and stem cell based tissue regeneration; b. development of a new interdisciplinary curriculum by combining lectures and hands-on laboratory activities; c. development of two new community outreach programs for the promotion of leadership and career opportunities for women and underrepresented minorities in middle school and high school; d. development of a new outreach program targeting students with disabilities, and e. development of industrial and international partnership for improving multidisciplinary training and collaboration skills.
